research limitations due to covid 19

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Areas of academic research with the impact of COVID-19

Abid haleem.

a Department of Mechanical Engineering, Jamia Millia Islamia, New Delhi, India

Mohd Javaid

Raju vaishya.

b Department of Orthopaedics, Indraprastha Apollo Hospital, Sarita Vihar, Mathura Road, 110076 New Delhi, India

S.G. Deshmukh

c Department of Mechanical Engineering, Indian Institute of Technology Delhi, New Delhi, India

Coronavirus (COVID-19) endemic is growing exponentially in the whole world. Researchers, technologists, doctors and other healthcare workers are working day and night on the development of vaccine and medicinesto control and treat this virus. SARS-CoV-2 is the name of the virus responsible for causing COVID-19 disease, which is highly infectious and lethal.With exponentially increasing infections, proportionate fatalities are being reported both from developed and under developed countries. As of today, more than one million people across the world have been reported infected with this virus, and more than 65,000 people have died of this disease. Hence, there is an urgent requirement for conducting academic research on several aspects of this highly contagious disease, to find effective means of containment and treatment of the disease, for now, and in future. We have identified some opportunities for academic research related to COVID-19 and have also provided suggestions to contain, prevent and treat this viral infection.

The SARS-CoV-2 virus has significantly affected the health, economy, and socio-economic fabric of the global society. The costs involved in the containment and treatment of this infectious disease are exorbitantly high, which even the wealthiestand developed countries are finding it difficult to sustain. COVID-19 pandemic has severely impacted the crude, stock market, gold and metals and almost all areas of the global market [ 1 ]. Large research laboratories and corporate houses are working with a high speed to develop medicines and vaccines for the prevention and treatment of this dreaded disease. To deal with these current health management challenges, we need a comprehensive understanding of the effect on the health system, global business, and culture. COVID-19 was declared a pandemic by the WHO on 11th March 2020 [ 2 ]. COVID-19 has become an international emergency in a short period and will have long-lasting effects. There is an urgent need to identify and study the areas of academic research which will be impacted by COVID-19 [ 3 ].

1. Research objectives

This manuscript highlights potential areas of academic research which are likely to be impacted by COVID-19. The main objectives of this paper are to provide awareness and to identify the research areas related to COVID-19. It may help improve the understanding of this disease and describe the psychological impacts of this pandemic and how these could change as the disease spreads.

2. Current limitations and gaps in the knowledge of Coronavirus and its effects

It appears the Coronavirus is zoonotic and originated in China. Scientists have not yet been able to identify the animal source of the infectious agent and have not determined whether a persistent animal reservoir of the infectious agent exists. It is also unclear whether SARS, like influenza, is a seasonal disease that would have receded on its own. It remains to be seen whether it will reemerge on a seasonal basis, and if so, how virulent future manifestations would be. The answers to these questions would undoubtedly advance the world's ability to predict and prepare for a resurgence of COVID-19.

3. Significant research areas on COVID-19

COVID-19 has disrupted the economies and the lives of individuals around the world. There are many areas of research needed regarding COVID-19 [ [4] , [5] , [6] ]. Table 1 identifies significant research areas which be profoundly impacted by this pandemic. We need to undertake extensive research on these areas.

Major research areas which will be impacted by COVID-19.

Extensive research is required for the development of a vaccine for the prevention of Coronavirus infection. There is an urgent need for early production and manufacturing of the essential items like personal protective equipment, medicines, and ventilators to combat this pandemic. All measures to keep a social distancing by the public must be ensured by avoiding social-cultural and religious programs and festivals etc. during this pandemic. Along with these, healthcare measures to deal with COVID-19 pandemic, there is also an imminent requirement for theresearch to improvethe global economy, which has taken a tremendous beating and is unlikely to recover in the near future [ 7 , 8 ].

4. Conclusion

COVID-19 pandemic is a public health emergency of international concern.It has posed new challenges to the global research community. With the help of academic research, there is a need for a better understanding of the COVID-19 and its socio-economic ramifications on society. The future research will be multi-disciplinary and trans-national.We see a new wave of research in the biological and the medical sciences for the well-being of the civilization.

Declaration of competing interest

• Open access
• Published: 25 January 2023

Limitations of COVID-19 testing and case data for evidence-informed health policy and practice

• Elizabeth Alvarez   ORCID: orcid.org/0000-0003-2333-0144 1 ,
• Iwona A. Bielska 1 ,
• Stephanie Hopkins 1 ,
• Ahmed A. Belal 1 ,
• Donna M. Goldstein 2 ,
• Jean Slick 3 ,
• Sureka Pavalagantharajah 4 ,
• Anna Wynfield 2 ,
• Shruthi Dakey 5 ,
• Marie-Carmel Gedeon 6 ,
• Edris Alam 7 &
• Katrina Bouzanis 8  

Health Research Policy and Systems volume  21 , Article number:  11 ( 2023 ) Cite this article

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Metrics details

Coronavirus disease 2019 (COVID-19) became a pandemic within a matter of months. Analysing the first year of the pandemic, data and surveillance gaps have subsequently surfaced. Yet, policy decisions and public trust in their country’s strategies in combating COVID-19 rely on case numbers, death numbers and other unfamiliar metrics. There are many limitations on COVID-19 case counts internationally, which make cross-country comparisons of raw data and policy responses difficult.

Purpose and conclusions

This paper presents and describes steps in the testing and reporting process, with examples from a number of countries of barriers encountered in each step, all of which create an undercount of COVID-19 cases. This work raises factors to consider in COVID-19 data and provides recommendations to inform the current situation with COVID-19 as well as issues to be aware of in future pandemics.

Peer Review reports

Since the emergence of coronavirus disease 2019 (COVID-19) in Wuhan, China, the world has faced serious data issues, ranging from a lack of transparency on the emergence, spread and nature of the virus to an absence of grounded comparative analyses, with temporal differences considered, about emerging social and economic challenges [ 1 , 2 ]. Most critically, scientists have lacked data to conduct analyses on non-pharmaceutical interventions (NPIs), including policies and strategies that governments have engaged to mitigate the situation, and how these have varied across regions, presumably affecting both short- and long-term outcomes [ 1 , 2 ].

Out of all the strategies implemented to date, physical distancing policies have emerged as one of the more effective NPIs to battle COVID-19 [ 3 , 4 ]. While physical distancing policies have been the mainstay in the battle against COVID-19, there has been a call to understand which forms of physical distancing policies are effective so that targeted and less disruptive measures can be taken in further waves of this pandemic and future pandemics [ 1 , 2 , 5 , 6 ]. The best time to institute physical distancing policies and what happens when and how they are eased remain unclear. There are many aspects of distancing, such as recommendations for maintaining a physical distance in public, banning group gatherings (the maximum number and where they take place), or complete lockdowns, that complicate their assessment. Timing and synergies of policies and sociodemographic and political factors play a role in the effectiveness of these policies [ 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. Some hypothesized sociodemographic factors for increased exposure and severity of COVID-19 include living in a long-term care facility or being institutionalized, age (older), gender (mixed findings), having comorbidities (including high blood pressure, diabetes, obesity, immunocompromised status, tobacco smoking) and social vulnerabilities including race or ethnicity. Also relevant is the carrying capacity and infrastructure of health systems. These factors pose challenges for comparison among countries. Comparison is a prime requisite for evaluating the effectiveness of implementation of various policies between countries. Policymakers and the public have been using metrics such as number of cases, number of deaths and testing capacity to make policy or programme decisions or to decide whether to trust the actions of their governments, respectively.

An international team of researchers has been collecting data on physical distancing policies and contextual factors, such as health and political systems and demographics, to expedite knowledge translation (which means applying high-quality research evidence to processes of decision making) on the effect of policies and their influence on the epidemiology of COVID-19 [ 14 , 15 , 16 ]. Through this work, we identified gaps in the accuracy of reported numbers of COVID-19 cases and deaths, which make cross-country comparisons of the raw data, indexes using the raw data, and policy outcomes challenging [ 7 , 17 ]. While the work of this team is ongoing, this paper limits the findings from the inception of the pandemic to the end of 2020. It is important to understand the limitations of available COVID-19 data in order to properly inform decision making, especially at the outset as a novel infectious disease. This paper focuses on the testing and reporting cycle (Fig.  1 ) and provides examples from a number of countries of possible barriers leading to inaccurate data on reported COVID-19 cases. It also describes other cross-cutting implications of COVID-19 data for policy, practice and research, including reported deaths, missing information, implementation of policy, and unpredictable population behaviour. Furthermore, it calls into question analyses performed to date, which do not account for a number of known data gaps.

COVID-19 testing and reporting cycle. *The icons in this figure are in the public domain (Creative Commons CC0 1.0 Universal Public Domain) and were obtained from Wikimedia Commons at: https://commons.wikimedia.org/wiki/File:Medical_Library_-_The_Noun_Project.svg ; https://commons.wikimedia.org/wiki/File:Home_(85251)_-_The_Noun_Project.svg ; https://commons.wikimedia.org/wiki/File:Laboratory_-_The_Noun_Project.svg ; https://commons.wikimedia.org/wiki/File:Noun_project_1063.svg ; https://commons.wikimedia.org/wiki/File:Analysis_-_The_Noun_Project.svg

It is important to note that Fig.  1 only represents the testing and reporting cycle, which leads to counting of cases, and it does not include COVID-19 contact tracing and case management; however, we recognize that testing, contact tracing and case management are intricately linked to each other in the spread of COVID-19 [ 18 , 19 ]. As ‘Our World in Data’ states, “Without testing there is no data.” [ 20 ]. Understanding the links between testing, data and action underlies country responses to the pandemic. Ultimately, this work serves to provide a basis to improve pandemic planning, surveillance and reporting systems, and communications.

In Fig.  1 , the first level of testing is at the healthcare recipient level (Sect. “ Healthcare recipient level ”), followed by sample collection and processing (Sect. “ Sample collection and processing ”) and surveillance and reporting (Sect. “ Surveillance and reporting ”). Each level will be further explained below and examples provided as to potential or actual barriers at each level. These descriptions are not exhaustive, and nuanced understanding of the context will be needed to evaluate these steps and potential barriers in different settings.

Healthcare recipient level

Testing starts with individuals getting tested. There may be times when it is predetermined who gets tested and when, such as health workers getting tested prior to starting work in a long-term care facility or travellers returning from overseas [ 21 , 22 ]. However, most individuals are tested in the community, where a number of steps predicate individuals’ decisions to seek out testing. First, case definition, testing criteria and referral for testing influence our understanding of what the disease entity is and whether people are encouraged or discouraged to get tested. Given the novel status of COVID-19, there were challenges at the onset of this pandemic in establishing a working case definition. In China, arguably the leader in COVID-19 knowledge at the time, the case definition for reporting changed over time and between places [ 23 ]. These definitions were not always consistent with one another. Between 22 January and 12 February 2020, China’s National Health Commission had revised the COVID-19 outbreak response guidelines at least six times, resulting in significant differences in the daily counts due to changes over time in the definition of a case [ 24 ]. Adding to the uncertainty, the World Health Organization did not publish case definition guidelines until 16 April 2020, long after many countries had created their own working case definitions [ 25 ]. Although changes in methodology are expected as we learn more about the disease and as new variants emerge, these changes have implications for case counts [ 23 , 25 ]. Yet, communication does need to be flexible during a crisis. For example, little was known about asymptomatic COVID-19 spread at the beginning of the pandemic. As more evidence was garnered on this topic, information about precautions and testing criteria needed to be flexible to keep up with what was known [ 26 ].

Not only have case definitions changed over time, criteria for testing have changed over time and across jurisdictions on the basis of a number of factors, such as better understanding of the disease process, availability and capacity for testing, and national and local strategies for addressing the pandemic [ 27 ]. In some places, testing criteria were narrow, which discouraged people from getting tested because they did not fit the criteria. In its early response, Canada only tested symptomatic people returning from specific countries known to have high numbers of cases of COVID-19 [ 18 ]. Given that there were no treatments and media reported that the hospitals were overwhelmed, people were also discouraged from seeking medical attention unless they warranted hospitalization. If people were feeling unwell, but not needing to be on a ventilator, testing might not have been deemed necessary. Shifting testing criteria and differences in referral channels for testing, such as going through public health or needing a physician referral versus self-referrals, could create additional barriers.

Depending on the testing strategy, whether based on specific criteria or population-based, will make a difference for number of COVID-19 cases identified. Changes in criteria for testing sometimes led to increased demand without a corresponding increase in the availability of testing resources, which then led to delays in accessing tests [ 28 ]. Additionally, as different sectors, such as schools, resumed in-person activity, there was an increased demand for testing within certain population groups. Again, testing capacity could not always keep up with demand, leading, in some instances, to further limitations of who could be tested to prioritize resources for testing [ 27 ].

In the case that an individual has a choice to get tested, once a person is determined to be eligible for testing, that person has to decide whether or not to get tested, following a decisional process for getting tested, which can be affected by factors such as the availability of education and decision supports, health literacy, health status, trade-offs between knowing their results and potential economic and social consequences, health system complexity, and personal costs, such as time and out-of-pocket expenses [ 29 , 30 ]. Availability of education and decision support is needed for people to understand that there is a pandemic, what that means, how it might impact them, how and where to get tested (if available) and why getting tested is important for them or their loved ones. This relies on accurate and timely information, which is discussed in more detail in Sect. “ Governance and knowledge translation ”.

Furthermore, health literacy can involve a general understanding of factors that affect health or it can be specific to a disease entity, such as the virus that causes COVID-19. Health status can decrease the number of people seeking testing if they have mild symptoms and decide it is not worthwhile to seek testing or care, or they may not fit the testing criteria. On the other hand, some people with severe symptoms may not have the physical resources to go to a testing centre.

Of course, even individual-level factors are affected by broader systematic determinants of health. As the gravity of the pandemic took hold, jurisdictions began implementing more robust isolation policies to prevent the spread of COVID-19. These policies included self-isolation or a quarantine period for those who tested positive or who had come in contact with a known case. In many countries, governments provided economic relief to support people who were unable to work [ 31 , 32 ]. However, in countries such as Brazil and Mexico there were limited social safety nets, and in many other countries such as the USA, COVID-19 exposed gaps in these nets [ 33 , 34 ]. This created an economic barrier for people to access testing, as a positive test would force them to stay home without adequate financial means to survive. On 28 April 2020, the French Prime Minister, Edouard Philippe, urged the population of France to “protect-test-isolate”; meanwhile, containment measures generated a “disaffiliation process” among migrants and asylum seekers. Absence of work, isolation from French society, and fear of being checked by the police brought individuals into a “disaffiliation zone” marked by social non-existence, in a context of global health crisis [ 35 ].

Health systems themselves created a barrier to testing through their slow response to testing requests, causing some individuals to abandon testing [ 36 ]. In some countries, testing was expensive and not offered in the poorest communities [ 37 ]. For those travelling, mandatory testing, with varying requirements between different countries and potential out-of-pocket costs, increased the complexity of getting tested. Furthermore, competing crises may have lowered the number of people seeking testing due to other, more immediate, priorities, such as floods or wildfires [ 38 , 39 , 40 , 41 ].

Sample collection and processing

Once a person decides to seek testing, tests must be available and accessible and there must also be sufficient test processing centres. While these factors are often lumped together, it is important to distinguish these two steps in the testing cycle as they often require different structural and/or operational components.

Tests and testing sites

For an individual to get tested, there must be availability of testing sites and accessibility to these testing sites. Testing sites may include already available clinic, hospital or community sites, or assessment centres which are created for the purpose of testing. Having separate assessment centres can ease conflicting burdens on already overwhelmed health systems, and they can allow for efficiency in the process of testing and in keeping potentially infectious individuals separate from those who are seen for other ailments. Not only do testing sites have to be available, they have to be accessible. Times of operation, parking and other accessibility considerations are important. Testing sites can be centralized in one or several locations, where people have to find transportation to the sites, or can be mobile sites, which can increase access to those in rural/remote areas or those with mobility or transportation issues. Drive-thru testing has been showcased in countries such as South Korea [ 42 ]. However, limitations also exist with drive-thru sites for those who do not own a vehicle, or those who have to drive long distances or endure long wait times [ 43 ]. In areas with poor health system infrastructure, lack of access can exacerbate inequities in testing.

Operational components include the need for adequate human resources and testing supplies. In Ontario, Canada, assessment centres were slow to set up and there was a lack of swabs and other testing supplies [ 18 ]. In France, laboratories struggled to keep up with testing demands due to delays in receiving chemicals and testing kits produced abroad, given France’s reliance on global supply chains [ 44 ]. Bangladesh had a very limited number of case testing capacity in the beginning of the outbreak. The country conducted fewer than 3000 tests in the first four weeks of the outbreak between 8 March and 5 April 2020 for its 164 million population as well as 155,898 overseas passengers, some arriving from hard-hit countries such as Italy, allowing for community transmission [ 45 ].

The method of specimen collection and specimen management for processing are also important considerations. Specimen collection has varied between contexts and over time [ 46 ]. Nasopharyngeal, nasal and throat swabs have been used in community settings. Saliva tests and blood samples, mainly for hospitalized patients, are other methods of obtaining specimens. Each of these testing modalities has different properties, but none is 100% sensitive or able to pick up all positive cases of COVID-19. There are reports of very ill patients testing negative on multiple occasions on nasopharyngeal samples but subsequently testing positive from lung samples [ 47 , 48 ]. Specimen management requires the proper labelling, storage and transportation of samples from the testing site to the laboratory for processing.

Laboratories

Laboratory preparedness and laboratory capacity played crucial roles in COVID-19 testing globally [ 27 , 49 ]. Issues with this preparedness and capacity, along with lack of testing supplies, resulted in “lack of testing” as a prime factor for not having accurate numbers of COVID-19 cases, especially at the beginning of the pandemic. Laboratory capacity includes human resources and specimen processing supplies, often called the testing kits, which require specific reagents and equipment. Over time, countries with low laboratory preparedness focused on improving their testing capacities [ 49 ]. Since the start of the pandemic, Germany was touted as testing widely and therefore having a robust ability to contact trace in order to find people who may transmit the virus causing COVID-19. However, other countries struggled to get testing in place. In the USA, initial tests developed were invalid, which delayed the ability to distribute and complete tests [ 50 ]. This was further exacerbated by bureaucratic/institutional red tape which centralized testing to the Centers for Disease Control and Prevention (CDC) and prohibited local public health and commercial laboratories from developing or administering more effective tests [ 51 ]. Supply chain management issues for swabs, transport media and reagents slowed down early testing in multiple countries [ 27 ].

Once testing methods have been established, there are a number of tests available for COVID-19 [ 52 ]. Test properties include the sensitivity and specificity of a test, among others, and these can vary by test. Therefore, the type of test used can also influence case counts. Recent studies have highlighted the need to validate laboratory tests and share the results during a pandemic. Evidence from a study in Alberta, Canada suggested that variations in test sensitivity for the virus causing COVID-19, particularly earlier in a pandemic, can result in “an undercounting of cases by nearly a factor of two” (p. 398) [ 53 ]. With rapid tests and home-approved testing kits available during the course of the pandemic, testing properties can vary even more greatly [ 52 , 54 , 55 ].

Surveillance and reporting

Once individuals have been tested and the results are processed, surveillance and reporting systems must be in place to communicate that information back to individuals, public health officials or others involved in case management or treatment, and to politicians and other stakeholders to act on this information and prevent further spread.

Data systems

Data management refers to the inputting and tracking of data. However, because of the need to quickly and accurately inform the public and decision makers in the time of a crisis, coordination of information technology is needed to align all the various data management systems within a jurisdiction and internationally. For example, each hospital system, clinic or laboratory may have separate electronic medical record or data management systems. Not many countries maintain a common database system for COVID-19-related management (testing, response, etc.). Even if database management systems are in place, lack of trained professionals, serious lags in updating data, challenges with interdepartmental coordination among various task force members, and new innovations such as artificial intelligence, health tracking apps, telemedicine and big data, which are suddenly in place, can lead to disrupted transparency. An exception is China, which developed a highly responsive national notifiable disease reporting system (NNDRS) in the aftermath of severe acute respiratory syndrome (SARS) [ 56 , 57 ]. The United Nations Department of Economic and Social Affairs statistics division launched a common website for improving the data capacities of countries [ 58 ]. This information has to be further coordinated to create larger and more robust surveillance and notification systems. Robust surveillance systems help decision makers know what is happening locally or how a disease is moving through populations. Notification systems are needed for sharing information between the testing site, laboratory and public health or local health agencies for case management and contact tracing and for letting people know their test results in a timely manner to help prevent further spread. The COVID Tracking Project has highlighted many discrepancies in USA reporting and surveillance, demonstrating unreliability of the data [ 59 ]. For example, hospitals were required to change how COVID-19 data were relayed to the federal government, and the switch from reporting through the CDC to the Health and Human Services (HHS) system resulted in misreporting of data and administrative lags across several states. Countries’ national-level CDCs collect information from state and local sources. The time lag can hence be one of the reasons for misleading the overall comprehensive pandemic impact. Lastly, with rapid, point-of-care and home tests available, keeping track of positive cases may be even more difficult, and COVID-19 case counts could be even further artificially decreased [ 60 ]. These tests could make contact tracing even more difficult if there is a lack of disclosure from the user end. It is important to note that, while there are many available sites for international COVID-19 data comparisons, including John’s Hopkins COVID-19 Dashboard [ 61 ], Worldometer [ 62 ], Our World in Data [ 20 ] and the World Health Organization (WHO) COVID-19 Dashboard [ 63 ], these all rely on locally-acquired data for their reporting, and therefore fall into and potentially augment the same fallacies discussed in this paper.

Governance and knowledge translation

Even with robust surveillance and notification systems, transparency and accountability are important for informing decision makers and the public. Decision makers need to know what the health and laboratory systems are finding so that evidence-informed policy and practice decisions can be made for the public good. At the same time, trust in government and government responses rely in part on perceived transparency of government by the public [ 64 , 65 ]. Accountability spans all through the spectrum discussed in the testing and reporting cycle, in a whole-of-society approach. Individuals are accountable for knowing when to get tested, getting tested and following public health guidelines and other policies. The public health and healthcare systems are accountable for planning testing and sharing information. Decision makers are accountable for transparency in sharing information, communicating appropriately with the public and relevant stakeholders, and making decisions for those they represent. In parts of Russia, there were two separate reports for those who died from COVID-19 and those who were positive but died from other causes [ 25 ]. In Florida, state officials instructed medical examiners to remove causes of death in their lists [ 66 ]. In China, despite having a highly responsive national data surveillance and reporting system, at the beginning of the pandemic, cases were only reported to the system once they had been approved by local members of government who only allowed cases with a direct connection to the original source of the outbreak, the seafood market, to be recorded [ 67 ].

Political will has been shown to be a barrier or facilitator in the fight against COVID-19. Examples of good leadership and political will can be found in places like New Zealand, where decisions were made early on, implemented, supported and continued to be informed by emerging evidence, or as described, following “science and empathy”[ 68 ]. Poor leadership has also come through clearly during this pandemic. Tanzania, Iran, the USA, Brazil and Egypt are only a handful of countries demonstrating the impact of political will on the course of the pandemic, in some cases resulting from subversion and corruption. Communication in these countries was often not transparent or mixed, and accountability for the lack of decision making or poor decision making was limited or non-existent in the pandemic’s outset. Tanzania stopped reporting cases due to political optics [ 30 , 69 ]. Iran’s Health Ministry reported 14,405 deaths due to COVID-19 through July 2020, which was a significant discrepancy from the 42,000 deaths recorded through government records [ 70 ]. The number of cases was also almost double those reported, 451,024 as compared with 278,827. One main reason for releasing underestimated information about the cases was considered to be upcoming parliamentary elections [ 70 , 71 ]. The former president of the USA, Donald Trump, often flouted public health and healthcare expert advice [ 72 ]. The Washington Post reported that Brazil was testing 12 times fewer people than Iran and 32 times fewer people than the USA, and hospitalized patients and some healthcare professionals were not tested in an effort to lower the case numbers [ 73 ]. Hiding numbers of deaths from COVID-19, whether intentionally or inadvertently, shored up far-right supporters of Brazil’s President Bolsonaro at a time when he was facing possible charges of impeachment for corruption and helped bolster the President’s messaging that the pandemic was under control. This further enabled a large swath of the population to call for less strict rules around COVID-19 and a quick reopening of the economy. Similarly, in July 2020, it was reported that at least eight doctors and six journalists had been arrested because they criticized the Egyptian government’s response to the pandemic [ 74 ].

Lastly, communication and information dissemination link to every piece of this process. Why, when and how people seek testing, how and where to set up testing sites, supply chain management, setting up and managing data systems, and policy decision making all work in a cycle. Good communication between systems and dissemination of information to the public and relevant stakeholders is imperative during a crisis, such as the COVID-19 pandemic. The amount of information available and rapid change in information creates an infodemic problem. ‘Infodemic’ is a term used by the WHO in the context of COVID-19 and refers to informational problems, such as misinformation and fake news, that accompany the pandemic [ 75 ]. Addressing the infodemic issue was highlighted as one of the prominent factors needed to improve future global mitigation efforts [ 76 ]. A report published in the second week of April 2020 by the Reuters Institute for the Study of Journalism at the University of Oxford found that roughly one-third of social media users across the USA, as well as Argentina, Germany, South Korea, Spain and the UK, reported seeing false or misleading information about COVID-19 [ 77 ]. The presidents of Brazil and the USA were themselves sources of misinformation, as they were seen in public without masks and touting the benefits of hydroxychloroquine after it was largely known that harms outweighed benefits of its use [ 72 , 78 , 79 ]. Having clear public health communications, from trusted sources, and breaking down silos between systems could be helpful in combating ever-changing information during a pandemic.

Other implications of COVID-19 data for policy, practice and research

There are several cross-cutting issues separate, but related, to the testing and reporting cycle which arose during this work. These issues also affect COVID-19 case counts and optimal timing of policies: how deaths are reported, missing information, implementation of policies, and unpredictable population behaviour.

Reported deaths

Deaths from COVID-19 tend to occur weeks after infection; therefore, assessments of policy changes using death counts need to account for this timing. However, reported death counts from COVID-19 carry many similar limitations given lack of testing for those who are deceased, attributing cause of death to COVID-19-related complications, processes for declaring deaths and causes of deaths, and lack of transparency [ 80 ]. In Brazil, hospitalized patients were not being tested, and deaths were attributed to respiratory ailments [ 73 ]. Further, COVID-19 deaths from the City of Rio de Janeiro’s dashboard were blacked out for 4 days in May (22–26 May 2020) [ 81 ]. When the dashboard was restarted, the death count was artificially lowered by changing the cause of death from COVID-19 to its comorbidities. Additional changes included requiring a confirmed COVID-19 test at the time of death in order for the death certificate to list COVID-19 as the cause; however, the results of the test often came after the death certificates were issued [ 81 ]. In Italy, the reverse occurred where only those in hospital were counted as COVID-19 deaths, while many people died at home or in care homes without being tested [ 82 , 83 ]. In Ireland, early discrepancies in reported deaths were noted between official government figures and an increase in deaths noted on the website Rip.ie, which has served as a public forum disclosing deaths and wake information in line with Irish funeral traditions. Information from this forum was used to re-assess mortality and in some cases aid epidemiological modelling [ 84 ].

Missing information

Given the lack of access to treatments at the beginning of the pandemic, understanding who was at highest risk of obtaining or dying from COVID-19 was important to know in order to develop appropriate policies that balanced health with social and economic impacts of the pandemic. Early data showed a sex and age gradient for COVID-19 cases and deaths. However, not all countries report data by sex and/or age. Race/ethnicity and sociodemographic findings were not collected or reported early in the pandemic [ 85 ]. France has been criticized for laws which prohibit the collection of race and ethnicity data, since they lack data which demonstrate whether certain groups are overrepresented in COVID-19 cases and deaths [ 86 , 87 ]. Another aspect of missing data early in the pandemic was that of asymptomatic spread. Due to limited testing early in the pandemic, asymptomatic cases were not picked up. Population-based studies are being conducted to better understand the role of asymptomatic and pre-symptomatic spread of COVID-19 in different population groups, such as children [ 26 ].

Implementation of policy

Population-level strategies since the start of the pandemic and reported findings in the literature go hand and hand. Cause and effect are difficult to attribute. For example, early literature looking at the role of children on the spread of COVID-19 found that children played a small role. This was to be expected given that many schools around the world closed, and children would not be exposed through transportation and workplaces as adults would be. Therefore, family spread would naturally flow from adults to children given these circumstances. In addition, many places were not testing mild to asymptomatic cases, which were more commonly found in children. Publications early on related to the few severe COVID-19 cases in children or to school-related cases in places that had low community transmission rates of COVID-19 and were following public health guidelines [ 88 ]. Limitations of these data have been described, yet findings have been used to justify specific policies in places that were dissimilar, with expected results ensuing, such as an increase in community transmission and school closures due to COVID-19 infections [ 89 ]. Therefore, it is even more important to understand the context of policies before applying them to various jurisdictions.

Unpredictable population behaviour

There is a difference between stated policy, implementation and enforcement. To understand which policies worked to combat COVID-19, it is important to consider the level of compliance with stated policies. Some people may follow recommended approaches for protective actions while others may not comply and see these recommendations as problematic [ 90 ]. For example, people may change their behaviours in anticipation of an announced change; for example, individuals may start working from home even before it is enforced or if it is never officially mandated, or people may go on a shopping spree prior to known closures [ 91 , 92 ]. Of course, people’s behaviours may also be dependent on a disconnect between policy messages at different levels of government and exacerbated by rapid updates in a fast-moving pandemic of unknown properties and the associated information overload. Therefore, communication management and clarity are of utmost importance during a crisis.

Discussion and recommendations

The need for cross-country comparison is necessary for understanding the effectiveness of policies in various countries. Policy decisions are being made and judged on the basis of case numbers, deaths and testing, among others. Understanding the steps and barriers in testing and reporting data related to COVID-19 case numbers can help address the limitations of data to strengthen these systems for future pandemics and can also help in the interpretation of findings across jurisdictions. Robust and timely public health measures are needed to decrease the health, social and economic ramifications of the pandemic. Even with available vaccines, it will still take time to have sufficient population coverage internationally.

There are a few assumptions considered in this paper. First, we assume that the reported numbers for each country are not inflated. There could be some cases that are counted more than once if repeated tests are taken and the person continues to test positive. Most data do not disclose how often this occurs, but it is likely not a significant issue for population reports, at least at from the beginning of the pandemic [ 20 ]. Next, ideally COVID-19 case counts are accurate. This is the assumption that is made by policymakers and the public in judging their decisions and their outcomes. We argue that the reported COVID-19 data are likely an undercount of actual cases. The reasons are highlighted in this paper.

Future global discussions will continue around who is most affected by COVID-19 and how to best prepare for pandemics, among others. COVID-19 case and death counts will be used in determining successful approaches. It is important to understand the context of COVID-19 data in these discussions, especially with respect to other global indicators that may look to COVID-19 data, such as the Sustainable Development Goals (SDGs) through improvement of early warning, risk reduction and management of national and global health risks [ 93 ]. Specifically, SDG 3 (good health and wellbeing) with an emphasis on highlighting the lacunas in informed data tying policy and epidemiology, SDG 10 to reduce inequalities within and among countries, and SDG 16 (peace, justice and strong institutions) with a goal to build effective and accountable institutions at all levels. This research also contributes to the Sendai Framework for Disaster Risk Reduction, specifically priority 2, strengthening disaster risk governance to manage disaster risk, and priority 3, investing in disaster risk reduction for resilience [ 94 ]. Unfortunately, there is little published on good governance in reporting systems during COVID-19, and our findings in this area are limited to media and news sources. Future research could focus on this critical aspect.

Decision makers could consider the following overarching recommendations, contextualized to their individual jurisdictions (i.e. regional, country, province, territory, state), to evaluate the testing and reporting cycle and improve accuracy and comparability of COVID-19 data:

Understand barriers to accurate testing and reporting —This paper lays out the steps in the testing and reporting process and components of these steps. Barriers are described at each of these steps, and examples are provided.

Address barriers to testing and reporting —Understanding barriers in the testing and reporting process can uncover facilitators. Each setting will deal with different barriers. Ultimately, political will, capacity building and robust information systems will be needed to address any of these barriers.

Transparency and accountability for surveillance and reporting —Any attempt to assign causality to these policies must take into account the timing and quality of surveillance data. Data quality issues, such as completeness, accuracy, timeliness, reliability, relevance and consistency, are important for surveillance and reporting [ 95 , 96 ].

Invest in health system strengthening, including surveillance and all-hazards emergency response plans —COVID-19, as this and past pandemics have shown, is not just a health issue, and instead requires community, health systems, social systems and policy approaches to mitigate its effects. Preparing for infectious disease outbreaks and other crises needs to incorporate all-hazards emergency response plans in order to have all the necessary resources in place at the time of the events.

Identify promising communication strategies —Research is needed to understand how messages conveyed at all stages of a pandemic are received and understood at the micro-level and used by the public [ 97 ]. Development of communication strategies aimed at promoting good understanding of information may defer inappropriate behaviours.

Invest in research to further understand data reporting systems and policy strategies and implementation . Research could compare global COVID-19 data reporting platforms mentioned in this article to see from where they obtained their raw data to further understand data reporting accuracy and comparability of data over time and whether any limitations of data were noted. Further research could address what policy and implementation strategies worked in a variety of settings to strengthen future recommendations for emerging pandemics.

The use and effectiveness of government responses, specifically pertaining to physical distancing policies in the COVID-19 pandemic, has been evolving constantly. Testing is a measure of response performance and becomes a focal point during an infectious disease pandemic as all countries are faced with a similar situation. COVID-19 represents a unique opportunity to evaluate and measure success by countries to control its spread and address social and economic impacts of interventions. Understanding limitations of COVID-19 case counts by addressing factors related to testing and reporting will strengthen country responses to this and future pandemics and increase the reliability of knowledge gained by cross-country comparisons. Alarmingly, with COVID-19 having asymptomatic spread, lack of testing can discredit the efforts of an entire community, not to say an entire population.

Availability of data and materials

All data generated or analysed during this study are included in this published article.

Abbreviations

Centers for Disease Control and Prevention

Coronavirus disease 2019

Health and Human Services

National notifiable disease reporting system

Non-pharmaceutical interventions

Severe acute respiratory syndrome

Sustainable Development Goals

World Health Organization

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Acknowledgements

The authors acknowledge Dr. Neil Abernethy’s contributions to the COVID-19 Policies and Epidemiology Working Group.

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School of Medicine, McMaster University, Hamilton, ON, Canada

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Alvarez, E., Bielska, I.A., Hopkins, S. et al. Limitations of COVID-19 testing and case data for evidence-informed health policy and practice. Health Res Policy Sys 21 , 11 (2023). https://doi.org/10.1186/s12961-023-00963-1

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COVID-19 Limitations Unique Opportunity for Researchers to Decrease Digital Divide

Researchers need to develop new ways to reach rural participants.

• by Karen Nikos-Rose
• April 29, 2020

The COVID-19 shelter-in-place orders and other limitations could offer researchers the chance to use technology to decrease the digital divide and disparities in academic research, suggests a University of California, Davis, professor in a new commentary.

“While I know many of my colleagues are frustrated with this pause in clinical research, it is actually a unique opportunity,” said Leigh Ann Simmons, chair of the Department of Human Ecology, whose research interests include increased equity in health care delivery and chronic disease prevention in rural areas. “People who live in rural areas are often left out of clinical trials that can benefit them, partly because they are not near large medical centers,” she said. This includes migrant workers, farmers and the general public who live in outlying areas.

She is co-author of the commentary , “Navigating Nonessential Research Trials During COVID 19: The Push We Needed for Using Digital Technology to Increase Access for Rural Participants?” published in The Journal of Rural Health earlier this month. Co-author is Devon Noonan, a researcher at Duke University.

Simmons said some research in which research subjects have to be contacted personally for interviews, testing or surveys has stopped since social distancing went into effect. This is a mistake, she said. “If we think creatively we can extend our reach.”

“We need to stop and think,” said Simmons, who is herself currently engaged in two rural health prevention studies that are being conducted solely using remote strategies. “How can we do our work remotely? Is there a way to get our data without human contact? And if we go this route, how can we include people who may not usually participate in our studies?”

It is well known, the authors said in their paper, that rural populations experience significant health disparities, especially in rates of common chronic diseases such as heart disease, diabetes, cancer and the associated health behaviors such as diet, physical activity, and tobacco and other substance use. “These disparities are in part due to rural residents’ lack of access to, knowledge about, and participation in clinical trials,” they said.

Participation in such trials is made more difficult in these areas too by lack of good internet access. Simmons said this could be augmented by researchers using community centers or regional facilities, or other community partners, to enable access for those in the study. Regional facilities could also be used to help with data and sample collections.

Further, state departments of heath “could replicate the partnership that the California Department of Education initiated with Google to distribute mobile hotspots to areas without broadband access so that K-12 education could continue amid school closures associated with shelter-in-place orders,” the authors suggest.

“Moving to remote clinical trials is not without its challenges, especially for studies that are well underway,” she emphasizes. “Importantly, the steps we take now to continue nonessential research remotely may provide the evidence we need to ensure that future studies target these hard-to-reach populations for study inclusion.”

Establishing remote access to clinical trials will serve to not only decrease rural clinical trial disparities, the authors said, but also to promote rural health equity into the next decade and beyond.

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Karen Nikos-Rose, News and Media Relations, 530-219-5472, [email protected]

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Research Article

The challenges arising from the COVID-19 pandemic and the way people deal with them. A qualitative longitudinal study

Contributed equally to this work with: Dominika Maison, Diana Jaworska, Dominika Adamczyk, Daria Affeltowicz

Roles Conceptualization, Funding acquisition, Methodology, Project administration, Supervision, Writing – original draft, Writing – review & editing

Affiliation Faculty of Psychology, University of Warsaw, Warsaw, Poland

Roles Formal analysis, Investigation, Writing – original draft, Writing – review & editing

Roles Conceptualization, Formal analysis, Investigation, Methodology, Writing – original draft, Writing – review & editing

* E-mail: [email protected]

Roles Conceptualization, Formal analysis, Investigation, Methodology

• Dominika Maison, 
• Diana Jaworska, 
• Dominika Adamczyk, 
• Daria Affeltowicz

• Published: October 11, 2021
• https://doi.org/10.1371/journal.pone.0258133
• Peer Review
• Reader Comments

The conducted qualitative research was aimed at capturing the biggest challenges related to the beginning of the COVID-19 pandemic. The interviews were carried out in March-June (five stages of the research) and in October (the 6 th stage of the research). A total of 115 in-depth individual interviews were conducted online with 20 respondents, in 6 stages. The results of the analysis showed that for all respondents the greatest challenges and the source of the greatest suffering were: a) limitation of direct contact with people; b) restrictions on movement and travel; c) necessary changes in active lifestyle; d) boredom and monotony; and e) uncertainty about the future.

Citation: Maison D, Jaworska D, Adamczyk D, Affeltowicz D (2021) The challenges arising from the COVID-19 pandemic and the way people deal with them. A qualitative longitudinal study. PLoS ONE 16(10): e0258133. https://doi.org/10.1371/journal.pone.0258133

Editor: Shah Md Atiqul Haq, Shahjalal University of Science and Technology, BANGLADESH

Received: April 6, 2021; Accepted: September 18, 2021; Published: October 11, 2021

Copyright: © 2021 Maison et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files ( S1 Dataset ).

Funding: This work was supported by the Faculty of Psychology, University of Warsaw, Poland from the funds awarded by the Ministry of Science and Higher Education in the form of a subsidy for the maintenance and development of research potential in 2020 (501-D125-01-1250000). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Introduction

The coronavirus disease (COVID-19), discovered in December 2019 in China, has reached the level of a pandemic and, till June 2021, it has affected more than 171 million people worldwide and caused more than 3.5 million deaths all over the world [ 1 ]. The COVID-19 pandemic as a major health crisis has caught the attention of many researchers, which has led to the creation of a broad quantitative picture of human behavior during the coronavirus outbreak [ 2 – 4 ]. What has been established so far is, among others, the psychological symptoms that can occur as a result of lockdown [ 2 ], and the most common coping strategies [ 5 ]. However, what we still miss is an in-depth understanding of the changes in the ways of coping with challenges over different stages of the pandemic. In the following study, we used a longitudinal qualitative method to investigate the challenges during the different waves of the coronavirus pandemic as well as the coping mechanisms accompanying them.

In Poland, the first patient was diagnosed with COVID-19 on the 4 th March 2020. Since then, the number of confirmed cases has grown to more than 2.8 million and the number of deaths to more than 73,000 (June 2021) [ 1 ]. From mid-March 2020, the Polish government, similarly to many other countries, began to introduce a number of restrictions to limit the spread of the virus. These restrictions had been changing from week to week, causing diverse reactions in people [ 6 ]. It needs to be noted that the reactions to such a dynamic situation cannot be covered by a single study. Therefore, in our study we used qualitative longitudinal research in order to monitor changes in people’s emotions, attitudes, and behavior. So far, few longitudinal studies have been carried out that investigated the various issues related to the COVID-19 pandemic; however, all of them were quantitative [ 7 – 10 ]. The qualitative approach (and especially the use of enabling and projective techniques) allows for an in-depth exploration of respondents’ reactions that goes beyond respondents’ declarations and captures what they are less aware of or even unconscious of. This study consisted of six stages of interviews that were conducted at key moments for the development of the pandemic situation in Poland. The first stage of the study was carried out at the moment of the most severe lockdown and the biggest restrictions (March 2020) and was focused on exploration how did people react to the new uncertain situation. The second stage of the study was conducted at the time when restrictions were extended and the obligation to cover the mouth and nose everywhere outside the household were introduced (middle of April 2020) and was focused at the way how did people deal with the lack of family gatherings over Easter. The third stage of the study was conducted at the moment of announcing the four stages of lifting the restrictions (April 2020) and was focused on people’s reaction to an emerging vision of getting back to normalcy. The fourth stage of the study was carried out, after the introduction of the second stage of lifting the restrictions: shopping malls, hotels, and cultural institutions were gradually being opened (May 2020). The fifth stage of the study was conducted after all four stages of restriction lifting were in place (June 2020). Only the obligation to cover the mouth and nose in public spaces, an order to maintain social distance, as well as the functioning of public places under a sanitary regime were still in effect. During those 5 stages coping strategies with the changes in restrictions were explored. The sixth and last stage of the study was a return to the respondents after a longer break, at the turn of October and November 2020, when the number of coronavirus cases in Poland began to increase rapidly and the media declared “the second wave of the pandemic”. It was the moment when the restrictions were gradually being reintroduced. A full description of the changes occurring in Poland at the time of the study can be found in S1 Table .

The following study is the first qualitative longitudinal study investigating how people cope with the challenges arising from the COVID-19 pandemic at its different stages. The study, although conducted in Poland, shows the universal psychological relations between the challenges posed by the pandemic (and, even more, the restrictions resulting from the pandemic, which were very similar across different countries, not only European) and the ways of dealing with them.

Literature review

The COVID-19 pandemic has led to a global health crisis with severe economic [ 11 ], social [ 3 ], and psychological consequences [ 4 ]. Despite the fact that there were multiple crises in recent years, such as natural disasters, economic crises, and even epidemics, the coronavirus pandemic is the first in 100 years to severely affect the entire world. The economic effects of the COVID-19 pandemic concern an impending global recession caused by the lockdown of non-essential industries and the disruption of production and supply chains [ 11 ]. Social consequences may be visible in many areas, such as the rise in family violence [ 3 ], the ineffectiveness of remote education, and increased food insecurity among impoverished families due to school closures [ 12 ]. According to some experts, the psychological consequences of COVID-19 are the ones that may persist for the longest and lead to a global mental health crisis [ 13 ]. The coronavirus outbreak is generating increased depressive symptoms, stress, anxiety, insomnia, denial, fear, and anger all over the world [ 2 , 14 ]. The economic, social, and psychological problems that people are currently facing are the consequences of novel challenges that have been posed by the pandemic.

The coronavirus outbreak is a novel, uncharted situation that has shaken the world and completely changed the everyday lives of many individuals. Due to the social distancing policy, many people have switched to remote work—in Poland, almost 75% of white-collar workers were fully or partially working from home from mid-March until the end of May 2020 [ 15 ]. School closures and remote learning imposed a new obligation on parents of supervising education, especially with younger children [ 16 ]. What is more, the government order of self-isolation forced people to spend almost all their time at home and limit or completely abandon human encounters. In addition, the deteriorating economic situation was the cause of financial hardship for many people. All these difficulties and challenges arose in the aura of a new, contagious disease with unexplored, long-lasting health effects and not fully known infectivity and lethality [ 17 ]. Dealing with the situation was not facilitated by the phenomenon of global misinformation, called by some experts as the “infodemic”, which may be defined as an overabundance of information that makes it difficult for people to find trustworthy sources and reliable guidance [ 18 ]. Studies have shown that people have multiple ways of reacting to a crisis: from radical and even violent practices, towards individual solutions and depression [ 19 ]. Not only the challenges arising from the COVID-19 pandemic but also the ways of reacting to it and coping with it are issues of paramount importance that are worth investigating.

The reactions to unusual crisis situations may be dependent on dispositional factors, such as trait anxiety or perceived control [ 20 , 21 ]. A study on reactions to Hurricane Hugo has shown that people with higher trait anxiety are more likely to develop posttraumatic symptoms following a natural disaster [ 20 ]. Moreover, lack of perceived control was shown to be positively related to the level of distress during an earthquake in Turkey [ 21 ]. According to some researchers, the COVID-19 crisis and natural disasters have much in common, as the emotions and behavior they cause are based on the same primal human emotion—fear [ 22 ]. Both pandemics and natural disasters disrupt people’s everyday lives and may have severe economic, social and psychological consequences [ 23 ]. However, despite many similarities to natural disasters, COVID-19 is a unique situation—only in 2020, the current pandemic has taken more lives than the world’s combined natural disasters in any of the past twenty years [ 24 ]. It needs to be noted that natural disasters may pose different challenges than health crises and for this reason, they may provoke disparate reactions [ 25 ]. Research on the reactions to former epidemics has shown that avoidance and safety behaviors, such as avoiding going out, visiting crowded places, and visiting hospitals, are widespread at such times [ 26 ]. When it comes to the ways of dealing with the current COVID-19 pandemic, a substantial part of the quantitative research on this issue focuses on coping mechanisms. Studies have shown that the most prevalent coping strategies are highly problem-focused [ 5 ]. Most people tend to listen to expert advice and behave calmly and appropriately in the face of the coronavirus outbreak [ 5 ]. Problem-focused coping is particularly characteristic of healthcare professionals. A study on Chinese nurses has shown that the closer the problem is to the person and the more fear it evokes, the more problem-focused coping strategy is used to deal with it [ 27 ]. On the other hand, a negative coping style that entails risky or aggressive behaviors, such as drug or alcohol use, is also used to deal with the challenges arising from the COVID-19 pandemic [ 28 ]. The factors that are correlated with negative coping include coronavirus anxiety, impairment, and suicidal ideation [ 28 ]. It is worth emphasizing that social support is a very important component of dealing with crises [ 29 ].

Scientists have attempted to systematize the reactions to difficult and unusual situations. One such concept is the “3 Cs” model created by Reich [ 30 ]. It accounts for the general rules of resilience in situations of stress caused by crises, such as natural disasters. The 3 Cs stand for: control (a belief that personal resources can be accessed to achieve valued goals), coherence (the human desire to make meaning of the world), and connectedness (the need for human contact and support) [ 30 ]. Polizzi and colleagues [ 22 ] reviewed this model from the perspective of the current COVID-19 pandemic. The authors claim that natural disasters and COVID-19 pandemic have much in common and therefore, the principles of resilience in natural disaster situations can also be used in the situation of the current pandemic [ 22 ]. They propose a set of coping behaviors that could be useful in times of the coronavirus outbreak, which include control (e.g., planning activities for each day, getting adequate sleep, limiting exposure to the news, and helping others), coherence (e.g., mindfulness and developing a coherent narrative on the event), and connectedness (e.g., establishing new relationships and caring for existing social bonds) [ 22 ].

Current study

The issue of the challenges arising from the current COVID-19 pandemic and the ways of coping with them is complex and many feelings accompanying these experiences may be unconscious and difficult to verbalize. Therefore, in order to explore and understand it deeply, qualitative methodology was applied. Although there were few qualitative studies on the reaction to the pandemic [e.g., 31 – 33 ], they did not capture the perception of the challenges and their changes that arise as the pandemic develops. Since the situation with the COVID-19 pandemic is very dynamic, the reactions to the various restrictions, orders or bans are evolving. Therefore, it was decided to conduct a qualitative longitudinal study with multiple interviews with the same respondents [ 34 ].

The study investigates the challenges arising from the current pandemic and the way people deal with them. The main aim of the project was to capture people’s reactions to the unusual and unexpected situation of the COVID-19 pandemic. Therefore, the project was largely exploratory in nature. Interviews with the participants at different stages of the epidemic allowed us to see a wide spectrum of problems and ways of dealing with them. The conducted study had three main research questions:

• What are the biggest challenges connected to the COVID-19 pandemic and the resulting restrictions?
• How are people dealing with the pandemic challenges?
• What are the ways of coping with the restrictions resulting from a pandemic change as it continues and develops (perspective of first 6 months)?

The study was approved by the institutional review board of the Faculty of Psychology University of Warsaw, Poland. All participants were provided written and oral information about the study, which included that participation was voluntary, that it was possible to withdraw without any consequences at any time, and the precautions that would be taken to protect data confidentiality. Informed consent was obtained from all participants. To ensure confidentiality, quotes are presented only with gender, age, and family status.

The study was based on qualitative methodology: individual in-depth interviews, s which are the appropriate to approach a new and unknown and multithreaded topic which, at the beginning of 2020, was the COVID-19 pandemic. Due to the need to observe respondents’ reactions to the dynamically changing situation of the COVID-19 pandemic, longitudinal study was used where the moderator met on-line with the same respondent several times, at specific time intervals. A longitudinal study was used to capture the changes in opinions, emotions, and behaviors of the respondents resulting from the changes in the external circumstances (qualitative in-depth interview tracking–[ 34 ]).

The study took place from the end of March to October 2020. Due to the epidemiological situation in the country interviews took place online, using the Google Meets online video platform. The audio was recorded and then transcribed. Before taking part in the project, the respondents were informed about the purpose of the study, its course, and the fact that participation in the project is voluntary, and that they will be able to withdraw from participation at any time. The respondents were not paid for taking part in the project.

Participants.

In total, 115 interviews were conducted with 20 participants (6 interviews with the majority of respondents). Two participants (number 11 and 19, S2 Table ) dropped out of the last two interviews, and one (number 6) dropped out of the last interview. The study was based on a purposive sample and the respondents differed in gender, age, education, family status, and work situation (see S2 Table ). In addition to demographic criteria intended to ensure that the sample was as diverse as possible, an additional criterion was to have a permanent Internet connection and a computer capable of online video interviewing. Study participants were recruited using the snowball method. They were distant acquaintances of acquaintances of individuals involved in the study. None of the moderators knew their interviewees personally.

A total of 10 men and 10 women participated in the study; their age range was: 25–55; the majority had higher education (17 respondents), they were people with different professions and work status, and different family status (singles, couples without children, and families with children). Such diversity of respondents allowed us to obtain information from different life perspectives. A full description of characteristics of study participants can be found in S2 Table .

Each interview took 2 hours on average, which gives around 240 hours of interviews. Subsequent interviews with the same respondents conducted at different intervals resulted from the dynamics of the development of the pandemic and the restrictions introduced in Poland by the government.

The interviews scenario took a semi-structured form. This allowed interviewers freely modify the questions and topics depending on the dynamics of the conversation and adapt the subject matter of the interviews not only to the research purposes but also to the needs of a given respondent. The interview guides were modified from week to week, taking into account the development of the epidemiological situation, while at the same time maintaining certain constant parts that were repeated in each interview. The main parts of the interview topic guide consisted of: (a) experiences from the time of previous interviews: thoughts, feeling, fears, and hopes; (b) everyday life—organization of the day, work, free time, shopping, and eating, etc.; (c) changes—what had changed in the life of the respondent from the time of the last interview; (d) ways of coping with the situation; and (e) media—reception of information appearing in the media. Additionally, in each interview there were specific parts, such as the reactions to the beginning of the pandemic in the first interview or the reaction to the specific restrictions that were introduced.

The interviews were conducted by 5 female interviewers with experience in moderating qualitative interviews, all with a psychological background. After each series of interviews, all the members of the research teams took part in debriefing sessions, which consisted of discussing the information obtained from each respondent, exchanging general conclusions, deciding about the topics for the following interview stage, and adjusting them to the pandemic situation in the country.

Data analysis.

All the interviews were transcribed in Polish by the moderators and then double-checked (each moderator transcribed the interviews of another moderator, and then the interviewer checked the accuracy of the transcription). The whole process of analysis was conducted on the material in Polish (the native language of the authors of the study and respondents). The final page count of the transcript is approximately 1800 pages of text. The results presented below are only a portion of the total data collected during the interviews. While there are about 250 pages of the transcription directly related to the topic of the article, due to the fact that the interview was partly free-form, some themes merge with others and it is not possible to determine the exact number of pages devoted exclusively to analysis related to the topic of the article. Full dataset can be found in S1 Dataset .

Data was then processed into thematic analysis, which is defined as a method of developing qualitative data consisting of the identification, analysis, and description of the thematic areas [ 35 ]. In this type of analysis, a thematic unit is treated as an element related to the research problem that includes an important aspect of data. An important advantage of thematic analysis is its flexibility, which allows for the adoption of the most appropriate research strategy to the phenomenon under analysis. An inductive approach was used to avoid conceptual tunnel vision. Extracting themes from the raw data using an inductive approach precludes the researcher from imposing a predetermined outcome.

As a first step, each moderator reviewed the transcripts of the interviews they had conducted. Each transcript was thematically coded individually from this point during the second and the third reading. In the next step, one of the researchers reviewed the codes extracted by the other members of the research team. Then she made initial interpretations by generating themes that captured the essence of the previously identified codes. The researcher created a list of common themes present in all of the interviews. In the next step, the extracted themes were discussed again with all the moderators conducting the coding in order to achieve consistency. This collaborative process was repeated several times during the analysis. Here, further superordinate (challenges of COVID-19 pandemic) and subordinate (ways of dealing with challenges) themes were created, often by collapsing others together, and each theme listed under a superordinate and subordinate category was checked to ensure they were accurately represented. Through this process of repeated analysis and discussion of emerging themes, it was possible to agree on the final themes that are described below.

Main challenges of the COVID-19 pandemic.

Challenge 1 –limitation of direct contact with people . The first major challenge of the pandemic was that direct contact with other people was significantly reduced. The lockdown forced many people to work from home and limit contact not only with friends but also with close family (parents, children, and siblings). Limiting contact with other people was a big challenge for most of our respondents, especially those who were living alone and for those who previously led an active social life. Depending on their earlier lifestyle profile, for some, the bigger problem was the limitation of contact with the family, for others with friends, and for still others with co-workers.

I think that because I can’t meet up with anyone and that I’m not in a relationship , I miss having sex , and I think it will become even more difficult because it will be increasingly hard to meet anyone . (5 . 3_ M_39_single) . The number In the brackets at the end of the quotes marks the respondent’s number (according to Table 1 ) and the stage of the interview (after the dash), further is information about gender (F/M), age of the respondent and family status. Linguistic errors in the quotes reflect the spoken language of the respondents.

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https://doi.org/10.1371/journal.pone.0258133.t001

Changes over time . Over the course of the 6 months of the study, an evolution in the attitudes to the restriction of face-to-face contact could be seen: from full acceptance, to later questioning its rationale. Initially (March and April), almost all the respondents understood the reasons for the isolation and were compliant. At the beginning, people were afraid of the unknown COVID-19. They were concerned that the tragic situation from Italy, which was intensively covered in the media, could repeat itself in Poland (stage 1–2 of the study). However, with time, the isolation started to bother them more and more, and they started to look for solutions to bypass the isolation guidelines (stage 3–4), both real (simply meeting each other) and mental (treating isolation only as a guideline and not as an order, perceiving the family as being less threatening than acquaintances or strangers in a store). The turning point was the long May weekend that, due to two public holidays (1 st and 3 rd May), has for many years been used as an opportunity to go away with family or friends. Many people broke their voluntary isolation during that time encouraged by information about the coming loosening of restrictions.

During the summer (stage 5 of the survey), practically no one was fully compliant with the isolation recommendations anymore. At that time, a growing familiarity could be observed with COVID-19 and an increasing tendency to talk about it as “one of many diseases”, and to convince oneself that one is not at risk and that COVID-19 is no more threatening than other viruses. Only a small group of people consciously failed to comply with the restrictions of contact with others from the very beginning of the pandemic. This behavior was mostly observed among people who were generally less anxious and less afraid of COVID-19.

I’ve had enough. I’ve had it with sitting at home. Okay, there’s some kind of virus, it’s as though it’s out there somewhere; it’s like I know 2 people who were infected but they’re still alive, nothing bad has happened to anyone. It’s just a tiny portion of people who are dying. And is it really such a tragedy that we have to be locked up at home? Surely there’s an alternative agenda there? (17.4_F_35_Adult and child)

Ways of dealing . In the initial phase, when almost everyone accepted this restriction and submitted to it, the use of communication platforms for social meetings increased (see Ways of dealing with challenges in Table 1 ) . Meetings on communication platforms were seen as an equivalent of the previous face-to-face contact and were often even accompanied by eating or drinking alcohol together. However, over time (at around stage 4–5 of the study) people began to feel that such contact was an insufficient substitute for face-to-face meetings and interest in online meetings began to wane. During this time, however, an interesting phenomenon could be seen, namely, that for many people the family was seen as a safer environment than friends, and definitely safer than strangers. The belief was that family members would be honest about being sick, while strangers not necessarily, and—on an unconscious level—the feeling was that the “family is safe”, and the “family can’t hurt them”.

When it became clear that online communication is an insufficient substitute for face-to-face contacts, people started to meet up in real life. However, a change in many behaviors associated with meeting people is clearly visible, e.g.: refraining from shaking hands, refraining from cheek kissing to greet one another, and keeping a distance during a conversation.

I can’t really say that I could ‘feel’ Good Friday or Holy Saturday. On Sunday, we had breakfast together with my husband’s family and his sister. We were in three different places but we connected over Skype. Later, at noon, we had some coffee with my parents, also over Skype. It’s obvious though that this doesn’t replace face-to-face contact but it’s always some form of conversation. (9.3_F_25_Couple, no children)

Challenge 2 –restrictions on movement and travel . In contrast to the restrictions on contact with other people, the restrictions on movement and the closing of borders were perceived more negatively and posed bigger challenges for some people (especially those who used to do a lot of travelling). In this case, it was less clear why these regulations were introduced (especially travel restrictions within the country). Moreover, travel restrictions, particularly in the case of international travels, were associated with a limitation of civil liberties. The limitation (or complete ban) on travelling abroad in the Polish situation evoked additional connotations with the communist times, that is, with the fact that there was no freedom of movement for Polish citizens (associations with totalitarianism and dictatorship). Interestingly, the lack of acceptance of this restriction was also manifested by people who did not travel much. Thus, it was not just a question of restricting travelling abroad but more of restricting the potential opportunity (“even if I’m not planning on going anywhere, I know I still can”).

Limitations on travelling around the country were particularly negatively felt by families with children, where parents believe that regular exercise and outings are necessary for the proper development of their children. For parents, it was problematic to accept the prohibition of leaving the house and going to the playground (which remained closed until mid-May). Being outdoors was perceived as important for maintaining immunity (exercise as part of a healthy lifestyle), therefore, people could not understand the reason underlying this restriction and, as a consequence, often did not accept it.

I was really bothered by the very awareness that I can’t just jump in my car or get on a plane whenever I want and go wherever I want. It’s not something that I have to do on a daily basis but freedom of movement and travelling are very important for me. (14.2_M_55_Two adults and children)

Changes over time . The travel and movement limitations, although objectively less severe for most people, aroused much greater anger than the restrictions on social contact. This was probably due to a greater sense of misunderstanding as to why these rules were being introduced in the first place. Moreover, they were often communicated inconsistently and chaotically (e.g., a ban on entering forests was introduced while, at the same time, shopping malls remained open and masses were allowed to attend church services). This anger grew over time—from interview to interview, the respondents’ irritation and lack of acceptance of this was evident (culminating in the 3 rd -4 th stage of the study). The limitation of mobility was also often associated with negative consequences for both health and the economy. Many people are convinced that being in the open air (especially accompanied by physical activity) strengthens immunity, therefore, limiting such activity may have negative health consequences. Some respondents pointed out that restricting travelling, the use of hotels and restaurants, especially during the holiday season, will have serious consequences for the existence of the tourism industry.

I can’t say I completely agree with these limitations because it’s treating everything selectively. It’s like the shopping mall is closed, I can’t buy any shoes but I can go to a home improvement store and buy some wallpaper for myself. So I don’t see the difference between encountering people in a home improvement store and a shopping mall. (18.2_F_48_Two adults and children)

Ways of dealing . Since the restriction of movement and travel was more often associated with pleasure-related behaviors than with activities necessary for living, the compensations for these restrictions were usually also from the area of hedonistic behaviors. In the statements of our respondents, terms such as “indulging” or “rewarding oneself” appeared, and behaviors such as throwing small parties at home, buying better alcohol, sweets, and new clothes were observed. There were also increased shopping behaviors related to hobbies (sometimes hobbies that could not be pursued at the given time)–a kind of “post-pandemic” shopping spree (e.g., a new bike or new skis).

Again, the reaction to this restriction also depended on the level of fear of the COVID-19 disease. People who were more afraid of being infected accepted these restrictions more easily as it gave them the feeling that they were doing something constructive to protect themselves from the infection. Conversely, people with less fears and concerns were more likely to rebel and break these bans and guidelines.

Another way of dealing with this challenge was making plans for interesting travel destinations for the post-pandemic period. This was especially salient in respondents with an active lifestyle in the past and especially visible during the 5 th stage of the study.

Today was the first day when I went to the store (due to being in quarantine after returning from abroad). I spent loads of money but I normally would have never spent so much on myself. I bought sweets and confectionery for Easter time, some Easter chocolates, too. I thought I’d do some more baking so I also bought some ingredients to do this. (1.2_ F_25_single)

Challenge 3 –necessary change in active lifestyle . Many of the limitations related to COVID-19 were a challenge for people with an active lifestyle who would regularly go to the cinema, theater, and gym, use restaurants, and do a lot of travelling. For those people, the time of the COVID constraints has brought about huge changes in their lifestyle. Most of their activities were drastically restricted overnight and they suddenly became domesticated by force, especially when it was additionally accompanied by a transition to remote work.

Compulsory spending time at home also had serious consequences for people with school-aged children who had to confront themselves with the distance learning situation of their children. The second challenge for families with children was also finding (or helping find) activities for their children to do in their free time without leaving the house.

I would love to go to a restaurant somewhere. We order food from the restaurant at least once a week, but I’d love to go to the restaurant. Spending time there is a different way of functioning. It is enjoyable and that is what I miss. I would also go to the cinema, to the theater. (13.3_M_46_Two adults and child.)

Changes over time . The nuisance of restrictions connected to an active lifestyle depended on the level of restrictions in place at a given time and the extent to which a given activity could be replaced by an alternative. Moreover, the response to these restrictions depended more on the individual differences in lifestyle rather than on the stage of the interview (except for the very beginning, when the changes in lifestyle and everyday activities were very sudden).

I miss that these restaurants are not open . And it’s not even that I would like to eat something specific . It is in all of this that I miss such freedom the most . It bothers me that I have no freedom . And I am able to get used to it , I can cook at home , I can order from home . But I just wish I had a choice . (2 . 6_F_27_single ).

Ways of dealing . In the initial phase of the pandemic (March-April—stage 1–3 of the study), when most people were afraid of the coronavirus, the acceptance of the restrictions was high. At the same time, efforts were made to find activities that could replace existing ones. Going to the gym was replaced by online exercise, and going to the cinema or theater by intensive use of streaming platforms. In the subsequent stages of the study, however, the respondents’ fatigue with these “substitutes” was noticeable. It was then that more irritation and greater non-acceptance of certain restrictions began to appear. On the other hand, the changes or restrictions introduced during the later stages of the pandemic were less sudden than the initial ones, so they were often easier to get used to.

I bought a small bike and even before that we ordered some resistance bands to work out at home, which replace certain gym equipment and devices. […] I’m considering learning a language. From the other online things, my girlfriend is having yoga classes, for instance. (7.2_M_28_Couple, no children)

Challenge 4 –boredom , monotony . As has already been shown, for many people, the beginning of the pandemic was a huge change in lifestyle, an absence of activities, and a resulting slowdown. It was sometimes associated with a feeling of weariness, monotony, and even of boredom, especially for people who worked remotely, whose days began to be similar to each other and whose working time merged with free time, weekdays with the weekends, and free time could not be filled with previous activities.

In some way, boredom. I can’t concentrate on what I’m reading. I’m trying to motivate myself to do such things as learning a language because I have so much time on my hands, or to do exercises. I don’t have this balance that I’m actually doing something for myself, like reading, working out, but also that I’m meeting up with friends. This balance has gone, so I’ve started to get bored with many things. Yesterday I felt that I was bored and something should start happening. (…) After some time, this lack of events and meetings leads to such immense boredom. (1.5_F_25_single)

Changes over time . The feeling of monotony and boredom was especially visible in stage 1 and 2 of the study when the lockdown was most restrictive and people were knocked out of their daily routines. As the pandemic continued, boredom was often replaced by irritation in some, and by stagnation in others (visible in stages 3 and 4 of the study) while, at the same time, enthusiasm for taking up new activities was waning. As most people were realizing that the pandemic was not going to end any time soon, a gradual adaptation to the new lifestyle (slower and less active) and the special pandemic demands (especially seen in stage 5 and 6 of the study) could be observed.

But I see that people around me , in fact , both family and friends , are slowly beginning to prepare themselves for more frequent stays at home . So actually more remote work , maybe everything will not be closed and we will not be locked in four walls , but this tendency towards isolation or self-isolation , such a deliberate one , appears . I guess we are used to the fact that it has to be this way . (15 . 6_M_43_Two adults and child) .

Ways of dealing . The answer to the monotony of everyday life and to finding different ways of separating work from free time was to stick to certain rituals, such as “getting dressed for work”, even when work was only by a computer at home or, if possible, setting a fixed meal time when the whole family would gather together. For some, the time of the beginning of the pandemic was treated as an extra vacation. This was especially true of people who could not carry out their work during the time of the most severe restrictions (e.g., hairdressers and doctors). For them, provided that they believed that everything would return to normal and that they would soon go back to work, a “vacation mode” was activated wherein they would sleep longer, watch a lot of movies, read books, and generally do pleasant things for which they previously had no time and which they could now enjoy without feeling guilty. Another way of dealing with the monotony and transition to a slower lifestyle was taking up various activities for which there was no time before, such as baking bread at home and cooking fancy dishes.

I generally do have a set schedule. I begin work at eight. Well, and what’s changed is that I can get up last minute, switch the computer on and be practically making my breakfast and coffee during this time. I do some work and then print out some materials for my younger daughter. You know, I have work till four, I keep on going up to the computer and checking my emails. (19.1_F_39_Two adults and children)

Challenge 5 –uncertainty about the future . Despite the difficulties arising from the circumstances and limitations described above, it seems that psychologically, the greatest challenge during a pandemic is the uncertainty of what will happen next. There was a lot of contradictory information in the media that caused a sense of confusion and heightened the feeling of anxiety.

I’m less bothered about the changes that were put in place and more about this concern about what will happen in the future. Right now, it’s like there’s these mood swings. […] Based on what’s going on, this will somehow affect every one of us. And that’s what I’m afraid of. The fact that someone will not survive and I have no way of knowing who this could be—whether it will be me or anyone else, or my dad, if somehow the coronavirus will sneak its way into our home. I simply don’t know. I’m simply afraid of this. (10.1_F_55_Couple, no children)

Changes over time . In the first phase of the pandemic (interviews 1–3), most people felt a strong sense of not being in control of the situation and of their own lives. Not only did the consequences of the pandemic include a change in lifestyle but also, very often, the suspension of plans altogether. In addition, many people felt a strong fear of the future, about what would happen, and even a sense of threat to their own or their loved ones’ lives. Gradually (interview 4), alongside anxiety, anger began to emerge about not knowing what would happen next. At the beginning of the summer (stage 5 of the study), most people had a hope of the pandemic soon ending. It was a period of easing restrictions and of opening up the economy. Life was starting to look more and more like it did before the pandemic, fleetingly giving an illusion that the end of the pandemic was “in sight” and the vision of a return to normal life. Unfortunately, autumn showed that more waves of the pandemic were approaching. In the interviews of the 6 th stage of the study, we could see more and more confusion and uncertainty, a loss of hope, and often a manifestation of disagreement with the restrictions that were introduced.

This is making me sad and angry. More angry, in fact. […] I don’t know what I should do. Up until now, there was nothing like this. Up until now, I was pretty certain of what I was doing in all the decisions I was making. (14.4_M_55_Two adults and children)

Ways of dealing . People reacted differently to the described feeling of insecurity. In order to reduce the emerging fears, some people searched (sometimes even compulsively) for any information that could help them “take control” of the situation. These people searched various sources, for example, information on the number of infected persons and the number of deaths. This knowledge gave them the illusion of control and helped them to somewhat reduce the anxiety evoked by the pandemic. The behavior of this group was often accompanied by very strict adherence to all guidelines and restrictions (e.g., frequent hand sanitization, wearing a face mask, and avoiding contact with others). This behavior increased the sense of control over the situation in these people.

A completely opposite strategy to reducing the feeling of uncertainty which we also observed in some respondents was cutting off information in the media about the scale of the disease and the resulting restrictions. These people, unable to keep up with the changing information and often inconsistent messages, in order to maintain cognitive coherence tried to cut off the media as much as possible, assuming that even if something really significant had happened, they would still find out.

I want to keep up to date with the current affairs. Even if it is an hour a day. How is the pandemic situation developing—is it increasing or decreasing. There’s a bit of propaganda there because I know that when they’re saying that they have the situation under control, they can’t control it anyway. Anyhow, it still has a somewhat calming effect that it’s dying down over here and that things aren’t that bad. And, apart from this, I listen to the news concerning restrictions, what we can and can’t do. (3.1_F_54_single)

Discussion and conclusions

The results of our study showed that the five greatest challenges resulting from the COVID-19 pandemic are: limitations of direct contact with people, restrictions on movement and travel, change in active lifestyle, boredom and monotony, and finally uncertainty about the future. As we can see the spectrum of problems resulting from the pandemic is very wide and some of them have an impact on everyday functioning and lifestyle, some other influence psychological functioning and well-being. Moreover, different people deal with these problems differently and different changes in everyday life are challenging for them. The first challenge of the pandemic COVID-19 problem is the consequence of the limitation of direct contact with others. This regulation has very strong psychological consequences in the sense of loneliness and lack of closeness. Initially, people tried to deal with this limitation through the use of internet communicators. It turned out, however, that this form of contact for the majority of people was definitely insufficient and feelings of deprivation quickly increased. As much data from psychological literature shows, contact with others can have great psychological healing properties [e.g., 29 ]. The need for closeness is a natural need in times of crisis and catastrophes [ 30 ]. Unfortunately, during the COVID-19 pandemic, the ability to meet this need was severely limited by regulations. This led to many people having serious problems with maintaining a good psychological condition.

Another troubling limitation found in our study were the restrictions on movement and travel, and the associated restrictions of most activities, which caused a huge change in lifestyle for many people. As shown in previous studies, travel and diverse leisure activities are important predictors of greater well-being [ 36 ]. Moreover, COVID-19 pandemic movement restrictions may be perceived by some people as a threat to human rights [ 37 ], which can contribute to people’s reluctance to accept lockdown rules.

The problem with accepting these restrictions was also related to the lack of understanding of the reasons behind them. Just as the limitation in contact with other people seemed understandable, the limitations related to physical activity and mobility were less so. Because of these limitations many people lost a sense of understanding of the rules and restrictions being imposed. Inconsistent communication in the media—called by some researchers the ‘infodemic’ [ 18 ], as well as discordant recommendations in different countries, causing an increasing sense of confusion in people.

Another huge challenge posed by the current pandemic is the feeling of uncertainty about the future. This feeling is caused by constant changes in the rules concerning daily functioning during the pandemic and what is prohibited and what is allowed. People lose their sense of being in control of the situation. From the psychological point of view, a long-lasting experience of lack of control can cause so-called learned helplessness, a permanent feeling of having no influence over the situation and no possibility of changing it [ 38 ], which can even result in depression and lower mental and physical wellbeing [ 39 ]. Control over live and the feeling that people have an influence on what happens in their lives is one of the basic rules of crisis situation resilience [ 30 ]. Unfortunately, also in this area, people have huge deficits caused by the pandemic. The obtained results are coherent with previous studies regarding the strategies harnessed to cope with the pandemic [e.g., 5 , 10 , 28 , 33 ]. For example, some studies showed that seeking social support is one of the most common strategies used to deal with the coronavirus pandemic [ 33 , 40 ]. Other ways to deal with this situation include distraction, active coping, and a positive appraisal of the situation [ 41 ]. Furthermore, research has shown that simple coping behaviors such as a healthy diet, not reading too much COVID-19 news, following a daily routine, and spending time outdoors may be protective factors against anxiety and depressive symptoms in times of the coronavirus pandemic [ 41 ].

This study showed that the acceptance of various limitations, and especially the feeling of discomfort associated with them, depended on the person’s earlier lifestyle. The more active and socializing a person was, the more restrictions were burdensome for him/her. The second factor, more of a psychological nature, was the fear of developing COVID-19. In this case, people who were more afraid of getting sick were more likely to submit to the imposed restrictions that, paradoxically, did not reduce their anxiety, and sometimes even heightened it.

Limitations of the study.

While the study shows interesting results, it also has some limitations. The purpose of the study was primarily to capture the first response to problems resulting from a pandemic, and as such its design is not ideal. First, the study participants are not diverse as much as would be desirable. They are mostly college-educated and relatively well off, which may influence how they perceive the pandemic situation. Furthermore, the recruitment was done by searching among the further acquaintances of the people involved in the study, so there is a risk that all the people interviewed come from a similar background. It would be necessary to conduct a study that also describes the reaction of people who are already in a more difficult life situation before the pandemic starts.

Moreover, it would also be worthwhile to pay attention to the interviewers themselves. All of the moderators were female, and although gender effects on the quality of the interviews and differences between the establishment of relationships between women and men were not observed during the debriefing process, the topic of gender effects on the results of qualitative research is frequently addressed in the literature [ 42 , 43 ]. Although the researchers approached the process with reflexivity and self-criticism at all stages, it would have seemed important to involve male moderators in the study to capture any differences in relationship dynamics.

Practical implications.

The study presented has many practical implications. Decision-makers in the state can analyze the COVID-19 pandemic crisis in a way that avoids a critical situation involving other infectious diseases in the future. The results of our study showing the most disruptive effects of the pandemic on people can serve as a basis for developing strategies to deal with the effects of the crisis so that it does not translate into a deterioration of the public’s mental health in the future.

The results of our study can also provide guidance on how to communicate information about restrictions in the future so that they are accepted and respected (for example by giving rational explanations of the reasons for introducing particular restrictions). In addition, the results of our study can also be a source of guidance on how to deal with the limitations that may arise in a recurrent COVID-19 pandemic, as well as other emergencies that could come.

The analysis of the results showed that the COVID-19 pandemic, and especially the lockdown periods, are a particular challenge for many people due to reduced social contact. On the other hand, it is social contacts that are at the same time a way of a smoother transition of crises. This knowledge should prompt decision-makers to devise ways to ensure pandemic safety without drastically limiting social contacts and to create solutions that give people a sense of control (instead of depriving it of). Providing such solutions can reduce the psychological problems associated with a pandemic and help people to cope better with it.

Conclusions

As more and more is said about the fact that the COVID-19 pandemic may not end soon and that we are likely to face more waves of this disease and related lockdowns, it is very important to understand how the different restrictions are perceived, what difficulties they cause and what are the biggest challenges resulting from them. For example, an important element of accepting the restrictions is understanding their sources, i.e., what they result from, what they are supposed to prevent, and what consequences they have for the fight against the pandemic. Moreover, we observed that the more incomprehensible the order was, the more it provoked to break it. This means that not only medical treatment is extremely important in an effective fight against a pandemic, but also appropriate communication.

The results of our study showed also that certain restrictions cause emotional deficits (e.g., loneliness, loss of sense of control) and, consequently, may cause serious problems with psychological functioning. From this perspective, it seems extremely important to understand which restrictions are causing emotional problems and how they can be dealt with in order to reduce the psychological discomfort associated with them.

Supporting information

S1 table. a full description of the changes occurring in poland at the time of the study..

https://doi.org/10.1371/journal.pone.0258133.s001

S2 Table. Characteristics of study participants.

https://doi.org/10.1371/journal.pone.0258133.s002

S1 Dataset. Transcriptions from the interviews.

https://doi.org/10.1371/journal.pone.0258133.s003

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COVID-19 vaccines: implementation, limitations and opportunities

Affiliation.

• 1 University of California San Diego, Distinguished Professor of Pathology and Medicine (Active Emeritus); Director, The HIV Institute; Co- Director, San Diego Center for AIDS Research; Florence Seeley Riford Emeritus Chair in AIDS Research, CA, USA.
• PMID: 33688588
• PMCID: PMC7936373
• DOI: 10.35772/ghm.2021.01010

The speed of development and the magnitude of efficacy of recently developed vaccines directed against SARS-CoV-2 has been truly remarkable. This editorial will not summarize the highly publicized and reviewed information about the design and clinical trial results of these vaccines. Rather, I will speculate about several issues regarding i ) considerations of the rollout and implementation of the multiple vaccines, ii ) the use of the vaccines in ways different from those used in the registrational phase 3 studies, iii ) the future both of SARS-CoV-2 in the human population and of "normal" human life returning after widespread vaccination, and iv ) the implications of the success of these SARS-CoV-2 vaccines for vaccine development against other pathogens.

Keywords: COVID-19; SARS-CoV-2; vaccine.

2021, National Center for Global Health and Medicine.

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Conflict of interest statement

The author has no conflict of interest to disclose.

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Methodological limitations in studies assessing the effects of environmental and socioeconomic variables on the spread of COVID-19: a systematic review

• Maria A. Barceló 1 , 2 &
• Marc Saez   ORCID: orcid.org/0000-0003-1882-0157 1 , 2  

Environmental Sciences Europe volume  33 , Article number:  108 ( 2021 ) Cite this article

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While numerous studies have assessed the effects of environmental (meteorological variables and air pollutants) and socioeconomic variables on the spread of the COVID-19 pandemic, many of them, however, have significant methodological limitations and errors that could call their results into question. Our main objective in this paper is to assess the methodological limitations in studies that evaluated the effects of environmental and socioeconomic variables on the spread of COVID-19.

We carried out a systematic review by conducting searches in the online databases PubMed, Web of Science and Scopus up to December 31, 2020. We first excluded those studies that did not deal with SAR-CoV-2 or COVID-19, preprints, comments, opinion or purely narrative papers, reviews and systematic literature reviews. Among the eligible full-text articles, we then excluded articles that were purely descriptive and those that did not include any type of regression model. We evaluated the risk of bias in six domains: confounding bias, control for population, control of spatial and/or temporal dependence, control of non-linearities, measurement errors and statistical model. Of the 5631 abstracts initially identified, we were left with 132 studies on which to carry out the qualitative synthesis. Of the 132 eligible studies, we evaluated 63.64% of the studies as high risk of bias, 19.70% as moderate risk of bias and 16.67% as low risk of bias.

Conclusions

All the studies we have reviewed, to a greater or lesser extent, have methodological limitations. These limitations prevent conclusions being drawn concerning the effects environmental (meteorological and air pollutants) and socioeconomic variables have had on COVID-19 outcomes. However, we dare to argue that the effects of these variables, if they exist, would be indirect, based on their relationship with social contact.

Numerous studies have assessed the effects of environmental and socioeconomic variables on the spread of the COVID-19 pandemic. Most of them have addressed the influence meteorological variables have, although there are also quite a few that have considered the effects of air pollutants and socioeconomic variables. Those which assessed the effects of meteorological variables were the first to appear, specifically between the last week of March and the first week of April 2020. In other words, very close to COVID-19 being officially declared a global pandemic (11 March 2020) [ 1 ]. Later, there were those which evaluated the effects of air pollutants, the first of which appeared between the end of April and the first week of May 2020. Finally, the last ones to appear were those related to socioeconomic variables; the first of which was mid-May 2020.

The studies differ in their outcomes (new and cumulative cases, mortality, reproductive number, etc.), study populations (the world, countries, regions, cities), confounders as well as in the way of controlling for them, and in the modelling strategies adopted. However, with the exception of socioeconomic variables, several systematic reviews attempting to synthesize the evidence have already been published.

For instance, with regard to meteorological variables, Mecenas et al. carried out a bibliographic search until the end of March 2020 [ 2 ]. In reviewing 17 studies (most of them preprints), they found that warm wet climates seemed to reduce the spread of COVID-19. However, the role of temperature and humidity on the spread of the virus was very moderate, since these variables alone could not explain most of the variability in the disease’s transmission. Smit et al., in a systematic review carried out in July 2020 (that is, of studies that used data from the first wave), critically evaluated 42 articles published in scientific journals and 80 preprints [ 3 ]. They concluded that the evidence suggested that either there was no modulating effect of the summer weather conditions (i.e., high temperature and low humidity reduce the transmission rate of the virus) or, along the same lines as Mecenas et al., if it did exist, it was weak. Smit et al. also found similar results for other meteorological variables, such as ultraviolet radiation and wind speed [ 3 ]. McClymont and Hu discussed 23 articles with moderate or high ratings (out a total of 86 eligible peer-reviewed articles) published until October 1 (also contemplating only the first wave) [ 4 ], and found that temperature and humidity were associated with COVID-19 incidence. However, while the decrease in temperature was associated with increases in incidence, in the variations in humidity the results were mixed (positive and negative associations were found). They also found that wind speed and rainfall results were not consistent across studies [ 4 ].

In relation to air pollutants, Copat et al. carried out a systematic review of 15 studies (13 articles and 2 preprints) published between April 2020 and July 6th, 2020 [ 5 ]. They found a consistent association between some air pollutants (fine particles, PM 2.5 with a diameter of 2.5 microns (μm) or less, and nitrogen dioxide, NO 2 , and with a less extent coarse particles, PM 10, with a diameter of 10 μm or less) and a higher incidence and mortality from COVID-19. They pointed out, however, that there were important limitations for any direct comparison of the results and that more studies were needed to strengthen scientific evidence. Malecki et al. carried out a systematic review of 19 studies, published through to October 31, 2020, that assessed the association of particulate matter (i.e., PM 10 and PM 2.5 ) pollution and the spread of SARS-CoV-2 [ 6 ]. They pointed out that although there were suggestions that particulate matter (PM) played a role in the spread of SARS-CoV-2, PM concentration alone cannot be effective in spreading the COVID-19 disease, and that other meteorological and environmental variables were also involved.

Until today (June 2021), no peer-reviewed systematic reviews have been published concerning the influence socioeconomic variables have on the spread of the pandemic. However, let us advance some of our results here by noting that in ecological studies the results were not conclusive. In some, especially those carried out in the United States, the areas with greater economic deprivation had a higher incidence and also a higher mortality. That said, in others no association was found, or deprivation was even found to be a protective factor. What was consistently observed was the fact that the higher the population density was, the greater incidence and mortality were. In individual studies, however, individuals with lower incomes or from more disadvantaged groups were at greater risk of hospitalization and death.

Nevertheless, all the reviews state that many of the studies have significant methodological limitations and errors that could bring their results into question. Our main objective here is to assess the methodological limitations in the studies that evaluated the effects environmental and socioeconomic variables have had on the spread of COVID-19. Furthermore, we discuss the results of those studies that were, in fact, able to control those very limitations.

Systematic review

The protocol for this review is registered in the Prospective Register of Systematic Reviews (PROSPERO 2020 CRD42020201540). In the review process, we followed the preferred reporting items for systematic reviews and meta-analysis (PRISMA) protocols [ 7 ]. The literature search, study selection, data extraction, and quality assessment were performed by each of us independently. In case of any discrepancy between us, we all reached an agreement on the final decision.

By combining the keyword ‘COVID-19’ with the keywords ‘temperature’, ‘(meteorological variables)’, ‘(air pollutants)’, ‘(environmental variables)’, and ‘(socioeconomic variables)’, through the Boolean connector ‘AND’ we conducted a search in the online databases PubMed, Web of Science and Scopus, up to December 31, 2020. We did not impose any language restrictions, nor did we contact any author for additional information.

All the articles retrieved underwent an initial title and abstract screening, where any duplicates were discarded, followed by a full-text screening for eligible abstracts. We made a first exclusion of those studies that did not deal with SARS-CoV-2 or COVID-19, preprints (non-peer-reviewed articles), comments, opinion or purely narrative papers, reviews and systematic literature reviews (Fig.  1 ). Among the eligible full-text articles, we made a second exclusion of those articles that were purely descriptive (including only plots or maps, etc.) and those that did not include any type of regression model (those that only included the analysis of correlations, for example).

Flow-chart of the study selection process

We extracted the following data from the articles included in the qualitative analysis: first author, study population, study period, outcome, explanatory variables, covariates, the statistical method (including the model specification and the methods to control the confounding), and the study findings.

Methodological limitations

The usual assessment tools for observational studies were not entirely suitable for assessing the risk of bias of the studies we reviewed. We preferred to adapt the tool proposed by Parmar et al. [ 8 ] who, in turn, adapted the Newcastle–Ottawa scale [ 9 ] and the RTI item bank [ 10 ]. Specifically, we used six domains: two from Parmar et al. [ 8 ]—confounding bias and measurement errors in the outcome and/or in the exposure variables; one based on the dimension ‘unobserved confounding’ in Saez et al. [ 11 ]—control of the spatial and/or the temporal dependence; and three that we added ex novo in this paper—control for the population, statistical model, and control of non-linearities.

In each study, each of the six domains were rated as: 1—low risk of bias, 2—moderate risk of bias, or 3—high risk of bias) (Table 1 ). For the overall rating of each study, we evaluated it as 'strong' (low risk of bias) if, at most, one of the six domains was rated as high risk of bias (i.e., a rating of 3), 'moderate' (moderate risk of bias) if up to two domains were rated as weak, or 'weak' (high risk of bias) if three or more domains were rated as high risk of bias. For the rating of both the domains and the studies, we rely on Parmar et al. [ 8 ].

Three of the six dimensions corresponded to the specification error known as omission of relevant variables: confounding bias, control of the population and control of the spatial and/or of the temporal dependence. This specification error leads to biased and inconsistent estimators (that is, the estimators biased even asymptotically, i.e., when the number of observations is very high) and, in addition, the variances of the estimators are also misleading [ 12 ]. In any case, the inference of those studies that do not control for this error is highly compromised.

Confounding bias

None of the studies included all possible confounders, especially if the studies were ecological (as most of them were). However, as regards the spread of COVID-19, there is a confounder that, at a minimum, must be controlled for, namely, social contact.

The main route of transmission for COVID-19 is through the direct or indirect contact with an infected subject via the small droplets that occur when they cough or sneeze [ 13 ]. Thus, this contact must be controlled for in the models, even if indirectly. The control, although partial, can be carried out through mobility or, much more indirectly, through socioeconomic variables. In general, greater mobility implies greater levels of contact. Likewise, areas with high population densities are known to have greater social contact. Furthermore, some occupations present a greater risk, particularly those that were less able to switch to teleworking and, therefore, require greater mobility and the resulting higher level of social contact.

Unobserved confounding (i.e., residual confounding) including, for example, random effects that capture heterogeneity, should also be controlled for. In other words, unobserved variables specific to the unit of analysis (area or individual) that could influence the risk of, in this case, the spread of the COVID-19.

We scored this domain with a 3 if the confounding was not controlled for by any method, with a 2 if the observed confounding was controlled for with a moderate number of confounders (up to two maximum), in particular mobility or socioeconomic variables, or with a 1 if the observed confounding was controlled for with a large number of confounders (more than two) and/or unobserved confounding was also controlled for.

Control of the population

Perhaps the main relevant variable that should not be omitted by any study is that of population at risk, either in the study area (in ecological studies) or in the area in which the subject resides (in individual studies). It is evident that both incidence and mortality, as well as other outcomes (hospitalizations, ICU admissions, etc.), depend both on the population of the area under study and on the age structure of that population.

Population control can be carried out in various ways: using rates, including the population or the expected value of the outcome in each area under study in the model as an offset, or controlling, as covariates, the size of the population or its structure (for example, percentage of population aged 65 years or more).

A control of the population can also be achieved by including population density (i.e., the number of people per unit of area, usually per square kilometre) as a covariate. However, it is possible that, in this case, control would only be partial. On one hand, an area with a higher population density does not always have more population than another, but it depends, logically, on its surface. On the other hand, population density could be capturing other socioeconomic variables.

This domain was scored with a 3 if the population was not controlled for by any method, a 2 if the population was controlled for by only including population density as a covariate, or a 1 if the population was controlled for, in addition to including the population density by other additional method.

Control of the spatial and/or of the temporal dependence

Several studies analyze, as outcome, cumulative cases and cumulative deaths. Many others, however, use a temporal design. This is a design, where both the outcome and its possible explanatory variables, as well as the covariates, are measured in the form of time series. Time series are observed with a certain periodicity, usually regular (for example, daily) over a given period of time.

In this case there is temporal dependency. The outcome observations are not independent but are related, so their future behavior is predictable. In general, this dependence can be long or short term. A long-term dependency, or trend, could be defined as a movement or tendency in the data. As is known, in the case of COVID-19 there have been between two and four waves, depending on the country. That is, long-term swings have occurred. Periods in which the outcome values are persistently high, followed by others in which the values have been low. Short-term dependency, also called serial autocorrelation, refers to the relationship of the values of an outcome on, for example, a given day with the values of the previous days, especially with those of the preceding day.

Most studies use a spatial or spatio-temporal design. In other words, they observe the outcome in different geographical areas, and sometimes over time. When a spatial design is available, it is important to distinguish two sources of variation. In the first place, the most important source is usually the so-called 'spatial dependence' and is a consequence of the correlation of the spatial unit with neighboring spatial units, generally those that are geographically contiguous. In this way, the risks (for example, of transmission) of contiguous or nearby areas are more similar than the risks of spatially distant areas. Part of this dependency is not really a structural dependency but is mainly due to the existence of uncontrolled variables, that is, not included in the analysis. Meanwhile, the second source, the existence of spatially independent and unrelated variation called ‘spatial heterogeneity’, must be assumed. This is a consequence of the existence of unobserved variables without spatial structure that could influence risk [ 14 ].

The temporal and the spatial dependence must be controlled for, because, otherwise, in the best of cases, the variances of the estimators will be misleading (when the outcome is a continuous variable, normally distributed, and least squares methods are used for the inference) and in most cases, not only will the variances be biased, but the estimators will also be biased (when the outcome is not a continuous variable, not normally distributed, and least squares methods cannot be used) [ 12 ].

In some studies, the control of temporal or spatial dependence is not applicable. Thus, in studies with a time series design but in which a very short period of time is analyzed, it does not make sense to control for temporal dependence. Likewise, in those studies with a spatial (or spatio-temporal) design but that analyze very spatially distant territories (for example, several countries in the world) it does not make sense to control for the spatial dependence.

We scored this domain with a 3 when neither temporal nor spatial dependency was controlled and should have been; a 2 when the control was partial, controlling only one dependency and not controlling the other; and a 1 when they were controlled.

Control of non-linearities

Along with the omission of relevant variables, the error in the functional form constitutes the most important specification error. The relationships between environmental variables and COVID-19 outcomes are not usually linear. Thus, for example, in Fig.  2 , we show the smoothed curves for the relationship between the daily temperature and the daily levels of nitrogen dioxide (NO 2 ) and the daily number of cases for Spain in the period between January 1, 2020 and April 14, 2021. Specifically, we draw the estimated curves in a generalized additive model in which we use smoothing splines with a quasi-likelihood Poisson link, i.e., taking into account over-dispersion.

. Environmental data [ 81 , 82 ]

Smoothed curves for the relationships between daily temperature and daily levels of nitrogen dioxide and the number of daily cases of COVID-19. Spain, January 1, 2020 to April 14, 2021. The data were obtained from: [ 16 ]

As can be seen, in none of the cases was the relationship linear. These non-linearities must be controlled in the models, because, otherwise, as when relevant variables are omitted, the estimators will be inconsistent and their variances misleading.

We scored this dimension with a 3 if non-linearities were not controlled for (again, when applicable) or a 1 if they had been controlled.

Measurement errors

Measurement errors (also known as misclassification) can occur in both the response variable and in the exposure variables.

The definition of the response variable can vary in space and time, even within the same country, leading to differential misclassification. In Spain, for example, the Catalan government, on the one hand, defined a death from COVID-19 as being a positive result on some test (PCR or fast test) or symptoms presented at some point which a health professional subsequently classified as a possible case, but the individual did not have a diagnostic test with a positive result [ 15 ], whereas on the other hand, the Spanish government, defined a death from COVID-19 as being someone who presented a positive PCR result [ 16 ], thus providing significantly lower figures. This misclassification continued until May 21, 2020, when the Government of Spain adopted the same definition as the Government of Catalonia [ 17 ].

However, the measurement errors in the response variable are not attributable to the investigators, although they should certainly discuss them if appropriate. Furthermore, fortunately, when measurement errors occur in the dependent variable, the estimators remain consistent, although they are not efficient [ 12 ], that is, not very precise, thus leading to wider confidence intervals than if there had been no measurement errors.

There is, however, an important problem if measurement errors occur in the explanatory variables (exposure or covariates). If the explanatory variables are measured with error, the estimators will be inconsistent [ 12 ].

Even in studies at the individual level, the exposure variables and, obviously, the contextual variables (for example, the socioeconomic ones) are not observed at the individual level, but are aggregated at the level of the area under study. Nevertheless, not all residents in the area under study are actually exposed to the same mean values of the explanatory variables, which leads to a measurement error. If the misclassification is non-differential (over time and over space within the area under study) and, furthermore, if the between-area variability of the variable measured with error is much greater than the within-area variability of such variable, that is, that the area under study is not very heterogeneous (for example, because it is a small area), then the effect of the measurement error on the estimator consistency may be negligible [ 18 ]. This is what happens in the case of contextual socioeconomic variables as long as the area under study is not very large.

In the exposure variables (both air pollutants and meteorological variables), however, there is differential misclassification, because the exposure exhibits spatial variation across the area under study. If the spatial structure (i.e., spatial dependence) of the data is ignored, the estimators will be biased and inconsistent [ 19 ]. Many studies use the measurements observed in the area under study to estimate, by means of point estimators, exposure levels for that entire area. The estimators most widely used are the arithmetic mean of the values of the exposure, observed in several monitoring or meteorological stations in the area, and sometimes the inverse-distance weighted average of these values.

This measurement error in the exposure variables must be controlled for, either explicitly incorporating the spatial dependence, in the ecological studies, or by correcting the misalignment between the locations of the observation points of the exposure variables and that locations of the individuals, in the studies at the individual level.

In studies with an ecological spatial design, the 'modifiable areal unit problem' (MAUP) occurs [ 20 ]. The MAUP is a consequence either because areas of different sizes are added (scale effect) and/or because of the way the area is divided (zoning effect) [ 21 ]. In either case, it is a potential source of bias. For example, Wang and Di found that the association between nitrogen dioxide (NO 2 ) and COVID-19 deaths varies when the data is aggregated at different levels: a risk factor when the area is smaller (aggregation of districts and cities) and a protective factor at the province level [ 22 ]. Similarly, we also found a positive association between NO 2 and deaths as a consequence of COVID-19 at the level of a county-like area [ 17 ] and no association at a lower level of aggregation [ 23 ].

When using a temporal design, the ‘modifiable temporal unit problem’ (MTUP) [ 24 ] also occurs, whereby the results depend on the way data are temporally aggregated [ 21 ]. Furthermore, in this type of design, temporal misalignment can occur. In other words, the relationship between exposure and the occurrence of COVID-19 outcome is not contemporary, but rather is distributed over time as a consequence of the incubation period of COVID-19 and due to the diagnostic delays of the outcome. This temporal misalignment must be controlled by including lags, for example.

We scored this dimension with a 3 if measurement errors in the exposure variables are not controlled at all, a 2 if they are only partially controlled (not including lags, for example) or the areas under study are very large (countries, for example) and a 1 if they have been controlled for.

Statistical model

Many of the studies, even though the response variable is a count data, used regression models with normally distributed errors (linear regression models, generalized linear and additive models with Gaussian link, etc.). Using this type of models leads to biased results, unless the number of counts is very large. However, this was not the case in most studies.

Some studies did not model the counts but rather the rates, dividing the dependent variable by the size of the population. However, since the numerator, being a count data, is actually distributed following a Poisson distribution, the variance is proportional to the mean, so it is not constant, leading to heteroscedasticity (i.e., overdispersion). This must be controlled for, otherwise, the variances of the estimators are misleading.

To illustrate the effects on the results of erroneously using a regression model with normally distributed errors, we used the data in Filippini et al. [ 25 ]. Their objective was to investigate the link between the transmission of SARS-CoV-2 infection and long-term exposure to NO 2 in the provinces of three regions of Northern Italy (Lombardia, Venetto and Emilia Romagna), between March 8 and April 5, 2020 ( n  = 84). Using their data, we first estimated a linear regression model including, as a dependent variable, the number of new daily SARS-CoV-2 positive cases (count data variable). We found that long-term NO 2 levels to which the inhabitants of the provinces of the Italian regions studied had been exposed to be positively associated with the total number of cases that occurred in the period considered. Specifically, for every 1 μg/m 3 increase in the NO 2 levels, the number of cases increased by 18.478 for the entire period (95% confidence interval, 95% CI 10.285–27.210). However, the residuals of the model were not normally distributed (Fig.  3 ). We then modelled the rates (cases per 100,000 inhabitants) using a linear regression model, although we did not control for heteroscedasticity. For every 1 μg/m 3 increase in NO 2 , the number of cases increased by 1.207 cases per 100,000 inhabitants (95% CI 0.050–2.364). However, the residuals presented a clear heteroscedasticity behavior (the scatter plot of the residuals against the adjusted values did not present a constant dispersion, i.e., variance), and furthermore, they were not normally distributed (Fig.  3 ). When we estimated a generalized Poisson model, in which we took into account the over-dispersion, and in which we included the population size as an offset, we could not reject the null hypothesis that the parameter associated with the long-term exposure of NO 2 was equal to zero (95% CI: − 0.004, 0.001).

Residual analysis of the linear regression models relating the transmission of SARS-CoV-2 infection and long-term exposure to NO 2 in the provinces of three regions of Northern Italy (Lombardia, Venetto and Emilia Romagna), between March 8 and April 5, 2020. a Response variable: new daily SARS-CoV-2 positive cases. b Response variable: new daily SARS-CoV-2 positive cases per 100,000 habs. The data were obtained from: [ 25 ]

We scored this dimension with a 3 when the outcome was a count data and regression models with normally distributed error were used. We also scored a 3 when rates were modelled but heteroscedasticity was not controlled for. Meanwhile, we scored a 2 if rates were modelled and heteroscedasticity was controlled, and a 1 if models for count data response variables were used (Poisson regression, negative binomial regression, etc.).

Figure  1 shows a flowchart of the review process. Of the 5631 abstracts initially identified, and after excluding duplicates, we were left with 3238 studies. From these we excluded 3063 studies that did not refer to SARS-CoV-2 or COVID-19, preprints, comments, those purely narrative studies, editorials and reviews and systematic reviews, thus leaving us with 175 eligible studies. As we said, we excluded 43 studies that were purely descriptive and those that did not include any type of regression model (Additional file 1 : Table S1). In the end we were left with 132 studies with which to carry out the qualitative synthesis (Additional file 1 : Tables S2 and S3).

Of the 132 studies, 92 referred to meteorological variables, 40 to socioeconomic variables and 34 to air pollutants. Seventy-one of the studies referred only to meteorological variables, 21 only to socioeconomic variables and 16 only to air pollutants. Of the 92 studies that referred to meteorological variables, 16 also considered air pollutants, 14 meteorological variables and socioeconomic variables. Four of the studies referring to air pollutants also referred to socioeconomic variables but not to meteorological variables. Nine referred to meteorological variables and socioeconomic variables but not to air pollutants. Finally, five studies considered meteorological variables, air pollutants and socioeconomic variables (Additional file 1 : Figure S1).

Of the 132 studies finally selected, 124 used an ecological design and nine an individual design. Most ecological studies considered different regions (states, regions, provinces, counties, cities, etc.) within the same country as study populations (71 studies). This is followed by those that considered countries or cities in the world (34 studies) and, finally, those that considered individual cities or smaller areas (19 studies). Seven of the eight studies with an individual design, analyzed the influence of socioeconomic variables, while only two considered socioeconomic variables and air pollutants.

Most of the studies (129 out of 132) analyzed data referring up to August 1, 2020 (i.e., only considering the first wave). In fact, only three consider the first two waves of the pandemic.

Table 2 shows the evaluation of the studies included in the qualitative synthesis. Of the 132 eligible studies, we evaluated 63.64% (84 of 132) as weak (high risk of bias), 19.70% (26 of 132) as moderate (moderate risk of bias) and 16.67% (22 of 132) as strong (low risk of bias). Only four studies did not have any dimension scored with a 3 (high risk of bias) [ 17 , 26 , 27 , 28 ].

In decreasing order of the studies that considered socioeconomic variables, 62.50% (25 of 40 studies) were evaluated as moderate (15 studies, 37.50%) or strong (10, 25.00%). Of the 34 which considered air pollutants, 41.18% (14 studies) were evaluated as moderate (9 studies, 26.47%) or strong (5 studies, 14.71%). Finally, of the 92 studies that considered meteorological variables, 25.00% (23 studies) were evaluated as moderate (11 studies, 11.96%) or strong (12 studies, 13.04%).

However, in the case of studies that consider socioeconomic variables, it should be noted that the high risk of bias could be underestimated. As is known, socioeconomic variables are contextual variables measured at an ecological level in a geographic area and invariant over time. Their influence on COVID-19, if any, is highly unlikely to be non-linear. Consequently, in many cases this dimension was not evaluated.

The dimension in which we evaluated more studies with a high risk of bias was that of measurement errors (90 of 132 studies, 68.19%), followed by the control of the spatial and temporal dependence dimension (80 studies, 60.61%) and of the statistical model (77 studies, 58.33%) and control of non-linearities (73 studies, 55.30%) dimensions. The dimensions with fewer studies with a high risk of bias were confounding bias (47 studies, 35.61%) and control of the population (53 studies, 40.15%).

Findings from studies assessed as moderate or strong

In relation to the studies that considered meteorological variables, the ones that we evaluated as moderate or strong [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ] have not consistently found an attenuating effect of meteorological variables. That is, they have not found that high temperature and low humidity were associated with lower incidence or mortality from COVID-19. In seven of 22 studies, temperature was either positively associated or not statistically associated with incidence [ 27 , 30 , 34 , 35 , 44 ], transmission (reproductive number) [ 46 ] and mortality [ 28 ] (four out of 11 studies were assessed as strong and another three out of 11 studies assessed as moderate). Among the studies that found an attenuating effect, five (three evaluated as strong [ 31 , 38 , 40 ] and one as moderate [ 41 ]) did not include lags and, therefore, assumed that the effect of the meteorological variables was contemporaneous. The studies that did include lags were evaluated with high risk of bias in some dimension. In particular, control of non-linearities [ 32 , 39 , 42 , 45 , 48 ], confounding bias [ 37 , 43 , 48 ], and measurement errors [ 37 , 42 , 47 ], followed by control of population [ 29 , 36 ] and control of spatial and/or temporal dependence [ 33 , 39 ]. Interestingly, Xie et al. [ 27 ], whose units of analysis were 122 Chinese cities, (a study that we evaluated as strong and did not have any dimension evaluated as high risk), points out that there is no evidence supporting that case counts of COVID-19 could decline when the weather becomes warmer.

There was very little evidence in relation to other meteorological variables such as wind speed (only two strong [ 33 , 49 ] and one moderate [ 34 ] study analyzed it and found a negative association between wind speed and incidence); cloud percentage [ 29 ] or solar radiation [ 42 ] (both evaluated as moderate and with contradictory results: higher percentage of cloud was associated with higher incidence, while no association was found with solar radiation); or precipitation (considered in only one strong study that found a significant negative association with incidence [ 31 ]).

Greater consistency was found in the association between greater exposure to levels of air pollution, especially long-term exposure, and an increase in COVID-19 outcomes, both in ecological [ 17 , 28 , 29 , 44 , 48 , 49 , 50 , 51 , 54 , 55 , 56 ] and individual studies [ 52 , 53 ]. The areas that were most exposed to air pollution were those with the highest incidence (new daily cases, new positive tests, and cumulative cases) [ 17 , 29 , 44 , 48 , 49 , 53 , 54 ] and the highest mortality [ 17 , 28 , 29 , 49 , 50 , 51 , 52 , 55 , 56 ] from COVID-19. This result occurs, above all, for fine particles, PM 2.5 [ 28 , 44 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ], but also for ozone, O 3 [ 29 , 49 , 50 ], coarse particles, PM 10 [ 17 , 50 ], nitrogen dioxide, NO 2 [ 17 , 50 ], benzene [ 55 ] and for an air quality index [ 48 ]. In Saez et al. [ 17 ] (which we evaluated as strong) as in Adhikari et al. [ 29 ] and Rodríguez-Villamizar et al. [ 56 ] (these last two evaluated as moderate), some of the pollutants were not found to be associated with mortality (PM 10 in Saez et al., O 3 in Adhikari et al., PM 2.5 in Rodríguez-Villamizar et al.).

In relation to studies that considered socioeconomic variables, as we said, we must distinguish between the findings of ecological [ 17 , 28 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ] and individual studies [ 53 , 67 , 68 , 69 , 70 , 71 , 72 ]. In the ecological studies, there was no consistent association between socioeconomic contextual variables and COVID-19 outcomes. In just over half of the studies, the socioeconomic variables were risk factors and in the rest they were either protective factors or no statistically significant association was found. Even in some studies, such as Saez et al. [ 17 ] or Wu X et al. [ 28 ] (both of which we evaluated as strong and did not have any dimension evaluated with high risk of bias), apparently contradictory results were found. Thus, in Saez et al. [ 17 ], whose unit of analysis were small areas (counties and health zones, some made up of census tracts, others by municipalities) in Catalonia, Spain, the higher the percentage of poor housing in the small area and the more economically deprived the area was, the greater the risk of a positive result and death. Conversely, the higher the unemployment rate and the percentage of foreigners in the small area, the lower the risk of a positive result and death. In Wu et al. [ 28 ], whose units of analysis were US counties, while percent of the adult population with less than high school education and percent of Black residents, both in the county, were found to be positively associated with the number of deaths in the county, the median household income, the percentage of owner-occupied housing and, marginally, the median house value were also found positively associated. Meanwhile, others, such as the percentage of people in the county in poverty, were not found to be statistically significant associated.

More consistency has been found in relation to population density. In the areas with a higher population density, there was a higher incidence, a higher number of positives, a higher transmission (measured by the reproductive number) and a higher number of deaths than in others less densely populated areas. In Wu et al. [ 28 ], however, the higher the population density, the lower the risk of mortality (although statistical significance only occurs in the fourth quintile).

Of the seven individual studies that we evaluated as moderate or strong, five found an association between both individual socioeconomic status (income, non-white ethnicity—especially Blacks-, lower educational attainment, being an immigrant from a low- or middle-income country) and contextual (income of the area, where the subject resided, residing in a neighborhood with financial insecurity) and various COVID-19 outcomes (positive tests, hospital admissions and deaths). We did, however, find one exception. In Price-Haywood et al. (a study that we evaluated as strong), whose study population was the Ochsner Health facility in New Orleans, Louisiana, USA, Black race was not associated with higher in-hospital mortality than white race, after adjustment for differences in sociodemographic and clinical characteristics on admission [ 70 ].

Our results, both with regard to the methodological limitations that we found in the review and the results of the studies that control them, were similar to those of other reviews. Regarding the methodological limitations, we will refer, in order of publication, to two reviews (not systematic): one that considered air pollutants [ 73 ] and the other meteorological variables [ 74 ]. Villeneuve and Goldberg review six studies on COVID-19 (only two were peer-reviewed) and two on SARS, published up to May 2020 [ 74 ]. Hunter Kerr et al. review 43 studies (23 of them peer-reviewed), published in 2020 [ 74 ]. Both reviews found, as we did, that all studies have methodological limitations in one way or another. Almost all the methodological limitations that we have pointed out here were also considered in these two reviews. There are, however, some differences. Hunter Kerr et al. did not consider choosing a statistical model with normally distributed errors [ 74 ] as a limitation. Villeneuve and Goldberg, for their part, did not consider the error of the functional form (i.e., control of non-linearities), at least directly, inasmuch as they do so indirectly by pointing out, as a limitation, the inadequate evaluation of effect modification [ 73 ]. In contrast, Villeneuve and Goldberg point out, as the most important error, possible cross-level bias in ecological studies.

Regarding the influence of environmental variables (meteorological and air pollutants) in COVID-19 outcomes, the findings of the studies evaluated as moderate or strong in our review, coincided with the findings of the other reviews (both systematic and non-systematic).

We cannot conclude that there was an attenuating effect of weather conditions on the spread of the COVID-19 pandemic. In addition to the fact that, as mentioned, we did not find a systematic behaviour in the reviewed studies, so the attenuation shown by some of them could actually be a consequence of an inadequate adjustment. Thus, on the one hand, the study period of all the studies reviewed by the systematic reviews of Mecenas et al. [ 2 ], Smit et al. [ 3 ] and McClymont and Hu [ 4 ] as well as by the Hunter Kerr et al.’s review [ 74 ], corresponded to the first wave. The same occurs with most of the studies in our review (all except three). However, with a single exception [ 45 ], none of the studies controlled for non-pharmaceutical interventions either as containment or suppression strategies undertaken in that period. Thus, in this case, the reduction in the spread of the pandemic as temperature increased and humidity decreased, could have been confounded by the effects of lockdowns and other restrictions. Although Tobías and Molina [ 45 ] controlled for the effects of lockdown (and also those of seasonality as a consequence of weekends), they did not adjust for other confounders. Consequently, and perhaps for this reason, they found a significant effect only in the contemporary association (the same day) between an increase in temperature and a reduction in the incidence rate. We believe that, if they exist, the effect of meteorological variables on the spread of COVID-19 would be indirect. In the spring–summer of 2020, better weather conditions (higher temperature, lower relative humidity, lower wind speed, etc.) and a relaxation of restrictions, led to greater mobility and, therefore, greater social contact that, in turn, led to an increase in transmission and, consequently, in incidence. This was what happened, for example, in Spain during the second wave (which began in August 2020) [ 23 ].

The results of all reviews, including ours, suggest that there is an association between exposure to air pollutants (particularly in the long term but also in the short term) and COVID-19 outcomes. In fact, two hypotheses have been suggested that would explain this association. First, some studies have proposed that air particulate matter can operate as a virus carrier, promoting the spread of the SARS-CoV-2 [ 74 , 75 , 76 ]. It should be noted, however, that these studies were either not eligible as they used only correlation analysis to test their hypothesis [ 75 ] or they were eligible but were assessed as a high risk of bias [ 76 ].

A second hypothesis has been proposed which suggests there could be potential biological mechanisms that may explain the association between air pollutants and respiratory viral infections. According to this, the effects of exposure to air pollutants would occur not so much on transmission or incidence but on the worsening of the disease (hospitalization, ICU admissions, mortality). Exposure exacerbates the severity of COVID-19 infection symptoms and worsens the prognosis of COVID-19 patients [ 73 ]. In this sense, Wu X et al. [ 28 ] argue that long-term exposure to PM 2.5 could cause alveolar angiotensin-converting enzyme 2 (ACE-2) receptor overexpression and impairs host defences [ 77 ]. This could cause a more severe form of COVID-19 in ACE-2—depleted lungs, increasing the likelihood of poor outcomes, including death [ 78 ]. We, however, believe that air pollutants have actually been surrogates of other variables, such as the mobility of residents and several socioeconomic conditions (high population density, poor housing, use of public transport, occupations in which it is not possible to telecommute, etc.) that facilitate social contact [ 17 ]. In fact, Dey and Dominici, in a very recent editorial commenting on the study by Wu et al. [ 28 ], and of which Dominici is a co-author, point out that the health risks of some racial subgroups are spiraling as they have higher levels of exposure to air pollutants, hence being more susceptible to mortality from COVID-19 [ 79 ]. We do not deny that exposure to air pollutants had an independent effect on, above all, the worsening of the disease among those diagnosed with COVID-19. However, we are convinced that this effect cannot be observed using an ecological design.

As we noted, we have found a consistency in the effects of socioeconomic variables on COVID-19 outcomes only in individual studies and in indicators also at the individual level (ethnicity—particularly being Black—education, etc.). We believe that the effect, if it exists, would be indirect. Poorer socioeconomic conditions would be associated, on the one hand, with greater social contact, which would affect the transmission of the virus and the incidence of COVID-19 and, on the other, with a greater number of comorbidities and greater difficulties in accessing health care which would affect a poorer prognosis of the disease. Furthermore, poorer socio-economic conditions could be related both to a differential exposure to air pollution and to a differential susceptibility to its effects (i.e., modification of the effect) [ 80 ].

In short, a large part of the methodological problems that we have encountered and, therefore, of the uncertainty in the findings, are the consequence of using an ecological design. In this sense, we could not agree more with Hunter Kerr et al. [ 74 ], who recommend, as an epidemiological design, a longitudinal study with individual-level data, in which those diagnosed with COVID-19 would be followed through time.

Our study may have three limitations. First, some studies published during 2020 may have escaped us. That said, this is unlikely, since, as of January 2021, we have been regularly reviewing PubMed and periodically reviewing the other databases. Nevertheless, it is not impossible that a study may have eluded us. Second, both the information extraction and the quality control we carried out could have some subjectivity. We have tried to minimize this as much as possible.

Finally, as we noted, the rating of both the domains and the studies are based on Parmar et al. [ 8 ], with the only difference being that in Parmar et al., an overall rating of strong was given if none of its domains was rated as weak. In our case, this assignment seemed too restrictive. In fact, applying this criterion would imply that only one of the studies could be rated as strong. In our case, we observed some biases that were not contemplated in Parmar et al., such as the lack of control of the population and of the spatial and/or temporal dependence, the non-control of non-linearity and the inappropriate use of statistical models. In our case, the probability that at least one of these biases occurred was very high. In any case, we admit that there could be some degree of arbitrariness in the assignment of the overall rating to one category or another.

All the studies we reviewed have methodological limitations to a greater or lesser extent. Even those that we have evaluated as strong (16.67% of the studies reviewed) and, among them, those in which we did not evaluate any dimension as having a high risk of bias (4 studies), have the limitation of using an ecological epidemiological design or, in any case, either of measuring the exposure in an ecological way (exposure misclassification). These limitations prevent conclusions about the effects of environmental (meteorological and air pollutants) and socioeconomic variables on COVID-19 outcomes being drawn. However, we dare to argue that the effects of these variables, if they exist, would be indirect, based on their relationship with social contact. In any case, the estimation of these independent effects requires the use of an individual design and the control of the methodological limitations explained in this work. Among them, an estimate of individual exposure free of biases (non-differential misclassification, non-existence of spatial–temporal misalignment, etc.).

Availability of data and materials

All the studies, as well as the code to make the figures, can be requested from the corresponding author ([email protected]).

Abbreviations

Novel coronavirus disease

Fine particles with a diameter of 2.5 microns (μm) or less

Nitrogen dioxide

Coarse particles with a diameter of 10 μm or less

Severe acute respiratory syndrome coronavirus 2

Particulate matter

Prospective Register of Systematic Reviews

Preferred reporting items for systematic reviews and meta-analysis

Item Bank for Assessment of Risk of Bias and Precision for Observational Studies of Interventions or Exposures

Polymerase chain reaction

Modifiable areal unit problem

Modifiable temporal unit problem

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Acknowledgements

This study was carried out within the ‘Cohort-Real World Data’ subprogram of CIBER of Epidemiology and Public Health (CIBERESP).

This work was partially financed by the SUPERA COVID19 Fund from SAUN: Santander Universidades, CRUE and CSIC, and by the COVID-19 Competitive Grant Program from Pfizer Global Medical Grants. The funding sources did not participate in the design or conduct of the study, the collection, management, analysis, or interpretation of the data, or the preparation, review, or approval of the manuscript.

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MS had the original idea for the paper. MS designed the study. The bibliographic search and the writing of the introduction were carried out by MS and MAB. The methods were chosen and performed by all authors. MAB created the tables and figures. All authors wrote the results and the discussion. The writing and final editing was done by all authors. All authors reviewed and approved the manuscript.

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Additional file 1: table s1.

. List of studies excluded. Table S2 . Studies included in the qualitative synthesis Table S3 . List of studies included in the qualitative synthesis. Figure S1. Number of studies by type of explanatory variable analyzed

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Barceló, M.A., Saez, M. Methodological limitations in studies assessing the effects of environmental and socioeconomic variables on the spread of COVID-19: a systematic review. Environ Sci Eur 33 , 108 (2021). https://doi.org/10.1186/s12302-021-00550-7

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The Potential Impact of COVID-19 on Health-Related Quality of Life in Children and Adolescents: A Systematic Review

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This was a systematic review of studies examining the effect of COVID-19 on the health-related quality of life (HRQoL) of children and adolescents. The review was conducted by examining the current literature and analyzing up-to-date evidence. The studies were extracted from three major databases (CINAHL Complete, MEDLINE, and Web of Science) and analyzed. Studies on children and adolescents whose HRQoL has been affected by COVID-19 were included based on the eligibility criteria. Ultimately, eight studies met these criteria. The evidence of the selected studies was analyzed; the research design, age categories, respondents, evaluation tools, gender differences, and variability before and during COVID-19 were systematically reviewed. This review found differences in these groups regarding oral symptoms, functional limitations, emotional well-being, and social well-being. Furthermore, this review highlighted the relative paucity of studies that comprehensively investigate the latest evidence of changes in the HRQoL of children and adolescents due to COVID-19 in preparation for the post-COVID era.

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Challenges and burden of the Coronavirus 2019 (COVID-19) pandemic for child and adolescent mental health: a narrative review to highlight clinical and research needs in the acute phase and the long return to normality

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• Copy URL https://www.pbs.org/newshour/health/scientists-are-piecing-together-the-puzzle-of-long-covid-heres-what-to-know

Scientists are piecing together the puzzle of long COVID. Here’s what to know

Since 2020, the condition known as long COVID-19 has become a widespread disability affecting the health and quality of life of millions of people across the globe and costing economies billions of dollars in reduced productivity of employees and an overall drop in the work force .

The intense scientific effort that long COVID sparked has resulted in more than 24,000 scientific publications , making it the most researched health condition in any four years of recorded human history.

Long COVID is a term that describes the constellation of long-term health effects caused by infection with the SARS-CoV-2 virus. These range from persistent respiratory symptoms, such as shortness of breath, to debilitating fatigue or brain fog that limits people’s ability to work, and conditions such as heart failure and diabetes, which are known to last a lifetime.

READ MORE: New long COVID guidance aims to help doctors identify mental health symptoms

I am a physician scientist, and I have been deeply immersed in studying long COVID since the early days of the pandemic. I have testified before the U.S. Senate as an expert witness on long COVID , have published extensively on it and was named as one of Time’s 100 most influential people in health in 2024 for my research in this area.

Over the first half of 2024, a flurry of reports and scientific papers on long COVID added clarity to this complex condition. These include, in particular, insights into how COVID-19 can still wreak havoc in many organs years after the initial viral infection, as well as emerging evidence on viral persistence and immune dysfunction that last for months or years after initial infection.

Early on in the pandemic, the SARS-CoV-2 virus seemed to be primarily wreaking havoc on the lungs. But researchers quickly realized that it was affecting many organs in the body. Photo by Benoit Tessier via Reuters.

How long COVID affects the body

A new study that my colleagues and I published in the New England Journal of Medicine on July 17, 2024, shows that the risk of long COVID declined over the course of the pandemic. In 2020, when the ancestral strain of SARS-CoV-2 was dominant and vaccines were not available, about 10.4 percent of adults who got COVID-19 developed long COVID. By early 2022, when the omicron family of variants predominated, that rate declined to 7.7 percent among unvaccinated adults and 3.5 percent of vaccinated adults. In other words, unvaccinated people were more than twice as likely to develop long COVID.

READ MORE: Years into the pandemic, scientists are still trying to understand long COVID

While researchers like me do not yet have concrete numbers for the current rate in mid-2024 due to the time it takes for long COVID cases to be reflected in the data, the flow of new patients into long COVID clinics has been on par with 2022.

We found that the decline was the result of two key drivers: availability of vaccines and changes in the characteristics of the virus – which made the virus less prone to cause severe acute infections and may have reduced its ability to persist in the human body long enough to cause chronic disease.

Despite the decline in risk of developing long COVID, even a 3.5 percent risk is substantial. New and repeat COVID-19 infections translate into millions of new long COVID cases that add to an already staggering number of people suffering from this condition.

Estimates for the first year of the pandemic suggests that at least 65 million people globally have had long COVID. Along with a group of other leading scientists, my team will soon publish updated estimates of the global burden of long COVID and its impact on the global economy through 2023.

In addition, a major new report by the National Academies of Sciences Engineering and Medicine details all the health effects that constitute long COVID . The report was commissioned by the Social Security Administration to understand the implications of long COVID on its disability benefits.

It concludes that long COVID is a complex chronic condition that can result in more than 200 health effects across multiple body systems. These include new onset or worsening:

• heart disease
• neurologic problems such as cognitive impairment , strokes and dysautonomia . This is a category of disorders that affect the body’s autonomic nervous system – nerves that regulate most of the body’s vital mechanisms such as blood pressure, heart rate and temperature.
• post-exertional malaise , a state of severe exhaustion that may happen after even minor activity — often leaving the patient unable to function for hours, days or weeks
• gastrointestinal disorders
• kidney disease
• metabolic disorders such as diabetes and hyperlipidemia , or a rise in bad cholesterol
• immune dysfunction

Long COVID can affect people across the lifespan from children to older adults and across race and ethnicity and baseline health status. Importantly, more than 90 percent of people with long COVID had mild COVID-19 infections.

The National Academies report also concluded that long COVID can result in the inability to return to work or school; poor quality of life; diminished ability to perform activities of daily living; and decreased physical and cognitive function for months or years after the initial infection.

READ MORE: These 12 symptoms may define long COVID, new study finds

A long road ahead

What’s more, health problems resulting from COVID-19 can last years after the initial infection.

A large study published in early 2024 showed that even people who had a mild SARS-CoV-2 infection still experienced new health problems related to COVID-19 in the third year after the initial infection.

Such findings parallel other research showing that the virus persists in various organ systems for months or years after COVID-19 infection. And research is showing that immune responses to the infection are still evident two to three years after a mild infection. Together, these studies may explain why a SARS-CoV-2 infection years ago could still cause new health problems long after the initial infection.

WATCH: People living with long COVID explain how the disease changed their lives

Important progress is also being made in understanding the pathways by which long COVID wreaks havoc on the body. Two preliminary studies from the U.S. and the Netherlands show that when researchers transfer auto-antibodies – antibodies generated by a person’s immune system that are directed at their own tissues and organs – from people with long COVID into healthy mice, the animals start to experience long COVID-like symptoms such as muscle weakness and poor balance.

These studies suggest that an abnormal immune response thought to be responsible for the generation of these auto-antibodies may underlie long COVID and that removing these auto-antibodies may hold promise as potential treatments.

An ongoing threat

Despite overwhelming evidence of the wide-ranging risks of COVID-19, a great deal of messaging suggests that it is no longer a threat to the public. Although there is no empirical evidence to back this up, this misinformation has permeated the public narrative.

The data, however, tells a different story.

This article is republished from The Conversation under a Creative Commons license. Read the original article .

Ziyad Al-Aly is chief of research and development at VA St. Louis Health Care System and a clinical epidemiologist at Washington University.

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• Majority in U.S. Says Public Health Benefits of COVID-19 Restrictions Worth the Costs, Even as Large Shares Also See Downsides

73% say they are vaccinated, but at least half express confusion, concern over vaccine information and health impacts

Table of contents.

• Acknowledgments
• Methodology
• Appendix: Detailed charts and tables

Pew Research Center conducted this study to understand how Americans are continuing to respond to the coronavirus outbreak. For this analysis, we surveyed 10,348 U.S. adults from Aug. 23 to 29, 2021.

Everyone who took part in the survey is a member of the Center’s American Trends Panel (ATP), an online survey panel that is recruited through national, random sampling of residential addresses. This way, nearly all U.S. adults have a chance of selection. The survey is weighted to be representative of the U.S. adult population by gender, race, ethnicity, partisan affiliation, education and other categories. Read more about the ATP’s methodology .

See here to read more about the questions used for this report, along with responses and its methodology .

More than a year and a half into the coronavirus outbreak, large shares of Americans continue to see the coronavirus as a major threat to public health and the U.S. economy. And despite widespread vaccination efforts, 54% of U.S. adults say the worst of the outbreak is still to come.

The toll of restrictions on public activities in order to slow the spread of the coronavirus is deeply felt across groups: Overwhelming majorities say restrictions have done a lot or some to hurt businesses and economic activity and keep people from living their lives the way they want. Smaller majorities say these restrictions have helped at least some to prevent hospitalizations and deaths from the coronavirus and to slow the spread of the virus. Still, when asked to issue an overall judgment, Americans on balance view the public health benefits of these restrictions as having been worth the costs (62% to 37%).

A new national survey by Pew Research Center, conducted from Aug. 23 to 29 among 10,348 U.S. adults, prior to President Joe Biden’s announcement of COVID-19 vaccine mandates for employers, finds that 73% of those ages 18 and older say they’ve received at least one dose of a vaccine for COVID-19, with the vast majority of this group saying they have received all the shots they need to be fully vaccinated. About a quarter of adults (26%) say they have not received a vaccine.

Vaccination rates vary significantly across demographic groups, with smaller majorities of younger adults, those with lower family incomes and those living in rural areas saying they’ve received a COVID-19 vaccine. No more than six-in-ten of those without health insurance and White evangelical Protestants say they’ve been vaccinated (57% each). Notably, Black adults are now about as likely as White adults to say they’ve received a vaccine. Earlier in the outbreak, Black adults were less likely than White adults to say they planned to get a COVID-19 vaccine.

Partisan affiliation remains one of the widest differences in vaccination status: 86% of Democrats and independents who lean toward the Democratic Party have received at least one dose of a COVID-19 vaccine, compared with 60% of Republicans and Republican leaners.

Americans express a range of sometimes cross-pressured sentiments toward vaccines. Overall, 73% say the statement “vaccines are the best way to protect Americans from COVID-19” describes their views very or somewhat well; 60% say their views are described at least somewhat well by the statement “people who choose not to get a COVID-19 vaccine are hurting the country.”

At the same time, 51% of the public says that the phrase “there’s too much pressure on Americans to get a COVID-19 vaccine” describes their own views very or somewhat well. And 61% say the same about the statement “we don’t really know yet if there are serious health risks from COVID-19 vaccines.”

Vaccinated adults and those who have not received a vaccine differ widely in their views of vaccines – as well as other elements of the broader coronavirus outbreak. For instance, 77% of vaccinated adults say the statement “people who choose not to get a COVID-19 vaccine are hurting the country” describes them at least somewhat well. By contrast, 88% of those who have not received a vaccine say that “there’s too much pressure on Americans to get a COVID-19 vaccine” describes their own views very or somewhat well.

However, vaccinated adults are not without anxieties and concerns surrounding vaccines: 54% of this group says the statement “we don’t really know yet if there are serious health risks from COVID-19 vaccines” describes them very or somewhat well, and 50% say the same about the statement “it’s hard to make sense of all the information about COVID-19 vaccines.”

With the delta variant having changed the trajectory of the outbreak in the United States and around the world, large majorities continue to see a number of steps as necessary to address the coronavirus, including requiring masks for travelers on airplanes and public transportation (80%), restricting international travel (79%) and asking people to avoid gathering in large groups (73%).

The public is closely divided over limiting restaurants to carry-out and closing K-12 schools for in-person learning: About as many adults say these steps are unnecessary as say they are necessary.

Vaccination requirements for in-person activities have gone into effect in a number of U.S. cities, including New Orleans, New York City and San Francisco. A 61% majority of Americans favor requiring adults to show proof of vaccination before being allowed to travel by airplane. More than half also say proof of vaccination should be required to attend public colleges and universities (57%) and to go to sporting events and concerts (56%).

However, the public is less convinced that vaccine requirements are needed in other settings. Equal shares of Americans favor and oppose requiring proof of vaccination to eat inside of a restaurant (50% vs. 50%), and 54% say they oppose a vaccination requirement to shop inside stores and businesses.

The intertwined dynamics of partisan affiliation and vaccination status are visible in views of policies to limit the spread of the coronavirus and vaccine requirements. Democrats offer broad support for most measures, while Republicans back select steps – like limiting international travel and requiring masks on public transportation – while opposing others and offering very little support for vaccine mandates. Similarly, vaccinated adults are far more supportive of policy steps aimed at limiting the spread of the coronavirus – and vaccine requirements – than are those who have not received a COVID-19 vaccine.

Changes to public health guidance over course of outbreak: understandable, but also a source of concern for at least half of Americans

Over the course of the pandemic, public health officials have changed their recommendations about how to slow the spread of the coronavirus in the U.S.

A majority of Americans (61%) say changes to public health recommendations since the start of the outbreak have made sense because scientific knowledge is always being updated. About half (51%) say these changes have reassured them that public health officials are staying on top of new information.

However, changes to public health guidance have also sparked confusion and skepticism among significant shares of the public: 55% say changes made them wonder if public health officials were holding back important information, 53% say it made them feel confused and 51% say it made them less confident in officials’ recommendations.

Taken together, 63% of U.S. adults say they’ve felt at least one of two negative reactions regarding public health officials because of changing guidance: wondering if they were holding back important information or feeling less confident in their recommendations.

Mask wearing – among the most visible examples of shifting public health guidance, as well as a policy flashpoint at the state and local level – has become less frequent since earlier this year. Overall, 53% of U.S. adults say they’ve been wearing a mask or face covering all or most of the time when in stores and businesses over the last month, down 35 percentage points from 88% who said this in February (when mask requirements around the country were more widespread).

The practice of mask wearing is now far more common among Democrats and those who have been vaccinated against COVID-19. Democrats are now more than twice as likely as Republicans to say they’ve been wearing a mask in stores and businesses all or most of the time in recent weeks (71% vs. 30%). In February, large shares of both Democrats and Republicans had reported frequent mask wearing (93% and 83%, respectively).

People who have received a COVID-19 vaccine (59%) are more likely than those who have not (37%) to say they’ve been wearing a mask all or most of the time when inside stores or businesses. Frequent mask wearing is especially high among those who say they are very concerned about getting a serious case of the disease (80%).

Black adults about as likely as White adults to have received a COVID-19 vaccine

Vaccination rates differ across key demographic groups and traits, including age, family income, partisanship, health insurance status, community type and religious affiliation.

Comparable majorities of Black (70%) and White (72%) adults have received at least one dose of a COVID-19 vaccine. Among Hispanic adults, 76% say they have received a vaccine, as do an overwhelming majority of English-speaking Asian adults (94%). 

At earlier stages of the outbreak, Black adults had expressed significantly lower levels of intent to get a COVID-19 vaccine than White adults.

The vaccination rate among White evangelical Protestants continues to lag behind those of other major religious groups: 57% of White evangelicals say they have received at least one dose of a COVID-19 vaccine, compared with 73% of White Protestants who are not evangelicals, 75% of religiously unaffiliated adults and 82% of Catholics. For more details on vaccination status by religion, see the Appendix .

Older adults remain more likely than younger adults to have received at least one dose of a COVID-19 vaccine. Age differences in vaccination status are much more pronounced among Republicans and Republican leaners than among Democrats and Democratic leaners. See the Appendix for more details.

These are among the principal findings from Pew Research Center’s survey of 10,348 U.S. adults conducted from Aug. 23 to 29, 2021, on the coronavirus outbreak and Americans’ views of a COVID-19 vaccine. The survey also finds:

39% say most businesses in the U.S. should require employees to get a COVID-19 vaccine. Another 35% say businesses should encourage employees to get a vaccine, but not require it. A quarter of the public says most businesses should neither require nor encourage employees to get a COVID-19 vaccine. The survey was fielded before President Joe Biden’s announcement that employers with more than 100 workers will be required to have their workers vaccinated or tested weekly for the coronavirus.

72% say they personally know someone who has been hospitalized or died from COVID-19. As has been the case throughout the outbreak, larger shares of Black (82%) and Hispanic (78%) adults than White (70%) and English-speaking Asian adults (64%) say they personally know someone who has been hospitalized or died as a result of the coronavirus. 

A relatively small share of Americans (26%) are aware that few adults in developing countries have access to COVID-19 vaccines. A majority (76%) places importance on the U.S. providing large numbers of COVID-19 vaccines to developing countries, though just 26% call this a top priority for the U.S.

Biden’s job ratings for handling the outbreak have declined. Larger shares now say Joe Biden is doing an only fair or poor job (52%) responding to the coronavirus outbreak than say he is doing an excellent or good job (47%). In February, 54% said he was doing an excellent or good job. By contrast, Americans continue to give very high marks to hospitals and medical centers in their area: 85% say they are doing an excellent or good job responding to the coronavirus outbreak.

Republicans grow more skeptical of scientists’ judgment. Nearly seven-in-ten Republicans (68%) say scientists’ judgments are just as likely to be biased as other people’s, up from 55% who said this in January 2019. By contrast, a growing share of Democrats take the opposite view and say scientists make judgments solely on the facts (73% of Democrats say this today, up from 62% in 2019).

Large partisan gap persists in whether COVID-19 poses serious public health threat

A majority of Americans (61%) continue to say the coronavirus outbreak poses a major threat to the health of the U.S. population as a whole. Another 33% say the virus is a minor threat, while just 6% say it is not a threat.

The share that views the coronavirus as a major threat to public health has largely held steady since late March of 2020, following the declaration of a national public health emergency in the U.S. The current share that views the coronavirus as a major threat to public health is about the same as it was in February 2021 (63%), when the country was coming out of a peak of cases and COVID-19-related deaths, and before widespread rollout of the vaccine.

A larger majority of U.S. adults (72%) say the coronavirus outbreak is a major threat to the U.S. economy. This is down slightly from February of this year, when 81% saw the outbreak as a major threat to the economy.

Large partisan divides persist in views of the public health threat posed by COVID-19. Eight-in-ten Democrats and independents who lean toward the Democratic Party say the outbreak is a major threat to the health of the U.S. population, while just 38% of Republicans and Republican leaners say the same. The partisan gap on this question is as wide as it has been at any point during the pandemic.

By contrast, majorities of both Democrats (75%) and Republicans (69%) see the COVID-19 outbreak as a major threat to the country’s economy. While economic concerns remain high, the shares of both parties who see the virus as a serious concern for the economy have moved lower since February, when 83% of Democrats and 81% of Republicans said it was a major threat.

Vaccination status is closely tied to perceptions of the public health threat posed by the coronavirus outbreak: 70% of vaccinated adults view it as a major threat to the health of the U.S. population, compared with just 37% of adults who have not received a vaccine. There is shared concern over the impact on the economy, however: Majorities of both vaccinated (74%) and unvaccinated (67%) adults say the coronavirus poses a major threat to the U.S. economy.

Hospitals, medical centers continue to receive positive ratings for their outbreak response; Biden’s ratings decline

The public continues to rate the job their local hospitals have done responding to the coronavirus very positively; these ratings have been consistently high since the early days of the pandemic. Ratings for President Joe Biden’s handling of the outbreak have declined since February and now tilt more negative than positive. Assessments of other groups, including public health officials and state and local elected officials, are steady since February, but remain lower than they were in the early stages of the outbreak.

Overall, 47% say Biden is doing an excellent or good job responding to the coronavirus outbreak, while slightly more (52%) say he is doing an only fair or poor job. Ratings for Biden have declined since February, shortly after he took office, when 54% said he was doing an excellent or good job.

A large majority of Americans (85%) say their hospitals and medical centers are doing an excellent or good job responding to the coronavirus outbreak, identical to the share who said this in February 2021.

Six-in-ten say public health officials, such as those at the Centers for Disease Control and Prevention (CDC), are doing an excellent or good job in their coronavirus response. This rating is lower than it was during the early months of the outbreak, but about the same as it was in February of this year (62%).

A majority of Americans (56%) also say that their local elected officials are doing an excellent or good job responding to the outbreak. A slightly smaller share (50%) rate their state elected officials’ responses as excellent or good. As with ratings of public health officials, assessments of local and state elected officials are lower than they were early in the outbreak, but are about the same as they were when the questions were last asked six months ago.

Republicans and Democrats share positive assessments of the COVID-19 response from their local hospitals and medical centers but differ widely on the job public health officials and Biden are doing.

Large majorities of Republicans (83%) and Democrats (88%) say hospitals and medical centers in their area are doing an excellent or good job responding to the coronavirus outbreak.

By contrast, a much larger share of Democrats (79%) than Republicans (37%) give positive ratings to the job public health officials, such as those at the CDC, have done responding to the outbreak. Ratings of public health officials among Republicans are down 7 percentage points since February; as a result, the partisan gap in assessments of public health officials has grown even wider (from 35 points to 42 points in the current survey).

Partisan divides are even larger for ratings of Biden. About three-quarters of Democrats (74%) say he is doing an excellent or good job responding to the coronavirus pandemic, compared with just 15% of Republicans – a 59-point gap. Ratings of Biden are down among both parties since February, when 84% of Democrats and 20% of Republicans rated his performance highly.

The size of the partisan gap in ratings of Biden is similar to differences seen in ratings of former President Donald Trump at the end of his administration. In February , 71% of Republicans said he did an excellent or good job responding to the pandemic during his time in office, compared with just 7% of Democrats.

There are modest differences between Republicans and Democrats in assessments of how their local and state elected officials are handling the outbreak. Democrats are somewhat more likely than Republicans to rate the job being done by local officials (60% vs. 53%) and state elected officials (55% vs. 45%) as excellent or good.

54% of Americans say worst still to come from coronavirus outbreak

Thinking about the problems the country is facing from the outbreak, a narrow majority (54%) says they think the worst is still to come, while 45% say the worst is behind us.

Views are more positive than they were in November 2020 – before COVID-19 vaccines were approved for use in the U.S. – when just 28% of Americans thought the worst was behind us and 71% said the worst was still yet to come.

Republicans and Republican leaners are slightly more optimistic about the state of the outbreak than Democrats and Democratic leaners: 53% of Republicans say the worst is behind us, while 59% of Democrats take the opposing view and think the worst is still to come.

Adults who have received at least one dose of a coronavirus vaccine and those who have not view the state of the coronavirus outbreak in similar terms: 53% of vaccinated and 56% of unvaccinated adults say the worst of the problems from the outbreak are still to come.

The toll of restrictions on public activity are widely felt, but majority in U.S. sees public health benefits as worth the cost

Nearly all adults in the U.S. say that coronavirus-related restrictions on public activity have hurt businesses and economic activity either a lot (69%) or some (26%); just 5% say these restrictions have hurt businesses not too much or not at all.

Large shares also say restrictions on public activity have kept people from living their lives the way they want either a lot (58%) or some (31%).

Americans are less convinced of how much the restrictions have helped to prevent hospitalizations and deaths from the coronavirus and helped to slow its spread. Majorities say the restrictions have helped at least some in each regard, but only about three-in-ten say they have done a lot to help prevent hospitalizations and deaths from COVID-19 (32%) or slow the spread of the coronavirus (31%).

Nonetheless, when asked to assess the overall impact of the restrictions on public activity, a majority of Americans (62%) say the public health benefits have been worth the costs; significantly fewer (37%) say they have not been worth the costs.

Vaccinated adults (those who have received at least one dose of a coronavirus vaccine) are less likely than those who have not received a vaccine to say restrictions on public activity have done a lot to hurt businesses and keep people from living their lives, and they are more likely to say restrictions have done a lot to help prevent serious illnesses and slow the virus’s spread. For example, 40% of vaccinated adults say restrictions have helped a lot to prevent hospitalizations and deaths from the virus, compared with just 12% of unvaccinated adults who say the same.

These two groups arrive at differing conclusions about the overall impact of the restrictions: 73% of vaccinated adults say the public health benefits of the restrictions have been worth the costs, while 33% of those not vaccinated say this. A majority of those not vaccinated (65%) say the health benefits of the restrictions have not been worth the costs.

There are also wide differences in views of the public health restrictions by partisanship, with Republicans being more likely than Democrats to say the restrictions have had negative impacts, and less likely to say they have helped a lot to prevent severe illnesses and slow the spread of the coronavirus.

Majorities in U.S. back proof of vaccination for air travel, college students

As several cities and businesses around the country have begun requiring customers to show proof of COVID-19 vaccination to do things like eat at restaurants or attend concerts , Americans offer mixed views of these requirements, with opinion ranging from majority support to opposition, depending on the setting.

About six-in-ten Americans (61%) say they favor requiring adults in the U.S. to show proof of COVID-19 vaccination before being allowed to travel by airplane, while 38% would oppose such a requirement. While some U.S. airlines have required their employees to get vaccinated , they have so far stopped short of requiring proof of vaccination from travelers – although some destinations, such as Hawaii , require visitors to either show proof of vaccination or a negative coronavirus test result, or else quarantine for 10 days after arrival.

As the school year begins around the country, just under six-in-ten Americans (57%) say they favor requiring proof of COVID-19 vaccination for students to attend public colleges and universities in person. More than 800 U.S. colleges are requiring vaccinations for students and staff to be on campus, and more are strongly encouraging vaccination.

A narrow majority of adults (56%) also support requiring proof of COVID-19 vaccination in order to attend sporting events or concerts.

The public is evenly split over whether they would support or oppose being made to show proof of vaccination to eat inside of a restaurant. Some cities, such as New York , have required restaurants and bars to ask for proof of vaccination in response to rising infections and hospitalizations.

On balance, the public leans against requiring proof of vaccination to shop inside stores and businesses: 54% say they are opposed to this, while 45% support such a requirement.

Partisanship, as well as vaccination status, plays a large role in views about requiring coronavirus vaccines. Majorities of Democrats favor requiring adults to show proof of vaccination before doing all five of the activities included in the survey; by contrast, majorities of Republicans oppose each of these measures.

For example, 77% of Democrats and independents who lean toward the Democratic Party favor requiring those going to a sporting event or concert to show proof of vaccination, while 68% of Republicans and Republican leaners oppose requiring spectators to prove they’ve received a coronavirus vaccine.

Not surprisingly, adults who have not received a vaccine overwhelmingly oppose requiring proof of vaccination in these settings; roughly eight-in-ten or more oppose each of the five activities requiring proof of vaccination. Among those who have received at least one dose of a vaccine, majorities support requiring proof of vaccination, though the level of support varies from 56% for shopping inside stores and businesses to 77% for travel by airplane.

Differences in views by vaccination status exist within partisan groups. Among Republicans and Republican leaners, 55% of vaccinated Republicans favor requiring proof of vaccination for air travel, compared with 12% of unvaccinated Republicans. Just under half of vaccinated Republicans back proof of vaccination for attending events and public colleges and universities (compared with only about 10% of unvaccinated Republicans). However, when it comes to requirements to eat inside restaurants or shop, majorities of Republicans, regardless of vaccination status, oppose having to provide proof of vaccination. (60% of Republicans and Republican leaners are vaccinated; 38% are not.)

Among Democrats and Democratic leaners, differences are even wider, with majorities of vaccinated Democrats in favor of requiring proof of vaccination in all five settings and majorities of unvaccinated Democrats opposed to all five requirements. However, those who have not received a vaccine represent a small share of all Democrats (14%), compared with 38% among Republicans.

Requiring masks on transit, restricting international travel, avoiding large gatherings widely seen as necessary steps to address coronavirus

When asked about policies in place in some areas of the country to address the coronavirus outbreak, 80% of Americans say they think it is necessary to require masks for people traveling on airplanes or public transportation. A similar majority (79%) says it is necessary to restrict international travel to the U.S.

About three-quarters of U.S. adults (73%) also think asking people to avoid gathering in large groups is a necessary step to deal with the outbreak.

The public is closely divided on the necessity of two other policies: limiting restaurants to carry-out only (50% necessary, 50% unnecessary) and closing K-12 schools for in-person learning (48% necessary, 51% unnecessary). In-person learning has recently restarted at most schools around the country – although some schools have had to temporarily revert to remote instruction due to coronavirus outbreaks among students or staff.

The shares of Americans that support each of these measures have stayed relatively stable since the questions were last asked in February 2021 .

Vaccinated adults (including those who have received one of two vaccine doses) are more likely to see each of these five policies as necessary to address the outbreak than adults who have not received a vaccine.

For instance, 82% of vaccinated Americans think it is necessary to ask people to avoid gathering in large groups. About half of unvaccinated adults (49%) say this policy is necessary, while 51% say it is unnecessary.

There also are wide differences in views of policies aimed at addressing the coronavirus outbreak by partisanship, with Democrats expressing significantly more support for each policy than Republicans.

However, the magnitude of the partisan gap varies by policy.

For instance, majorities of Democrats (85%) and Republicans (73%) say it’s necessary to restrict international travel to the U.S. in order to address the coronavirus outbreak (a 12-point partisan gap).

By contrast, Democrats are far more likely than Republicans to say it is necessary to limit restaurants to carry-out only (68% vs 26%) and to close K-12 schools for in-person learning (67% vs. 25%).

Decline in share of U.S. adults who report frequent mask wearing

Public health guidance on mask wearing has changed over the course of the outbreak, and policies requiring masks – or preventing mask requirements – have varied widely at the state and local level.

In the current survey, 53% of adults say that in the past month they have worn a mask or face covering all or most of the time when in stores and businesses; 21% say they have worn one some of the time and 25% say they’ve worn a mask in these public places hardly ever or never.

The share of U.S. adults who say they’ve been wearing a mask all or most of the time is down 35 points since February, when mask mandates were more widely in place around the country than they are today. The decline in frequent mask wearing has been much greater among Republicans (down 53 points) than among Democrats (down 22 points). In February, there was a modest partisan divide on this question as large majorities of both Republicans (83%) and Democrats (93%) said they had been wearing a mask all or most of the time in public. Today, the partisan gap has grown dramatically to 41 points as Democrats are now far more likely than Republicans to report wearing a mask all or most of the time when in stores and businesses (71% vs. 30%).

Vaccinated adults are significantly more likely than those who have not received a COVID-19 vaccine to report frequently wearing a mask in public places.

About six-in-ten (59%) of those who have received at least one dose of a vaccine say they have been wearing a mask all or most of the time in stores and businesses over the last month. A much smaller share (37%) of those who have not received a COVID-19 vaccine report this level of mask wearing; 45% of this group say they have been wearing a mask in stores and businesses hardly ever or never in the last month.

There is a strong link between personal concern about getting a serious case of the coronavirus and mask wearing. Eight-in-ten of those who are very concerned about getting the coronavirus and requiring hospitalization say they’ve been wearing a mask all or most of the time in stores and businesses. The share who report frequent mask wearing falls to 64% among those who are somewhat concerned about getting a serious case of the coronavirus and to 38% among those who are not too or not at all about getting the coronavirus and requiring hospitalization.

Mask-wearing habits also differ significantly by the type of community where people live. Nearly seven-in-ten adults who live in urban areas (68%) say they’ve been wearing a mask all or most of the time in stores and businesses, compared with 51% of those in suburban areas and 42% of those in rural areas.

58% of Americans express concern about unknowingly spreading the coronavirus

A majority of Americans say they are either very (27%) or somewhat (32%) concerned that they might spread the coronavirus to other people without knowing that they have it. A smaller share (45%) say they are very (19%) or somewhat (26%) concerned that they will get the coronavirus and require hospitalization.

Concern over getting and unknowingly spreading the coronavirus has gradually edged lower since the start of the pandemic. In April 2020, 66% of U.S. adults were at least somewhat concerned about unknowingly spreading the coronavirus (including 33% who were very concerned); at that time, 55% were at least somewhat concerned about getting a serious case themselves (24% very concerned).

There are wide differences in levels of concern over getting and spreading the coronavirus by vaccination status as well as by other characteristics such as party affiliation and race and ethnicity.

About two-thirds of vaccinated adults are very (31%) or somewhat (35%) concerned about unknowingly spreading COVID-19 to others. Half are at least somewhat concerned about getting a serious case themselves. By contrast, among those who have not received a vaccine, fewer than half express concern about unknowingly spreading the coronavirus (38%) or getting a serious case themselves (32%), including relatively small shares who say they are very concerned about this (16% and 13%, respectively).

Democrats and Democratic-leaning independents are far more likely than Republicans and Republican leaners to say they are very or somewhat concerned about spreading the coronavirus to other people without knowing they have it (76% vs. 38%) and to say they are concerned about getting a serious case of the coronavirus themselves (56% vs. 30%).

White adults are much less likely than Black, Hispanic and English-speaking Asian adults to express concern over spreading the coronavirus or getting the coronavirus and requiring hospitalization. Eight-in-ten English-speaking Asian adults, 73% of Hispanic adults and 65% of Black adults say they are very or somewhat concerned about unknowingly spreading the coronavirus to others, compared with 52% of White adults.

Among White adults, Democrats are far more likely than Republicans to express concern about getting or spreading COVID-19. For instance, nearly three-quarters of White Democrats (74%) say they are very or somewhat concerned about unknowingly spreading the coronavirus, compared with 35% of White Republicans. (Overall, larger shares of White adults than Black, Hispanic and English-speaking Asian adults identify with or lean toward the Republican Party.)

About seven-in-ten Americans have at least a fair amount of confidence in COVID-19 vaccine research and development process

Strong confidence in the vaccine research and development process has risen steadily over the past year. The share saying they have a great deal of confidence that the research and development process has produced safe and effective COVID-19 vaccines has increased 20 percentage points (to 39%) over the past year and is up 6 points since February.

A majority of Americans (72%) continue to say they have at least a fair amount of confidence that the research and development process has produced safe and effective COVID-19 vaccines.

As with earlier Center surveys, levels of confidence in the COVID-19 vaccine research and development process are strongly tied to vaccination status. Nearly all of those who have received at least one dose of a COVID-19 vaccine (91%) say they have at least a fair amount of confidence in the vaccine R&D process, including 52% who say they have a great deal of confidence.

By contrast, only 21% of those who are not vaccinated say they have at least a fair amount of confidence in the vaccine R&D process (including just 3% who have a great deal of confidence).

A larger majority of Democrats than Republicans say they have at least a fair amount of confidence in the vaccine research and development process (86% vs. 55%). Among Democrats, 54% express a great deal of confidence (just 22% of Republicans say the same).

Americans who are vaccinated and not vaccinated see COVID-19 vaccines in starkly different lights

The development of COVID-19 vaccines and their uptake among the U.S. public are the center of the public health strategy to combat the coronavirus outbreak.

When asked how well various statements about coronavirus vaccines describe them, the public expresses a mix of positive and negative sentiments. Overall, 73% of adults say that the statement “vaccines are the best way to protect Americans from COVID-19” describes their own views very or somewhat well; 27% say it describes their views not too or not at all well. A majority (60%) also say the statement “people who choose not to get a COVID-19 vaccine are hurting the country” describes their views at least somewhat well.

At the same time, sizable shares of the public express concerns regarding COVID-19 vaccines. About six-in-ten (61%) say the statement “we don’t really know yet if there are serious health risks from COVID-19 vaccines” describes their views very or somewhat well.

When it comes to information about vaccines, 54% align with the statement “public health officials are not telling us everything they know about COVID-19 vaccines,” and 55% say that “it’s hard to make sense of all the information about COVID-19 vaccines” describes their views well.

The public is about evenly split over the statement “there is too much pressure on Americans to get a COVID-19 vaccine”: 51% say this describes their views very or somewhat well, while 48% say it describes how they feel not too or not at all well.

Vaccinated adults are much more likely than those who are not vaccinated to say the sentiment that vaccines are the best way to protect Americans from COVID-19 describes them at least somewhat well (91% vs. 23%). There is a similarly large gap when it comes to expressing alignment with that view that people who choose not to get vaccinated are hurting the country (77% vs. 13%).

However, even among those who are vaccinated, some concerns about COVID-19 vaccines resonate: 54% of vaccinated adults say the statement “we don’t really know yet if there are serious health risks from COVID-19 vaccines” describes their views very or somewhat well. Taken together, 70% of vaccinated adults express alignment with at least one of four sentiments of confusion or concern about COVID-19 vaccines.

Those who have not received a COVID-19 vaccine are less likely to express cross-cutting attitudes about vaccines. Fewer than 25% say they are described at least somewhat well by the statements that vaccines are the best way to protect Americans from COVID-19 and that people who choose not to get a COVID-19 vaccine are hurting the country.

Vaccination status also matters within partisan coalitions when assessing views toward vaccines. Among Republicans who have received a vaccine, 83% say the statement “vaccines are the best way to protect Americans from COVID-19” describes their views very or somewhat well, and 56% say this about the statement “people who choose not to get a COVID-19 vaccine are hurting the country.” Republicans who have not received a vaccine express very low levels of alignment with these two statements. (Six-in-ten Republicans and Republican leaners have received at least one dose of a vaccine, while 38% have not.)

More than half of Republicans, regardless of vaccination status, say each of the four statements of confusion or concern regarding vaccines describes their views well, though larger majorities of unvaccinated than vaccinated Republicans express alignment with these statements.

There also are differences in these views by vaccination status among Democrats, with vaccinated Democrats more likely than unvaccinated Democrats to say they’re described well by positive sentiments toward vaccines; the opposite pattern is seen for sentiments expressing confusion or concern. However, unvaccinated adults make up a relatively small share of all Democrats and Democratic leaners: Just 14% of Democrats say they have not received at least one dose of a COVID-19 vaccine.

Fewer than half think businesses should require vaccines for employees, but a majority think they should at least encourage it

Asked to think about workplaces and COVID-19 vaccines, 39% of the public says most businesses should require their employees to get a vaccine, while another 35% say businesses should encourage employees to get a COVID-19 vaccine, but not require it. A quarter of the public says employers should neither require nor encourage employees to get vaccinated.

Views on this question differ only modestly by employment status. And among adults under 50, the same share of those employed and not employed say most businesses should require workers to get a vaccine (34%).

A majority of Democrats (59%) say most businesses should require employees to get a COVID-19 vaccine, compared with 17% of Republicans.

Those with higher levels of education are more likely to favor a vaccination requirement. Adults with a postgraduate education are 20 points more likely than those with high school or less education to support requirements (55% vs. 35%).

Most vaccinated adults are open to getting a COVID-19 booster shot

The share of the adult public that says they’ve received at least one dose of a vaccine for COVID-19 rose dramatically between February and June of this year (from 19% to 67%), as vaccines became more widely available. Since June, the share of adults who say they’ve received at least one dose of a COVID-19 vaccine has increased 6 points to 73%.

In recent weeks the Food and Drug Administration has approved booster shots – an additional dose of a COVID-19 vaccine – for people with weakened immune systems, and the FDA and CDC continue to evaluate the potential need for booster shots among the general public.

Adults who have already received at least one dose of a COVID-19 vaccine express broad openness to receiving a booster shot. A large majority of vaccinated adults (62% of the total public) say they would probably get a vaccine booster, if public health officials recommend an additional dose. A far smaller share of vaccinated adults (10% of the total public) say they would probably not get a vaccine booster.

Divides over vaccines play out among family and friends

Adults who have received a COVID-19 vaccine and those who have not report distinctly different input from their friends and family when it comes to the vaccination decision.

A majority of vaccinated adults (59%) say their close friends and family have mostly encouraged them to get a coronavirus vaccine. Just 3% of vaccinated adults say their close friends and family have mostly discouraged them from doing this; 26% say the input has been mixed and 12% say they haven’t heard much from friends and family about vaccines.

By contrast, among those who have not received a COVID-19 vaccine, just 11% say their close friends and family have mostly encouraged them to get a coronavirus vaccine; another 11% say they have been mostly discouraged by friends and family from getting a vaccine. Among those who have not been vaccinated, about half (49%) describe the input from their close friends and family as mixed, with some encouraging them to get a vaccine and some discouraging them from doing so; 28% say their close friends and family haven’t said much about vaccines.

There are also wide differences on this question by partisanship. Six-in-ten Democrats and Democratic leaners say their close friends and family have mostly encouraged them to get a vaccine, while 25% say they’ve received mixed input and just 4% say they’ve mostly been discouraged from getting a vaccine.

Republicans and Republican leaners are much less likely than Democrats and Democratic leaners to say their close friends and family have mostly encouraged them to get a coronavirus vaccine (31% vs. 60%). Among Republicans, 40% say the input they received from close friends and family has been mixed, while 22% say their friends and family haven’t said much. Relatively few (7%) say they’ve mostly been discouraged from getting a vaccine.

Americans hold mixed reactions to changing public health guidance during the coronavirus outbreak

Over the course of the outbreak, public health guidance on how to deal with the coronavirus has changed, including information on core concepts such as how the coronavirus spreads and how effective masks are at limiting the spread of the virus.

Americans express a mix of both positive and negative reactions when asked how this changing guidance has made them feel.

A majority (61%) says changes to public health recommendations since the start of the outbreak made sense because scientific knowledge is always being updated. About half (51%) say the changing guidance reassured them that public health officials are staying on top of new information.

At the same time, the public also expresses negative reactions: 55% say the changing guidance made them wonder if public health officials were holding back important information, and 51% say these changes made them feel less confident in public health officials’ recommendations. Taken together, 63% of U.S. adults express at least one of two negative reactions to changing public health guidance.

Confusion was also a reaction experienced by just over half of adults: 53% say changing recommendations over the course of the outbreak made them feel confused.

There are wide differences in reactions to changing guidance from public health officials by vaccination status and partisan affiliation.

U.S. adults who have not been vaccinated against COVID-19 are far more likely to express negative reactions to changes in guidance from public health officials than vaccinated adults. Large majorities of those who are not vaccinated say changing recommendations made them wonder if public health officials were holding back important information (78%) and say it made them feel less confident in public health officials’ recommendations (75%). Fewer than half of vaccinated adults express either of these two sentiments (47% and 43%, respectively).

Those who have been vaccinated are far more likely than those who have not to say changes to recommendations made sense because scientific knowledge is always being updated (72% vs. 32%).

There are comparably large differences by partisan affiliation in reactions to changes in public health recommendations, with Democrats more likely to express positive feelings and Republicans more likely to express negative reactions. For instance, Democrats are 41 points more likely than Republicans to say changes in recommendations made sense because scientific knowledge is always being updated (80% vs. 39%). When it comes to negative reactions, Republicans are 35 points more likely than Democrats to say that changing guidance made them wonder if public health officials were holding back important information (74% vs. 39%). But Democrats do not express exclusively positive responses to shifts in public health recommendations: 47% say they’ve experienced at least one of the two negative reactions to changing guidance, and 44% say they’ve felt confused.

Higher educational attainment is also connected with more positive reactions to changing health guidance. For example, about three-quarters of Americans with a postgraduate degree (76%) say changing guidance made sense because scientific understanding is always being updated. This compares with 66% of college graduates, 59% of those with some college experience and 54% of those with a high school diploma or less education. Educational differences occur on this question among both Republicans and Democrats.

Those with lower levels of education are especially likely to express negative reactions to changing guidance: For instance, 60% of those with a high school diploma or less and 58% of those with some college say changing recommendations about how to slow the spread of the coronavirus made them wonder if health officials were holding back important information; this view is less widely held among college graduates (50%) and postgraduates (41%).

However, there is little difference across levels of education in having felt confused by changing guidance from public health officials, with between 49% and 55% of all groups expressing this view. See the Appendix for details.

Majority of Americans know someone who has been hospitalized or died from COVID-19

More than 600,000 Americans have died as a result of COVID-19, and millions have been hospitalized from the disease. In the current survey, 72% of U.S. adults say they personally know someone who has been hospitalized or died as a result of having COVID-19.

As has been the case throughout the outbreak, Black (82%) and Hispanic (78%) adults are especially likely to say they know someone who has been hospitalized or died as a result of the coronavirus. Majorities of White (70%) and English-speaking Asian adults (64%) also say they know someone who has been hospitalized or died.

Across other major demographic groups, there are modest or no differences in the shares who say they know someone who has been hospitalized or died as a result of COVID-19. Democrats and Republicans are about equally likely to say this (74% and 71%, respectively); there is a modest difference in this experience between adults who have received a COVID-19 vaccine and those who have not (74% vs. 68%).

A year and a half into the coronavirus outbreak in the U.S., three-in-ten U.S. adults say they have tested positive for COVID-19 or been “pretty sure” they had it.

There are differences by age, race and ethnicity, income and partisan affiliation when it comes to having had COVID-19. Younger Americans are more likely than their older counterparts to say they have had the coronavirus. Those ages 18 to 29 are about twice as likely as those 65 and older to report they tested positive or were “pretty sure” they had COVID-19 (36% vs. 17%).

Hispanic adults (39%) are more likely than Black (29%), White (28%) or Asian (21%) adults to say they have had COVID-19.

One-third of adults with lower incomes say they have tested positive for COVID-19 or been pretty sure they had it, compared with 24% of upper-income adults.

Republicans are modestly more likely than Democrats to say they have had COVID-19 (35% vs 27%).

Few Americans know access to vaccines is limited in developing countries

Many developing countries continue to have a low supply of COVID-19 vaccines, with small shares of their populations currently vaccinated. In African countries, for instance, it is estimated that just about 3% of the adult population has received a COVID-19 vaccination.

Asked about the status of COVID-19 vaccines in developing countries, about a quarter of Americans (26%) correctly say that very few adults in developing countries can currently get a vaccine, if they want one. Roughly four-in-ten Americans (42%) say that about half or most adults in developing countries have access to COVID-19 vaccines, while 32% say they aren’t sure.

When asked about the U.S. role in the global distribution of vaccines, about three-quarters of Americans (76%) say providing COVID-19 vaccines to developing countries should be at least an important priority, though only 26% of U.S. adults say it’s a “top” priority. About a quarter (23%) say this should be a lower priority or should not be done at all.

Those who are vaccinated are more likely to favor providing large numbers of vaccines to developing countries, a pattern that holds among both Republicans and Democrats. Overall, Democrats place a higher priority on providing vaccines to developing countries than Republicans.

Americans who are aware that most people in developing countries do not have access to COVID-19 vaccines, and those who see COVID-19 as a major threat to public health in the U.S., are relatively more likely to prioritize providing COVID-19 vaccines to developing countries.

Infectious disease researchers have argued that countries with low vaccination rates are more likely to develop new coronavirus variants. Reducing the risk of new coronavirus variants spreading to the country is seen as the main reason why the U.S. should provide vaccines to developing countries (among those who give this at least some level of priority).

Among the 90% of adults who say providing vaccines to developing countries is a top, important or lower priority, 72% say the main reason to do this is to reduce the risk of new variants spreading to the U.S. About two-in-ten (17%) say the main reason to do this is because the U.S. has an obligation to help people around the world get vaccinated.

About one-in-ten (9%) volunteer another rationale for why the U.S. should provide vaccines to developing countries. Common volunteered responses include that both reducing the risk of variants and a U.S. obligation to help are equally important reasons, that providing vaccines is the humanitarian choice, and that the U.S. should provide vaccines due to the country’s excess supply.

Republicans grow more skeptical that scientists base judgments solely on the facts

Americans are closely divided over whether scientists’ judgments are based solely on the facts or are just as likely to be biased as other people’s. In the current survey, 54% say scientists’ judgments are based solely on the facts, compared with 45% who think scientists’ judgments are just as likely to be biased as those of other people. These overall views are about the same as they were in 2019, the last time this question was asked.

However, Democrats have become more likely – and Republicans less likely – to say scientists’ judgments are based solely on the facts over the past two years. About three-in-ten Republicans and Republican leaners (31%) now say scientists’ judgments are based solely on the facts, down 13 percentage points since 2019. About seven-in-ten (68%) Republicans think scientists’ judgments are just as likely to be biased as those of other people.

Among Democrats and Democratic leaners, 73% say scientists’ judgments are based solely on the facts, up 11 points since 2019. The partisan gap in the share saying scientists’ judgments are based solely on the facts is now 42 points, much larger than the 18-point gap seen in 2019.

Recent Center surveys have also found growing political divides in confidence in scientists and views of the effect of science on society .

About seven-in-ten Americans see the scientific method as an iterative process

The survey also looked at Americans’ understanding of the scientific process. About seven-in-ten U.S. adults (71%) say the scientific method is an iterative process, with findings that are meant to be continually tested and updated, while 9% say the scientific method produces unchanging core principles and truths; 20% say they aren’t sure.

The share of Americans who see the scientific method as iterative is up slightly from November 2020 when 66% said this.

Americans with higher levels of education are more likely to say the scientific method produces findings meant to be continually tested and updated. About nine-in-ten (88%) of those with a postgraduate degree say this, compared with just 56% of those with a high school diploma or less. There are large educational differences on this question among both Democrats and Republicans.

CORRECTION (Sept. 15, 2021): A previous version of the chart “White evangelical Protestants, those with no health insurance among least likely to say they have received a COVID-19 vaccine” and a sentence in the report’s text misstated the share of White non-evangelical Protestants who have received at least one dose of a vaccine to prevent COVID-19. It should be 73% and has been updated to reflect that. 

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• Tom Buchanan   ORCID: orcid.org/0000-0002-2329-7893 1 ,
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Parents of racialized children and children with disabilities experience a unique set of challenges and stressors in their parenting role. Many studies now exist focusing on parenting during the pandemic. Yet, there is a need for more research examining how parenting during COVID is complicated for minority parents who have a child with a disability. For this project, we used the Crowdsourcing: Impacts of COVID-19 on Canadians-Parenting During the Pandemic, 2020 dataset. Data in this national survey was collected from June 9 to June 22, 2020 (Statistics Canada, 2020 a). We specifically examined how parenting at least one child with a disability intersected with being a racialized mother. After applying benchmarking and restrictions, the sample of 12,624 analyzed in this study consists non-Indigenous mothers with children either preschool age (0–5) or school age (6–14). The highest rates, across a broad range of concerns for children and family were reported by racialized mothers who also reported having child(ren) with a disability. Parents with only preschool children were less concerned for children but reported slightly higher levels of family concerns. A series of interactional analyses further revealed intersectional impacts on concerns between racialized mothers, parenting a child with a disability, and the age of the child. This study emphasizes the importance of intersectional considerations during the early pandemic relating to parenting for racialized mothers of children with disabilities. Societal implications, measurement/sample/analysis limitations, and policy implications are considered.

Racialized mothers (visible minorities) with at least one child with a disability experienced significantly higher parenting concerns for children and family during the COVID-19 pandemic than other groups.

Parents of preschool-age children had lower parenting concerns than parents of school-age children during the COVID-19 pandemic.

Understanding unique stressors experienced by racialized mothers with children with disabilities may provide opportunities for better community and service supports.

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Buchanan, T., Phung, N., Hammoud, M. et al. Parental Concerns during the COVID-19 Pandemic: Intersections for Racialized Mothers of Children with Disabilities. J Child Fam Stud (2024). https://doi.org/10.1007/s10826-024-02887-y

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74th session of the WHO Regional Committee for Europe

COVID-19 vaccinations have saved more than 1.4 million lives in the WHO European Region, a new study finds

Copenhagen, 16 january 2024.

Since their introduction in December 2020, COVID-19 vaccines have reduced deaths due to the pandemic by at least 57%, saving more than 1.4 million lives in the WHO European Region. Most of those saved were aged 60 or older, the group at highest risk of severe illness and death from the SARS-CoV-2 virus. The first vaccine booster alone saved 700 000 lives.

These are among the findings of a new WHO/Europe study revealing that today’s known COVID-19 death toll in the Region, currently at 2.5 million, might be as high as 4 million without the vaccines. 

“We have constantly stressed the importance of the COVID-19 vaccines, particularly for older people and the most vulnerable. This study documents the result of countries implementing that advice. The evidence is irrefutable,” said Dr Hans Henri P. Kluge, WHO Regional Director for Europe. 

Since the COVID-19 pandemic began, the Region, covering 53 Member States across Europe and central Asia, has seen more than 277 million confirmed cases and over 2.5 million recorded deaths.

The power of vaccines

“Today, there are more than 1.4 million people in our Region – most of them elderly – enjoying life with their loved ones because they took the vital decision to be vaccinated against COVID-19. That’s nearly 1.5 million people who can play with their grandchildren, walk the dog, attend dance classes, volunteer and be active members of their communities.

This is the power of vaccines,” Dr Kluge emphasized. 

The report reveals a 57% reduction in mortality among those aged 70–79 and a 54% decrease in deaths among those aged 60–69. Mortality was 52% lower in the 50–59 age group. The over-80 age group benefited the most from vaccination, with a 62% reduction in mortality.

Among those aged 25 to 49, receiving a second vaccine dose resulted in a 48% reduction in mortality, though the uptake of vaccines for the second and third boosters was just 5% in this group. In other words, even in this group, without vaccination the number of deaths would have been almost double.  

Mortality in countries reduced by up to 75%

The WHO/Europe study reveals that COVID-19 vaccination saved most lives during the period when the Omicron variant was dominant, from December 2021 to April 2023. 

In terms of impact on mortality in the Region as a whole, Israel saw the biggest benefits for all age groups with a 75% reduction, followed by Malta and Iceland with a 72% and 71% reduction, respectively. 

Broken down by age group, those aged 80 and older once again saw the most significant benefits from COVID-19 vaccination, with a reduction in mortality of 70% in Malta and 71% in the United Kingdom. 

Countries that implemented early vaccination programmes covering large parts of the population – such as Belgium, Denmark, Iceland, Ireland, Israel, Malta, the Netherlands and the United Kingdom – saw the greatest benefit in terms of the number of lives saved overall through vaccination. 

Learning to live with COVID-19

As winter intensifies in the northern hemisphere, cases of COVID-19 are once again on the rise, as are illnesses from other respiratory viruses including respiratory syncytial virus (RSV) and influenza. 

“COVID-19 hasn’t gone away. We have merely learned to live with it,” Dr Kluge said. “Much of society has acquired some level of immunity, either through vaccination, infection or both. Most of us are capable of assessing our own level of risk and our risk to others. And if we get sick with signs of COVID-19 or flu, most of us know it’s best to stay at home and away from others.”  

WHO/Europe’s report underlines the position of the European Technical Advisory Group of Experts on Immunization (ETAGE), which has consistently advised Member States to ensure that all eligible people are up to date with their COVID-19 vaccinations in line with national COVID-19 vaccination policies. 

Among the report’s sources are weekly counts of COVID-19 deaths and vaccine doses administered per age group, reported by 34 out of 53 Member States, areas and territories in the Region to the European Surveillance System (TESSy) between 2020 and March 2023. 

Ensuring our most vulnerable are protected

English couple Mervyn, 85, and Mary, 87, based in the United Kingdom, got their boosters after being invited by text message. They also make sure they get the influenza vaccine every year. “We’ve never had any problems with them. And if we did catch COVID or flu, it’s not likely to be as bad . . . I mean, they’re for your own protection and for the protection of other people,” said Mary.

Andrew, 75, and Max, 70 (who has a compromised immune system), also based in the United Kingdom, received their COVID-19 boosters at a dedicated vaccination centre set up in the grounds of a nearby racecourse. “We both got the booster to prolong the protection from serious illness that immunization offers and to reduce our chances of spreading the virus to others.”

You can see photos and read more by following the link . 

WHO/Europe Press Office

Estimated number of lives directly saved by COVID-19 vaccination programs in the WHO European Region, December 2020 to March 2023 (2024)

Coronavirus disease (COVID-19)

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• Published: 10 August 2024

Dynamic clade transitions and the influence of vaccination on the spatiotemporal circulation of SARS-CoV-2 variants

• Cecília Artico Banho 1 ,
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• Ana Karoline Sepedro Lima 1 ,
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• Alex Ranieri Jeronimo Lima 2 ,
• Gabriela Ribeiro 2 ,
• Antonio Jorge Martins 2 ,
• Claudia Renata dos Santos Barros 2 ,
• Maria Carolina Elias 2 ,
• Sandra Coccuzzo Sampaio 2 ,
• Svetoslav Nanev Slavov 2 , 3 ,
• Evandra Strazza Rodrigues 3 ,
• Elaine Vieira Santos 3 ,
• Dimas Tadeu Covas 2 , 3 ,
• Simone Kashima 3 ,
• Ricardo Augusto Brassaloti 4 ,
• Bruna Petry 4 ,
• Luan Gaspar Clemente 4 ,
• Luiz Lehmann Coutinho 4 ,
• Patricia Akemi Assato 5 ,
• Felipe Allan da Silva da Costa 5 ,
• Rejane Maria Tommasini Grotto 6 , 7 ,
• Mirele Daiana Poleti 8 ,
• Jessika Cristina Chagas Lesbon 8 ,
• Elisangela Chicaroni Mattos 8 ,
• Heidge Fukumasu 8 ,
• Marta Giovanetti 9 , 10 , 11 ,
• Luiz Carlos Junior Alcantara 9 , 10 ,
• Jayme A. Souza-Neto 12 ,
• Paula Rahal 13 ,
• João Pessoa Araújo Jr   ORCID: orcid.org/0000-0002-9153-1485 14 ,
• Fernando Rosado Spilki 15 ,
• Benjamin M. Althouse 16 , 17 ,
• Nikos Vasilakis 18 , 19 , 20 &
• Maurício Lacerda Nogueira   ORCID: orcid.org/0000-0003-1102-2419 1 , 18  

npj Vaccines volume  9 , Article number:  145 ( 2024 ) Cite this article

Metrics details

• Viral infection

Since 2021, the emergence of variants of concern (VOC) has led Brazil to experience record numbers of in COVID-19 cases and deaths. The expanded spread of the SARS-CoV-2 combined with a low vaccination rate has contributed to the emergence of new mutations that may enhance viral fitness, leading to the persistence of the disease. Due to limitations in the real-time genomic monitoring of new variants in some Brazilian states, we aimed to investigate whether genomic surveillance, coupled with epidemiological data and SARS-CoV-2 variants spatiotemporal spread in a smaller region, can reflect the pandemic progression at a national level. Our findings revealed three SARS-CoV-2 variant replacements from 2021 to early 2022, corresponding to the introduction and increase in the frequency of Gamma, Delta, and Omicron variants, as indicated by peaks of the Effective Reproductive Number (Reff). These distinct clade replacements triggered two waves of COVID-19 cases, influenced by the increasing vaccine uptake over time. Our results indicated that the effectiveness of vaccination in preventing new cases during the Delta and Omicron circulations was six and eleven times higher, respectively, than during the period when Gamma was predominant, and it was highly efficient in reducing the number of deaths. Furthermore, we demonstrated that genomic monitoring at a local level can reflect the national trends in the spread and evolution of SARS-CoV-2.

Introduction

Several SARS-CoV-2 variants have emerged over the course of the COVID-19 pandemic, driven by an unprecedented transmission rate and the rapid evolution of RNA virus genomes 1 , 2 , 3 . Lineages of SARS-CoV-2 harboring mutations associated with increased transmissibility, pathogenesis, and immune evasion began to appear in different countries in mid-2020. These emerging lineages have been classified by the World Health Organization (WHO) as variants of concern (VOC): Alpha 4 , Beta 5 , Gamma 6 , Delta 7 , and Omicron 8 .

These VOCs have replaced circulating strains, leading to subsequent waves of COVID-19 infection and healthcare system overloads, and the need of frequent vaccine updates 6 , 9 , 10 , 11 . The increasing number of cases from these new waves has reinforced the need for continuous genomic surveillance of SARS-CoV-2 12 , 13 , 14 . Studies on the epidemiology and the spatiotemporal history of SARS-CoV-2 transmission can effectively contribute to implementing real-time public health measures to contain the viral spread. While WHO has classified SARS-CoV-2 transmission and its disease as a continuous health problem, a robust genomic surveillance, variant identification, and the evaluation of their pathogenic potential, are fundamental elements for policymaking and disease containment 3 , 10 .

Brazil was an epicenter of the COVID-19 pandemic, and by June 2024, it had recorded 38,815,115 cases and 712,258 deaths 15 . In order to contain or mitigate the pandemic effets, in January 2021 Brazil started the vaccination campain and as of April 2022 76% of the Brazilian population have received two doses of vaccines against COVID-19 16 . In early 2021, the Brazilian Health Regulatory Agency (ANVISA) approved the use of four vaccines, CoronaVac (Sinovac TM /Institute Butantan) and AZD1222 (AstraZeneca/Oxford’s TM ) in January 2021; followed by BNT162b2 (Pfizer/BioNtech TM ) and Ad26.COV2.S (Johnson/Janssen TM ) 16 . The vaccines distribution occurred in phases, and it was first administered on people aged ≥60; institutionalized disabled people; indigenous, and health workers 16 . Since the start of Brazilian vaccination campain, several hindrances were observed, due to the high territorial extension of the country, making difficult to deliver vaccines, contributing a delayed vaccination program, as well as low adherence to vaccination, in some regions, due to political issues 17 . In addition to slow vaccination rates, resources for real-time genomic surveillance were limited in most Brazilian states, which makes identifying the emergence of regional variants or mutations challenging in a country the size of Brazil. One strategy to address this challenge is to monitor the lineages that circulate in a smaller region, such as a midsize city, which can reflect the Brazilian epidemiological landscape. São José do Rio Preto (SJdRP) is a suitable location for such monitoring, as the city presented the third highest number of COVID-19 cases and deaths in the state of São Paulo (SP) 18 . Furthermore, it housed one of the country’s largest and most significant hospital complexes, the Hospital de Base de São José do Rio Preto (HB). This reference center, serving more than two million inhabitants, was at the forefront of COVID-19 care and treatment for the state 19 and, with its constant exchange of SARS-CoV-2 variants, serves as an important model for visualizing and predicting viral transmission patterns. Here, we investigated how the introduction and spread of different SARS-CoV-2 VOCs combined with vaccination rollout have shaped the progression of COVID-19 in a single health district in northwestern São Paulo state.

SARS-CoV-2 variant report

São Paulo state recorded the highest numbers of COVID-19 cases and deaths in Brazil 15 , 18 in response to that, the São Paulo State Network for Pandemic Alert of Emerging SARS-CoV-2 Variants (SPNPAESV) was implemented in early 2021 to monitor the real-time evolution of circulating VOC and variants of interest (VOI) within the state. São Paulo state is divided into 17 regional health districts by the State Secretary of Health (SES-SP), facilitating the planning and articulation of health policies in alignment with the Brazilian national public health system ( Sistema Único de Saúde , SUS) 20 . Owing to substantial efforts from various research centers across each regional district, the SPNPAESV successfully sequenced 3,306 complete SARS-CoV-2 genomes from the Regional Health District (RHD) XV encompassing 102 cities, including SJdRP in the northwestern part of São Paulo state (Fig. 1A ).

A Map of Brazil showing the number of COVID-19 cases reported in the municipalities from the 15th Regional Health District (RHD XV) in northwestern São Paulo state from January 2021 to April 2022. B Map of São Paulo state showing the number of sequenced genomes obtained from the municipalities from the RHD XV from January 2021 to April 2022. C Prevalence of SARS-CoV-2 lineages detected in the municipalities from the RHD XV from January 2021 to April 2022 by genomic surveillance.

In our study, SARS-CoV-2 sequences from 85 cities were included (Fig. 1B ); sequences from SJdRP were the most representative, accounting for 29.3% of the sequenced genomes, and a total of 14 SARS-CoV-2 lineages were detected from January 2021 to April 2022. Of these lineages, the VOCs comprised most of the sequenced genomes, with Gamma being the most prevalent ( n  = 2,227, 67.48%), followed by Omicron ( n  = 600, 18.18%) and Delta ( n  = 381, 11.5%). Interestingly, the circulation of the Alpha variant ( n  = 1, 0.42%) was limited in the sampled municipalities. Other lineages, mostly detected in early 2021, were present at a low frequencies, including Zeta ( n  = 38, 1.15%), B.1.1.28 ( n  = 18, 0.54%), B.1.1.33 ( n  = 4, 0.12%), and others such as B.1, B.1.1, B.1.2, B.1.1.332, B.1.1.393, N.9, and P.4 ( n  = 18, 0.54%) (Fig. 1C , Supplementary Table 1 ).

Analyzing the distribution of SARS-CoV-2 lineages over time in the municipalities within the RHD XV, we observed that Zeta was the prevalent VOI in January 2021 (58.32%) and co-circulated with the other five variants (Supplementary Table 1 ). The introduction of Gamma was detected in late January; from then on, we observed the replacement of nearly all the other circulating SARS-CoV-2 variants, along with a sharp increase in COVID-19 case numbers (Fig. 2A ). Consequently, from March to September 2021, the VOC Gamma (P.1 and its sub-lineages) was the predominant lineage within the RHD XV. We identified the introduction of the Delta VOC in early August 2021 (in the city of Jales). This variant rapidly increased in frequency, replacing the Gamma variant by October of that year. Delta remained the predominant variant from October to December 2021, until it was displaced by Omicron (Fig. 2A ). By analyzing Brazilian sequences from the same period, we observed a similar pattern of Gamma dominance and an increase in the national COVID-19 case numbers in early 2021 (Fig. 2B ). This wave was followed by Delta replacement, which did not correspond to an increase in detected cases or death rates (Fig. 2B, D ). Omicron’s subsequent introduction and spread towards the end of 2021 led to an unprecedented surge in COVID-19 cases, accompanied by only a modest increase in deaths (Fig. 2A-D ).

Proportion of SARS-CoV-2 lineages circulating over time and associations with the moving average of COVID-19 cases reported in municipalities from the 15 th regional Health District (RHD XV) ( A ) and Brazil ( B ); Vaccination coverage and its effect on the number of deaths reported in the RHD XV ( C ) and Brazil ( D ).

Interestingly, despite Delta replacing Gamma in October 2021, there was no corresponding increase in case numbers. This scenario changed in December 2021 with the detection of Omicron, leading to a noticeable shift in case trends (Fig. 2A, B ). Reinforcing these findings, the analysis of effective reproduction number (Reff) revealed peaks (Reff > 1) from March to April 2021, late September 2021, and December 2021 to January 2022, indicating a higher transmission rate (Fig. 3A, B ). This increase in Reff corresponds with the introduction and growth in frequency of the Gamma, Delta, and Omicron VOCs in RHD XV municipalities and across Brazil (Fig. 3A, B ). Notably, even though a large number of cases were reported from January 2022, death only marginally increased. This trend is likely due to the nature of reported cases rather than increased disease severity, contrasting with the period of Gamma dominance and reinforcing the protective effect of vaccination coverage (Fig. 2C, D ).

A Incidence of COVID-19 per 100,000 inhabitants in the RHD XV region on the left y-axis together with estimated effective reproductive number (Reff) for all COVID-19 cases in the region, represented as a blue line on the right y-axis; ( B ) COVID-19 incidence per 100,000 inhabitants for all cases across Brazil and estimated effective reproductive number (Reff) over time (blue line) for all reported COVID-19 cases (right y-axis), including the percentage of vaccine coverage in the entire population during the same timeframe (left y-axis).

To further analyze the role of vaccination in Brazil relative to VOC dominance, we looked at the vaccine effectiveness for every 10% increase in overall vaccination uptake in terms of cases and death numbers, adjusting for the number of tests administered (Fig. 4A ). We found that vaccine effectiveness in preventing cases during the period dominated by Delta and Omicron (1 August – 1 November 2021 and 1 December 2021−30 April 2022, respectively) were six and 11 times higher than when Gamma was the dominant variant (1 February−31 July 2021). Similarly, vaccine effectiveness in preventing deaths during Delta’s dominance was higher than Gamma’s. However, vaccination showed no statistical effect in preventing deaths during Omicron’s dominance, which could be anticipated if the case fatality rate varied over time independent of vaccination. This variation is illustrated in Fig. 4B , where the deaths-to-case ratio decreased from 2.96% (95% CI: 2.77, 3.14) before December 2021 to 0.36% (95% CI: 0.31, 0.41) from December 2021 onwards.

A Effectiveness of accination per 10% increase in vaccination uptake in preventing new COVID-19 cases and deaths in Brazil. B Number of new deaths per new cases observed in 2021 and 2022 in Brazil. VE: Vaccine effectiveness.

SARS-CoV-2 phylodynamic analysis in the RHD XV region

To better understand the dynamics of SARS-CoV-2 lineages and their spread in the study area, we investigated the phylodynamics of the different lineages detected in the RHD XV and the lineages circulating in Brazil during the sampled period. We reconstructed a time-scaled maximum likelihood (ML) tree using 1227 genomes from all Brazilian states and 3300 genomes from 85 cities from the RHD XV sequenced in this study (Fig. 5A , Supplementary Table 2 ). Phylogenetic analysis showed three main clades corresponding to the Gamma, Delta, and Omicron variants depicted the clade replacement events over time in Brazil. Importantly, in the different clades, we observed that RHD XV sequences were interspersed with Brazilian sequences from different geographic regions, suggesting several introduction events in the RHD region (Fig. 5A ).

A Time-stamped phylogenetic tree reconstructed using 4527 Brazilian complete genomes (3300 from this study) (Supplementary Table 2 ) and linear regression of root-to-tip genetic distance of different SARS-CoV-2 lineages versus sampling date. Colors represent different lineages and tip shapes represent different locations. B Time-stamped phylogenetic tree reconstructed using 3300 genome sequences from the RHD XV region, including 962 from SJdRP (Supplementary Table 1 ) and linear regression of root-to-tip genetic distance of different SARS-CoV-2 lineages versus sampling date. Colors represent different lineages and tip shapes represent different locations.

Similarly, to understand the dynamics of SARS-CoV-2 within the region of study, we built a time-scaled ML tree including only sequences from the RHD XV (Supplementary Table 1 ). Sequences from SJdRP were highlighted since this municipality had the most significant number of cases, sequenced genomes (Fig. 1A, B ), and played an essential role during the COVID-19 pandemic. In the RHD XV Maximum Likelihood (ML) tree, we observed the clustering of sequences into three distinct groups, corresponding to the primary lineages of the virus identified in 2021 (Fig. 5B ). Additionally, the sequences from SJdRP were found distributed across various clades, along with sequences from other cities in the RHD XV region (Fig. 5B ), suggesting multiple virus importation and exportation from these areas.

Spatiotemporal dispersion of the Gamma, Delta, and Omicron lineages

Based on our spatiotemporal analyses, we could infer the number of virus exchanges between the RHD XV and the Brazilian regions and between SJdRP and surrounding cities within the RHD XV region. We found that cities in the RHD XV exchanged SARS-CoV-2 variants with all country regions (Fig. 6A , Supplementary Table 3 ). The Northeast region of Brazil contributed with the highest number of imported virus variants to the RHD XV region (at least 51 importations) ( p  < 0.001, X 2  = 28.516, df = 4) compared to all other regions, follwed by Southeastern states (at least 42 importations) (Fig. 6B ). Interestingly, most of viral importations from Northeastern Brazil occured in January 2021 (23%), and from several states such as Bahia, Alagoas, Ceará and Pernambuco. In contrast, most variants exported from the RHD XV region were sent to the southeast, accounting for at least 33 exportation events (Fig. 6B , Supplementary Table 3 ). Analysis of transmission dynamics within the RHD XV showed that SJdRP contributed to virus exchange during 2021 (Fig. 6C ). Most virus exchange were exports from SJdRP to other municipalities (at least 157). Interestingly, most of the importation events (at least 120) took place between April and August 2021, coinciding with the wide circulation of the Gamma variant in the RHD XV region (Fig. 6C , Supplementary Table 3 ).

A Number of all SARS-CoV-2 lineages exchanged between RHD XV municipalities and all Brazilian regions (North, Northeast, Midwest, Southeast, and South) from 2021 and early 2022. B Source of viral exports and imports of all SARS-CoV-2 lineages identified in 2021 and early 2022 from Brazil to cities in RHD XV and ( C ) from RHD XV to SJRP. Phylogeographic reconstruction and dispersion of the ( D ) Gamma variant, ( E ) Delta variant, and ( F ) Omicron variant in Brazil and in RHD XV municipalities. Shaded areas represent the 80% highest posterior density interval and depict the uncertainty of the phylogeographic estimates for each node. Curved lines show the links between nodes and viral movement to different locations. Circles represent nodes of the maximum clade credibility phylogeny, and their colors represent the inferred time of occurrence.

Next, we investigated the spatiotemporal history of the VOCs involved in the three major clade replacement events that were responsible for at least two significant COVID-19 epidemic waves in Brazil during 2021. Our phylogeographic analyses traced the movement of the Gamma lineage across the different Brazilian regions and its interaction with the RHD XV region. This analysis revealed that the Gamma variant was a prominent presence in Brazil’s epidemiological landscape throughout the period it was prevalent. Additionally, our findings suggest that the initial Gamma sequences identified in the RHD XV region were likely imported from Brazil’s southeastern and northeastern states (Fig. 6D ). Moreover, we observed a notable migration pattern for the Gamma lineage within the RHD XV region. The evidence suggests that this variant was first introduced in SJdRP and then rapidly spread to other municipalities, with a pronounced spread to neighboring cities (Fig. 6D ).

The Delta variant, which started to replace the Gamma variant in Brazil and specifically in the RHD XV region by September 2021 (Fig. 2A, B ), exhibited intense spread across all Brazilian regions. It notably moved between the southeastern, northeastern, and northern states and the RHD XV region (Fig. 6E ). However, when analyzing virus movement through the RHD XV region, we observed a predominance of exportation events from SJdRP, but to a lesser extent compared to Gamma, which may reflect the lower number of cases identified in that period (Fig. 6E ).

Importation and exportation of Omicron were observed among the RHD XV region and a few states in all Brazilian regions (Fig. 6F ). As with Delta, Omicron spread mainly from SJdRP to several cities within the RHD XV region (Fig. 6C, F ); despite the large number of cases reported after the introduction of Omicron, fewer importation and exportation events were observed compared to Gamma, which could suggest that most transmission occurred locally.

In a continent-spanning country like Brazil, limitations on real-time surveillance of SARS-CoV-2 variants have been reported due to different regional sequencing efforts 21 , which posed a severe challenge to monitor the origin of new mutations that may enhance virus fitness and persistence of the pandemic at the national level. A possible alternative is to implement genomic surveillance in a small region that exhibits constant virus exchange with several geographic locations and may reflect the progression of the pandemic nationally.

Our findings demonstrated successive clade replacement events, corresponding to the introduction and increased frequency of the SARS-CoV-2 VOCs Gamma, Delta, and Omicron, respectively. This scenario is concerning during a pandemic since subsequent introductions of new lineages may contribute to the resurgence of cases and continuation of the disease, as reported for dengue and influenza 22 , 23 , 24 , 25 , 26 . We found that the three SARS-CoV-2 variant replacements in 2021 and early 2022 were linked to two waves of COVID-19, as observed in other studies at local and national levels 19 , 21 , 27 , 28 , 29 . The Gamma lineage emerged in late 2020 in Manaus, the capital of Amazonas state 6 , 30 , and it rapidly spread throughout Brazil, replacing Zeta and all other circulating SARS-CoV-2 variants to become the dominant lineage within six months (March–August 2021) 19 , 21 . Additionally, this VOC’s higher transmissibility rates and immune evasion led to reinfections and breakthrough infections 31 , 32 , 33 , 34 , 35 , 36 , 37 . The negative impact of Gamma across Brazil was amplified by the slow vaccination rate of early 2021, its greater severity of the disease, and elevated mortality risk in non-vaccinated patients, factors combined to overload health care systems and leading to a record number of deaths 19 , 29 . Our data also showed that the increased vaccination coverage from July 2021 helped decrease the number of COVID-19 cases and deaths in the RHD XV region as well as in other regions of Brazil. As a result, the spread of Delta was reduced, leading to a significant decrease in the number of cases and deaths at the national level. This finding becomes even more evident considering that previous infection with the Gamma variant itself did not confer a neutralizing antibody titer against the Delta variant as high as the one achieved by vaccination 38 . These observations contrasted with what was observed internationally, as the emergence of Delta triggered a new epidemic wave in several countries with varying degrees of vaccine coverage, such as India, Indonesia, Thailand, Myanmar, Nepal, several African nations, the United Kingdom, and Israel 39 , 40 , 41 , 42 , 43 , 44 , 45 . The most likely reason was the high vaccine coverage in the population when Delta was imported to Brazil, as shown in our study. Reinforcing these findings, our Reff analysis demonstrated that when Delta replaced Gamma in September 2021, there was a slight increase in the reproduction number for SARS-CoV-2, quickly followed by a decrease, but this did not impact the number of cases reported at the time, suggesting that higher immune protection of the population helped contain virus spread. Indeed, by the time Delta increased in frequency in the RHD XV, most of the population had been fully vaccinated with two doses of the inactivated-virus Sinovac/CoronaVac vaccines, and booster distribution had begun. Our study shows that these efforts effectively prevented severe cases and deaths. Moreover, these results are reinforced by studies demonstrating the effectiveness of the CoronaVac booster in inducing a potent immune response and elevated virus-specific antibody levels, increasing Delta variant neutralization activity, and subsequently preventing infection and severe outcomes 38 , 46 , 47 , 48 .

After the introduction and spread of Omicron, we observed a new resurgence of cases (January 2022); however, there was only a slight increase in the number of deaths in municipalities within the RHD XV region, corroborating the epidemiological landscape seen in Brazil as a whole. The Omicron variant was detected in South Africa and Botswana in November 2021, alongside an exponential rise in the incidence of COVID-19 8 . Phylogenetic analyses estimated that Omicron emerged in October 2021 with a significant R0, contributing to its vast and rapid spread. Indeed , our analyses showed a sharp peak in the Reff for SARS-CoV-2 (>2) when Omicron was introduced and increased in frequency, which was not observed when Gamma and Delta were the dominant variants, reinforcing the transmissibility of Omicron. The higher transmission rate of this variant is related to the constellation of mutations it displays: over 30 mutations in the spike glycoprotein, several in the receptor binding domain and N-terminal domain, which reduced its sensitivity to neutralization by anti-SARS-CoV-2 antibodies induced by previous infection or vaccination 8 . Despite Omicron’s pronounced transmissibility compared to Delta 49 and higher immune evasion compared to previous VOCs 50 , it exhibited reduced severity, leading to lower hospitalization rates 51 , 52 . Our results showed this same pattern; even though the number of cases rose abruptly from January 2022 in cities in the RHD XV region and throughout Brazil, the number of deaths was much lower than previously observed. The main factor underlying this pattern is likely attributed to the high rates of booster vaccination among the population, which is shown to promote higher titers of neutralizing antibodies 53 , 54 , 55 , 56 and strong protection against severe disease and death 57 .

Analyzing the spread of the different VOC in the RDH XV region and Brazil, our data showed that most of viral importation events to RHD XV region were from several states from Northeast region. Moreover, a more detailed analysis showed that the majority of the importations occurred in January 2021, a holiday and vacation periods in Brazil, in which a decrease in the social index isolation was observed in SJdRP 19 . Additionally, we observed lower virus exchange among the different Brazilian regions when Gamma was the dominant variant compared to Delta. One explanation is that by the time Gamma was circulating (March–August 2021), Brazil implemented more severe restrictions and social isolation, and vaccination was initiated 29 . However, when Delta replaced Gamma, the restriction measures had been loosened or abandoned, leading to higher virus exchange among the Brazilian states despite the lower numbers of notified COVID-19 cases. Nevertheless, an opposite pattern was observed in RHD XV since a more intense viral movement was reported when Gamma was the prevalent SARS-CoV-2 lineage. This likely resulted from the burst of COVID-19 cases reported from April 2021 that led to a record number of deaths and intensive care unit (ICU) occupancy rates. Because SJdRP has one of the most important centers for COVID-19 care and treatment, the city received people from various municipalities in the RHD XV, leading to higher rates of SARS-CoV-2 importation and exportation; still, when Delta was predominant, the population had been vaccinated full or partially that was fundamental for the decrease of transmission rates. Banho, Sacchetto, et al. 19 showed that ICU occupancy reached 100% in SJdRP when Gamma was prevalent in the RHD XV, suggesting that the intense virus importations and exportations observed in 2021 were related to SJRP’s role as the headquarters of RHD XV and home to the main hospital responsible for SARS-CoV-2 diagnosis, receiving over 5700 admissions up to June 2021 19 . During Delta circulation, the vaccine coverage was high, which helped to decrease the severity of the disease, probably leading to lower demand for treatment in more specialized healthcare centers such as HB, and consequently impacting virus circulation and transmission among the cities within the district.

Interestingly, while we expected Omicron to display the same pattern as Delta in Brazil, we observed significantly less virus exchange. This may be related to the sampling coverage nationwide, since from December 2021 to April 2022, only 933 full-coverage complete genomes of SARS-CoV-2 classified as Omicron were available at GISAID ( https://www.epicov.org/ ). The most Brazilian states from which Omicron genomes were retrieved showed poor sampling, which may have influenced the analysis and is a limitation of the study. Moreover, it is important to highlight that sampling representativeness differed for Gamma, Delta, and Omicron since SARS-CoV-2 genomes from 84, 41, and 28 RHD XV municipalities were sampled when these variants were circulating, respectively. This difference may limit the analysis of the spatiotemporal spread of SARS-CoV-2 whithin the RHD XV region. However, at the same time, it suggests that when infected people had milder symptoms (due to vaccine efficiency), fewer sought diagnoses in the health system, thus reducing the availability of collected samples for genomic surveillance.

Here we demonstrated that genomic surveillance of SARS-CoV-2 variants in SJdRP and neighboring cities can bring general insights about the national scenario of SARS-CoV-2 evolutionary course and transmission, mainly in midsize and major cities. However, it is important to highlight that this study has limitations, considering the spatiotemporal dynamic and virus importation and exportation events. This because, our data were based on SARS-CoV-2 genome sequences from capital and major cities of each state, meaning that, perhaps it does not reflect the pandemic progression in smaller cities of different Brazilian regions, that are located far away from larger and more populated municipalities, and which often have limited access to vaccination or other public health measures to contain the pandemic. Thus, additional analysis considering SARS-CoV-2 genomes from smaller cities of all Brazilian states are needed to reinforce our findings.

Therefore, using epidemiological data, genomic sequencing, and phylogeographic analyses, we demonstrated three well-defined clade replacement events in the RHD XV region, corresponding to the introduction and spread of the Gamma, Delta, and Omicron variants. The rapidly increasing prevalence of these VOCs triggered two COVID-19 epidemic waves, which were significantly influenced by the vaccination landscape. Our study revealed that the effectiveness of vaccination in mitigating new cases during Delta and Omicron circulation was six and eleven times higher, respectively, than during Gamma’s dominance. Additionally, vaccination coverage and booster doses were highly effective in reducing cases and deaths at local and national level. Thoroughly, our results revealed that SJdRP played a pivotal role in disseminating SARS-CoV-2 lineages to neighboring cities within the district. This underscores SJdRP’s suitability as a focal point for genomic surveillance, providing a reliable reflection of the national pattern of SARS-CoV-2 spread and evolution in midsize and major Brazilian cities.

Material and methods

Ethics statement.

This study was approved by the Ethics Committee of the São José do Rio Preto School of Medicine (FAMERP) (protocol number: CAAE #31588920.0.0000.5415, on November 29, 2021). Written informed consent was waived by the institutional review board (IRB) since all samples were collected for routine diagnosis, and the data were analyzed anonymously, ensuring total confidentiality for all participants.

Epidemiological data

Data from reported and confirmed COVID-19 cases in Brazil were provided by the Brazilian Ministry of Health and are available at https://github.com/wcota/covid19br 58 . To perform the analyses, we added the geographical locations according to Brazilian regions (North, Northeast, Southeast, South, Midwest, the Regional Health District XV (RHD XV) and São José do Rio Preto (SJdRP)). The effective reproduction number (Reff) for SARS-CoV-2 over the study period was estimated using the EpiEstim 59 in R version 4.3.1 60 . We fit the time-varying Reff, assuming a parametric serial interval with a mean of five days using a 21-day sliding window. The Reff reflects the behavior of an epidemic, and by definition is the average number of secondary infections caused by an infected person at a given time, where R  > 1 indicates a growing epidemic, while an R  < 1 indicates a decrease in transmission. Negative binomial regressions of new cases or deaths by day were run with a 10% increase in the percentage of the vaccinated population, adjusting for the number of new tests for that day. Vaccine effectiveness and 95% confidence intervals (CI) were estimated as 1-exp(coefficient)) or 1-exp(lower or upper CI).

Clinical samples and molecular investigation

To monitor the epidemiological profile and spatiotemporal dynamics of the SARS-CoV-2 variants that circulated during 2021–2022, convenience samples, collected from January 2021 to April 2022, presenting positive diagnoses for COVID-19 in residents of municipalities within the RHD XV were randomly selected by the SPNPAESV for whole-genome sequencing based on the cycle threshold value (≤30) and availability of epidemiological metadata such as date of sample collection and municipality of residence to perform phylogeographic analyses.

For COVID-19 diagnosis, viral RNA was extracted, from nasopharyngeal samples, using the Extracta kit fast DNA and RNA viral (MVXA-P096 FAST; Loccus, Brazil) according to the manufacturer’s instructions, utilizing an Extracta 96 DNA and RNA extractor and purifier (Loccus, Brazil). Reverse transcription followed by real-time polymerase chain reaction (RT-qPCR) was performed with the GeneFinder COVID-19 Plus RealAmp kit (OSANG Healthcare, Korea), targeting the RNA-dependent RNA polymerase (RdRp), envelope (E), and nucleocapsid (N) genes of the SARS-CoV-2 genome and the human RNAse P. The RT-qPCR was conducted in a QuantStudio 5 Real-Time PCR System (Thermo Fisher Scientific, USA), and the results were analyzed in QuantStudio 5 software v1.5.1 (Thermo Fisher Scientific, USA) interpreted as cycle threshold value (Ct) less or equal to 40 as positive.

Whole-genome sequencing, genome assembling and lineage assignment

Samples presenting Ct value less or equal to 30 were randomly selected for whole-genome sequencing. Whole-genome amplification, and library preparation were performed using Illumina CovidSeq Test (Illumina Inc, USA), according to the instructions provided. The quality and size of the libraries were checked by Agilent 4150 TapeStation (Agilent Technologies Inc, USA). Libraries were pooled in equimolar concentrations, and the sequencing was conducted in the Illumina MiSeq System (Illumina Inc, USA), using MiSeq Reagent Kit v2 (2 × 150 bp cycles) (Illumina Inc, USA). The quality of the raw sequencing data was checked using FastQC software v. 0.11.9 61 and trimmed with Trimmomatic v. 0.39 62 to filter low-quality reads, low-quality bases, and reads with at least 75 base pairs (bp). The cleaned paired-end reads were mapped against the Wuhan-Hu-1 reference genome (NC_045512.2) using BWA mem v. 0.7.17 software 63 and SAMtools v. 1.10 64 for read sorting and indexing. Next, Pilon software 65 was used to improve insertion and deletion detection. Finally, SAMtools v. 1.10 64 was used to access the position depths in the BAM alignment, and SAMtools mpileup and iVar v. 1.3.1 66 were used to generate the consensus genomes (nucleotide positions presenting read depth <10 were considered ‘N’). The generated genomes were subjected to the Pangolin COVID-19 Lineage Assigner Tool version v. 4.0.5 67 to confirm the variant classification.

Phylogenetic analysis

The datasets used for the phylogenetic analysis included Brazilian SARS-CoV-2 complete genome sequences of collected from January 2021 to April 2022 and the SARS-CoV-2 reference genome retrieved from the GISAID database 68 . For the Brazilian phylogeny, we used a total of 4520 whole genomes, and for the RHD XV tree, we used a total of 3293 whole-genome sequences obtained in this study (Supplementary Tables 1 and 2 ). All the Brazilian genomes used in this study were downloaded from the GISAID database 68 , based on the criteria high-coverage and metadata availability. Next, the sequences were selected according to the collection date (from January 2021 to April 2022) and the location (capital cities of each Brazilian state). Nucleotide sequences were aligned using MAFFT v. 7.271 69 . Time-scale phylogenetic trees using the maximum-likelihood (ML) method were reconstructed in IQ-TREE v. 2.0.3.7 70 , using the best-fit model of nucleotide substitution according to the Bayesian information criterion (BIC) inferred by the ModelFinder tool 71 . The reliability of branching patterns was tested using a combination of ultrafast bootstrap (UFBoot) and the SH-like approximate likelihood-ratio test (SH-aLRT) 72 . To investigate the temporal signal from the ML trees, we regressed root-to-tip genetic distances against sample collection dates using the TempEst tool v. 1.5.1 73 , considering correlation coefficient >0.4 to accept temporal structure 74 . Next, generated phylogenies were submitted to TreeTime v. 0.9.3 75 to convert the raw ML trees into time-scaled trees, considering a constant molecular rate of 8.0 × 10 −4 nucleotide substitutions per site per year, according to Giovanetti et al. 29 . Finally, we used the time-scaled tree topologies to infer the number of viral exchange events between the five Brazilian regions and the RHD XV as well as within the RHD XV using TreeTime mugration v. 0.9.3, and by mapping the locations to tips and internal nodes from the annotated tree topology we were able to estimate the number of transition events (virus importations and exportations) among regions/cities 75 .

Phylogeography analysis

To better understand the spatiotemporal history of SARS-CoV-2 spread and transmission within the RHD XV and between this district and other regions of Brazil, we investigated the main variants circulating in the region in 2021 and early 2022. To do so, we identified monophyletic clades in the time-scaled phylogenetic trees for the main VOC circulating in 2021 (Gamma, Delta, and Omicron) and randomly extracted sequences from all different clades in each monophyletic group using the Microreact web application 76 to infer continuous phylogeography histories using the Markov chain Monte Carlo (MCMC) method in BEAST v1.10.4 software 77 , as described by Giovanetti et al. 29 . As a result of this, for each lineage we reconstructed an ML tree and accessed the molecular clock signal using the root-to-tip regression method implemented in TempEst v. 1.5.3 73 and removed outliers that may violate the molecular clock assumption. Next, we down-sampled the lineages to <600 taxa per clade to infer the phylogeography history using BEAST v1.10.4 77 and employing HKY as the nucleotide substitution model, a strict molecular clock and Bayesian skyline model as the coalescent tree prior. We also utilized a flexible relaxed random walk diffusion model 78 , 79 with Cauchy distribution and jitter window site of 0.01 to model the phylogenetic diffusion and spread of each lineage among the Brazilian regions and within the RHD XV. The MCMC chains were run for 250 million interactions and sampled every 25,000 steps. Convergence was assessed in Tracer v. 1.7 80 , and maximum clade credibility trees were summarized using Treeannotator v. 1.6.1 after discarding the initial 10% of steps as burn-in. Finally, SERAPHIM 81 , a package in R software v. 4.2.3 60 , was used to extract and map the spatiotemporal information in the posterior trees.

Geoprocessing

Databases that included the number of COVID-19 cases per municipality and the number of SARS-CoV-2 genomes sequenced per city were created according to the location/municipality of origin and sample collection date. Maps were created using R software version 3.6.3 82 . The shapefiles used in this study are available at: https://www.ibge.gov.br/geociencias/organizacao-do-territorio/malhas-territoriais/15774-malhas.html 61 .

Data availability

All SARS-CoV-2 genomes generated and analyzed in this study are available in the EpiCoV database in GISAID 68 , and their respective access numbers are provided in the Supplementary Tables 1 and 2 .

Code availability

Code for analysis and figures is publicly available on ( https://github.com/cab1992/SARS-CoV-2_genomic_surveillance ).

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Acknowledgements

We thank all our colleagues at the Hospital de Base de São José do Rio Preto for the support they provided during sample collection. We also thank the Network for Pandemic Alert of Emerging SARS-CoV-2 Variants for their contributions in the sequencing effort and their commitment and work during the COVID-19 pandemic. We acknowledge the Multiuser Laboratory (LMU) at the São José do Rio Preto School of Medicine (FAMERP) for allowing us to use their equipment, as well as the Bioinformatics Laboratory at the Brazilian National Laboratory for Scientific Computing (LNCC) in Petrópolis, Brazil for technical assistance. This work received support from the Rede Corona-Ômica BR CTI/FINEP, which is part of Rede Vírus/MCTI (FINEP 01.20.0029.000462/20, CNPq 404096/2020-4); the FAPESP-COVID Program (Grant #2020/04836-0 to M.L.N.), FAPESP (grant #2022/03645-1 to M.L.N. and #2023/14670-0 to C.A.B.), and partly by the Centers for Research in Emerging Infectious Diseases (CREID), via the “Coordinating Research on Emerging Arboviral Threats Encompassing the Neotropics (CREATE-NEO)” grant 1U01AI151807 awarded to N.V. by the National Institutes of Health (NIH/USA). This study was also supported by the São Paulo Research Foundation (FAPESP) (Grant Numbers: 2020/10127-1 and 2021/11944-6 - CeVIVAS), the Butantan Foundation and in part through National Institutes of Health USA grant U01 AI151698 for the United World Arbovirus Research Network (UWARN). M.L.N., P.R., J.P.A.J. are CNPq Research Fellows. The funders had no role in the study design, collection, analyses, or interpretation of data, drafting of the manuscript, or the decision to publish the results. M.G. is founded by PON “Ricerca e Innovazione” 2014−2020 and by the CRP-ICGEB RESEARCH GRANT 2020 Project CRP/BRA20-03, Contract CRP/20/03.

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C.A.B., B.M.A., N.V., and M.L.N. conceived and designed the study. C.A.B., B.C.M, L.S., A.K.S.L., A.R.J.L., G.R., A.J.M., C.R.S.B., M.C.E., S.C.S., S.N.S., E.S.R., E.V.S., D.T.C., S.K., R.A.B., B.P., L.G.C., L.L.C., P.A.A, F.A.S.C, J.A.S.N., R.M.T.G., M.D.P., J.C.C.L., E.C.M., H.F., M.G., and L.C.J.A. collected samples, curated metadata, performed molecular screening and provided SARS-CoV-2 genomic data. B.M.A. performed statistical and epidemiological analyses. C.A.B. and M.C.P.P. performed geoprocessing analyses. C.A.B. and B.M.A. conducted data analyses and interpretation. C.A.B., B.M.A., N.V., M.L.N. wrote the first draft of the manuscript. C.A.B., B.M.A., L.S., G.R., C.R.S.B., M.C.E., H.F., S.N.S., M.G., F.R.S., N.V., M.L.N. edited and revised the manuscript. D.T.C., P.R., J.P.A.J., F.R.S., N.V., and M.L.N. provided the resources for the survey. All authors approvedthe final version of the manuscript.

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Banho, C.A., de Carvalho Marques, B., Sacchetto, L. et al. Dynamic clade transitions and the influence of vaccination on the spatiotemporal circulation of SARS-CoV-2 variants. npj Vaccines 9 , 145 (2024). https://doi.org/10.1038/s41541-024-00933-w

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DOI : https://doi.org/10.1038/s41541-024-00933-w

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Long COVID Basics

• Long COVID is a serious illness that can result in chronic conditions requiring comprehensive care.
• Long COVID can include a wide range of ongoing symptoms and conditions that can last weeks, months, or even years after COVID-19 illness.
• Anyone who had a SARS-CoV-2 infection, the virus that causes COVID-19, can experience Long COVID, including children.
• COVID-19 vaccination is the best available tool to prevent Long COVID.
• Living with Long COVID can be difficult and isolating, especially when there are no immediate answers or solutions.

About Long COVID

Long COVID is defined as a chronic condition that occurs after SARS-CoV-2 infection and is present for at least 3 months. Long COVID includes a wide range of symptoms or conditions that may improve, worsen, or be ongoing.

Anyone can get Long COVID‎

Most people with Long COVID experience symptoms days after first learning they had COVID-19, but some people who later develop Long COVID do not know when they were infected. People can be reinfected with SARS-CoV-2 multiple times. Each time a person is infected with SARS-CoV-2, they have a risk of developing Long COVID. Long COVID symptoms and conditions can emerge, persist, resolve, and reemerge over weeks and months. These symptoms and conditions can range from mild to severe, may require comprehensive care, and can even result in a disability .

While rates of new cases of Long COVID have decreased since the beginning of the COVID-19 pandemic, it remains a serious public health concern as millions of U.S. adults and children have been affected by Long COVID.

Who is at risk

While anyone who gets COVID-19 can develop Long COVID, studies have shown that some groups of people are more likely to develop Long COVID than others, including (not a comprehensive list):

• Hispanic and Latino people
• People who have experienced more severe COVID-19 illness, especially those who were hospitalized or needed intensive care
• People with underlying health conditions and adults who are 65 or older
• People who did not get a COVID-19 vaccine

Health inequities affect populations at risk for Long COVID

Health inequities from disability , economic, geographic, and other social factors disproportionately affect some groups of people. These inequities can increase the risk of negative health outcomes and impact from Long COVID.

CDC emphasizes core strategies to lower health risks from COVID-19, including severe outcomes such as hospitalization and death. Preventing severe outcomes from COVID-19 illness helps prevent Long COVID. Steps you can take to protect yourself and others include:

• Staying up to date on COVID-19 vaccination .
• Practicing good hygiene (practices like handwashing that improve cleanliness)
• Taking steps for cleaner air
• Use precautions to prevent spread
• Seek healthcare promptly for testing and/or treatment if you have risk factors for severe illness ; treatment may help lower your risk of severe illness

Vaccination can prevent Long COVID‎

Testing and diagnosis.

Long COVID is not one illness. There is no laboratory test that can determine if your symptoms or conditions are due to Long COVID. A positive SARS-CoV-2 test is not required for a Long COVID diagnosis. Your healthcare provider considers a diagnosis of Long COVID based on:

• Your health history
• If you had a diagnosis of COVID-19 by a positive test, symptoms, or exposure
• A health examination

Clinical evaluations and results of routine blood tests, chest X-rays, and electrocardiograms may be normal in someone with Long COVID. People experiencing Long COVID should seek care from a healthcare provider to create a personal medical management plan and improve their symptoms and quality of life. Talk to your healthcare provider if you think you or your child has Long COVID.

Similar conditions

Some people experiencing Long COVID symptoms have symptoms similar to those reported by people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and other poorly understood chronic illnesses that may occur after other infections. These unexplained symptoms or conditions may be misunderstood by healthcare providers, which can result in a delay in diagnosis and people receiving the appropriate care or treatment.

What CDC is doing

CDC is working with other federal agencies to better understand and address the long-term impacts of Long COVID , who gets Long COVID, and why. CDC supports these goals by:

• Partnering with state and local jurisdictions
• Supporting healthcare providers
• Promoting and conducting research

Studies are in progress to learn more about Long COVID and identify further measures to help prevent Long COVID. CDC and partners use multiple approaches to support and conduct research that estimates:

• How many people experience Long COVID and why
• Which groups of people are disproportionately impacted by Long COVID
• How new variants may affect Long COVID
• The role that COVID-19 vaccination plays in preventing Long COVID

Each approach helps CDC and its partners better understand Long COVID and how healthcare providers can treat or support patients living with these long-term effects. CDC posts data on Long COVID and provides analyses. The most recent CDC data and analyses on Long COVID can be found on the U.S. Census Bureau's Household Pulse Survey . CDC will continue to share information with healthcare providers to help them evaluate and manage these conditions.

• The Office of Long COVID Research and Practice (OLC) (HHS)
• Long COVID (Veterans Affairs)
• Coronavirus Resources (Department of Labor)
• RECOVER COVID Initiative

Long COVID reports

• Implementation of the Government-wide Response to Long COVID (HHS)
• National Research Action Plan (covid.gov)
• Services and Supports for Longer-Term Impacts of COVID-19
• Health+ Long Covid Human-Centered Design Report (HHS)
• Whole Health System Approach to Long COVID (Veterans Affairs)

COVID-19 (coronavirus disease 2019) is a disease caused by a virus named SARS-CoV-2. It can be very contagious and spreads quickly.

For Everyone

Health care providers, public health.

COVID-19: Long-term effects

Some people continue to experience health problems long after having COVID-19. Understand the possible symptoms and risk factors for post-COVID-19 syndrome.

Most people who get coronavirus disease 2019 (COVID-19) recover within a few weeks. But some people — even those who had mild versions of the disease — might have symptoms that last a long time afterward. These ongoing health problems are sometimes called post- COVID-19 syndrome, post- COVID conditions, long COVID-19 , long-haul COVID-19 , and post acute sequelae of SARS COV-2 infection (PASC).

What is post-COVID-19 syndrome and how common is it?

Post- COVID-19 syndrome involves a variety of new, returning or ongoing symptoms that people experience more than four weeks after getting COVID-19 . In some people, post- COVID-19 syndrome lasts months or years or causes disability.

Research suggests that between one month and one year after having COVID-19 , 1 in 5 people ages 18 to 64 has at least one medical condition that might be due to COVID-19 . Among people age 65 and older, 1 in 4 has at least one medical condition that might be due to COVID-19 .

What are the symptoms of post-COVID-19 syndrome?

The most commonly reported symptoms of post- COVID-19 syndrome include:

• Symptoms that get worse after physical or mental effort
• Lung (respiratory) symptoms, including difficulty breathing or shortness of breath and cough

Other possible symptoms include:

• Neurological symptoms or mental health conditions, including difficulty thinking or concentrating, headache, sleep problems, dizziness when you stand, pins-and-needles feeling, loss of smell or taste, and depression or anxiety
• Joint or muscle pain
• Heart symptoms or conditions, including chest pain and fast or pounding heartbeat
• Digestive symptoms, including diarrhea and stomach pain
• Blood clots and blood vessel (vascular) issues, including a blood clot that travels to the lungs from deep veins in the legs and blocks blood flow to the lungs (pulmonary embolism)
• Other symptoms, such as a rash and changes in the menstrual cycle

Keep in mind that it can be hard to tell if you are having symptoms due to COVID-19 or another cause, such as a preexisting medical condition.

It's also not clear if post- COVID-19 syndrome is new and unique to COVID-19 . Some symptoms are similar to those caused by chronic fatigue syndrome and other chronic illnesses that develop after infections. Chronic fatigue syndrome involves extreme fatigue that worsens with physical or mental activity, but doesn't improve with rest.

Why does COVID-19 cause ongoing health problems?

Organ damage could play a role. People who had severe illness with COVID-19 might experience organ damage affecting the heart, kidneys, skin and brain. Inflammation and problems with the immune system can also happen. It isn't clear how long these effects might last. The effects also could lead to the development of new conditions, such as diabetes or a heart or nervous system condition.

The experience of having severe COVID-19 might be another factor. People with severe symptoms of COVID-19 often need to be treated in a hospital intensive care unit. This can result in extreme weakness and post-traumatic stress disorder, a mental health condition triggered by a terrifying event.

What are the risk factors for post-COVID-19 syndrome?

You might be more likely to have post- COVID-19 syndrome if:

• You had severe illness with COVID-19 , especially if you were hospitalized or needed intensive care.
• You had certain medical conditions before getting the COVID-19 virus.
• You had a condition affecting your organs and tissues (multisystem inflammatory syndrome) while sick with COVID-19 or afterward.

Post- COVID-19 syndrome also appears to be more common in adults than in children and teens. However, anyone who gets COVID-19 can have long-term effects, including people with no symptoms or mild illness with COVID-19 .

What should you do if you have post-COVID-19 syndrome symptoms?

If you're having symptoms of post- COVID-19 syndrome, talk to your health care provider. To prepare for your appointment, write down:

• When your symptoms started
• What makes your symptoms worse
• How often you experience symptoms
• How your symptoms affect your activities

Your health care provider might do lab tests, such as a complete blood count or liver function test. You might have other tests or procedures, such as chest X-rays, based on your symptoms. The information you provide and any test results will help your health care provider come up with a treatment plan.

In addition, you might benefit from connecting with others in a support group and sharing resources.

• Long COVID or post-COVID conditions. Centers for Disease Control and Prevention. https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects.html. Accessed May 6, 2022.
• Post-COVID conditions: Overview for healthcare providers. Centers for Disease Control and Prevention. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/post-covid-conditions.html. Accessed May 6, 2022.
• Mikkelsen ME, et al. COVID-19: Evaluation and management of adults following acute viral illness. https://www.uptodate.com/contents/search. Accessed May 6, 2022.
• Saeed S, et al. Coronavirus disease 2019 and cardiovascular complications: Focused clinical review. Journal of Hypertension. 2021; doi:10.1097/HJH.0000000000002819.
• AskMayoExpert. Post-COVID-19 syndrome. Mayo Clinic; 2022.
• Multisystem inflammatory syndrome (MIS). Centers for Disease Control and Prevention. https://www.cdc.gov/mis/index.html. Accessed May 24, 2022.
• Patient tips: Healthcare provider appointments for post-COVID conditions. https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects/post-covid-appointment/index.html. Accessed May 24, 2022.
• Bull-Otterson L, et al. Post-COVID conditions among adult COVID-19 survivors aged 18-64 and ≥ 65 years — United States, March 2020 — November 2021. MMWR Morbidity and Mortality Weekly Report. 2022; doi:10.15585/mmwr.mm7121e1.

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