simple presentation about covid 19

• Patient Care & Health Information
• Diseases & Conditions
• Coronavirus disease 2019 (COVID-19)

COVID-19, also called coronavirus disease 2019, is an illness caused by a virus. The virus is called severe acute respiratory syndrome coronavirus 2, or more commonly, SARS-CoV-2. It started spreading at the end of 2019 and became a pandemic disease in 2020.

• Coronavirus

Coronaviruses are a family of viruses. These viruses cause illnesses such as the common cold, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and coronavirus disease 2019 (COVID-19).

The virus that causes COVID-19 spreads most commonly through the air in tiny droplets of fluid between people in close contact. Many people with COVID-19 have no symptoms or mild illness. But for older adults and people with certain medical conditions, COVID-19 can lead to the need for care in the hospital or death.

Staying up to date on your COVID-19 vaccine helps prevent serious illness, the need for hospital care due to COVID-19 and death from COVID-19 . Other ways that may help prevent the spread of this coronavirus includes good indoor air flow, physical distancing, wearing a mask in the right setting and good hygiene.

Medicine can limit the seriousness of the viral infection. Most people recover without long-term effects, but some people have symptoms that continue for months.

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Typical COVID-19 symptoms often show up 2 to 14 days after contact with the virus.

Symptoms can include:

• Shortness of breath.
• Loss of taste or smell.
• Extreme tiredness, called fatigue.
• Digestive symptoms such as upset stomach, vomiting or loose stools, called diarrhea.
• Pain, such as headaches and body or muscle aches.
• Fever or chills.
• Cold-like symptoms such as congestion, runny nose or sore throat.

People may only have a few symptoms or none. People who have no symptoms but test positive for COVID-19 are called asymptomatic. For example, many children who test positive don't have symptoms of COVID-19 illness. People who go on to have symptoms are considered presymptomatic. Both groups can still spread COVID-19 to others.

Some people may have symptoms that get worse about 7 to 14 days after symptoms start.

Most people with COVID-19 have mild to moderate symptoms. But COVID-19 can cause serious medical complications and lead to death. Older adults or people who already have medical conditions are at greater risk of serious illness.

COVID-19 may be a mild, moderate, severe or critical illness.

• In broad terms, mild COVID-19 doesn't affect the ability of the lungs to get oxygen to the body.
• In moderate COVID-19 illness, the lungs also work properly but there are signs that the infection is deep in the lungs.
• Severe COVID-19 means that the lungs don't work correctly, and the person needs oxygen and other medical help in the hospital.
• Critical COVID-19 illness means the lung and breathing system, called the respiratory system, has failed and there is damage throughout the body.

Rarely, people who catch the coronavirus can develop a group of symptoms linked to inflamed organs or tissues. The illness is called multisystem inflammatory syndrome. When children have this illness, it is called multisystem inflammatory syndrome in children, shortened to MIS -C. In adults, the name is MIS -A.

When to see a doctor

Contact a healthcare professional if you test positive for COVID-19 . If you have symptoms and need to test for COVID-19 , or you've been exposed to someone with COVID-19 , a healthcare professional can help.

People who are at high risk of serious illness may get medicine to block the spread of the COVID-19 virus in the body. Or your healthcare team may plan regular checks to monitor your health.

Get emergency help right away for any of these symptoms:

• Can't catch your breath or have problems breathing.
• Skin, lips or nail beds that are pale, gray or blue.
• New confusion.
• Trouble staying awake or waking up.
• Chest pain or pressure that is constant.

This list doesn't include every emergency symptom. If you or a person you're taking care of has symptoms that worry you, get help. Let the healthcare team know about a positive test for COVID-19 or symptoms of the illness.

More Information

• COVID-19 vs. flu: Similarities and differences
• COVID-19, cold, allergies and the flu
• Unusual symptoms of coronavirus

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COVID-19 is caused by infection with the severe acute respiratory syndrome coronavirus 2, also called SARS-CoV-2.

The coronavirus spreads mainly from person to person, even from someone who is infected but has no symptoms. When people with COVID-19 cough, sneeze, breathe, sing or talk, their breath may be infected with the COVID-19 virus.

The coronavirus carried by a person's breath can land directly on the face of a nearby person, after a sneeze or cough, for example. The droplets or particles the infected person breathes out could possibly be breathed in by other people if they are close together or in areas with low air flow. And a person may touch a surface that has respiratory droplets and then touch their face with hands that have the coronavirus on them.

It's possible to get COVID-19 more than once.

• Over time, the body's defense against the COVID-19 virus can fade.
• A person may be exposed to so much of the virus that it breaks through their immune defense.
• As a virus infects a group of people, the virus copies itself. During this process, the genetic code can randomly change in each copy. The changes are called mutations. If the coronavirus that causes COVID-19 changes in ways that make previous infections or vaccination less effective at preventing infection, people can get sick again.

The virus that causes COVID-19 can infect some pets. Cats, dogs, hamsters and ferrets have caught this coronavirus and had symptoms. It's rare for a person to get COVID-19 from a pet.

Risk factors

The main risk factors for COVID-19 are:

• If someone you live with has COVID-19 .
• If you spend time in places with poor air flow and a higher number of people when the virus is spreading.
• If you spend more than 30 minutes in close contact with someone who has COVID-19 .

Many factors affect your risk of catching the virus that causes COVID-19 . How long you are in contact, if the space has good air flow and your activities all affect the risk. Also, if you or others wear masks, if someone has COVID-19 symptoms and how close you are affects your risk. Close contact includes sitting and talking next to one another, for example, or sharing a car or bedroom.

It seems to be rare for people to catch the virus that causes COVID-19 from an infected surface. While the virus is shed in waste, called stool, COVID-19 infection from places such as a public bathroom is not common.

Serious COVID-19 illness risk factors

Some people are at a higher risk of serious COVID-19 illness than others. This includes people age 65 and older as well as babies younger than 6 months. Those age groups have the highest risk of needing hospital care for COVID-19 .

Not every risk factor for serious COVID-19 illness is known. People of all ages who have no other medical issues have needed hospital care for COVID-19 .

Known risk factors for serious illness include people who have not gotten a COVID-19 vaccine. Serious illness also is a higher risk for people who have:

• Sickle cell disease or thalassemia.
• Serious heart diseases and possibly high blood pressure.
• Chronic kidney, liver or lung diseases.

People with dementia or Alzheimer's also are at higher risk, as are people with brain and nervous system conditions such as stroke. Smoking increases the risk of serious COVID-19 illness. And people with a body mass index in the overweight category or obese category may have a higher risk as well.

Other medical conditions that may raise the risk of serious illness from COVID-19 include:

• Cancer or a history of cancer.
• Type 1 or type 2 diabetes.
• Weakened immune system from solid organ transplants or bone marrow transplants, some medicines, or HIV .

This list is not complete. Factors linked to a health issue may raise the risk of serious COVID-19 illness too. Examples are a medical condition where people live in a group home, or lack of access to medical care. Also, people with more than one health issue, or people of older age who also have health issues have a higher chance of severe illness.

Related information

• COVID-19: Who's at higher risk of serious symptoms? - Related information COVID-19: Who's at higher risk of serious symptoms?

Complications

Complications of COVID-19 include long-term loss of taste and smell, skin rashes, and sores. The illness can cause trouble breathing or pneumonia. Medical issues a person already manages may get worse.

Complications of severe COVID-19 illness can include:

• Acute respiratory distress syndrome, when the body's organs do not get enough oxygen.
• Shock caused by the infection or heart problems.
• Overreaction of the immune system, called the inflammatory response.
• Blood clots.
• Kidney injury.

Post-COVID-19 syndrome

After a COVID-19 infection, some people report that symptoms continue for months, or they develop new symptoms. This syndrome has often been called long COVID, or post- COVID-19 . You might hear it called long haul COVID-19 , post-COVID conditions or PASC. That's short for post-acute sequelae of SARS -CoV-2.

Other infections, such as the flu and polio, can lead to long-term illness. But the virus that causes COVID-19 has only been studied since it began to spread in 2019. So, research into the specific effects of long-term COVID-19 symptoms continues.

Researchers do think that post- COVID-19 syndrome can happen after an illness of any severity.

Getting a COVID-19 vaccine may help prevent post- COVID-19 syndrome.

• Long-term effects of COVID-19

The Centers for Disease Control and Prevention (CDC) recommends a COVID-19 vaccine for everyone age 6 months and older. The COVID-19 vaccine can lower the risk of death or serious illness caused by COVID-19.

The COVID-19 vaccines available in the United States are:

2023-2024 Pfizer-BioNTech COVID-19 vaccine. This vaccine is available for people age 6 months and older.

Among people with a typical immune system:

• Children age 6 months up to age 4 years are up to date after three doses of a Pfizer-BioNTech COVID-19 vaccine.
• People age 5 and older are up to date after one Pfizer-BioNTech COVID-19 vaccine.
• For people who have not had a 2023-2024 COVID-19 vaccination, the CDC recommends getting an additional shot of that updated vaccine.

2023-2024 Moderna COVID-19 vaccine. This vaccine is available for people age 6 months and older.

• Children ages 6 months up to age 4 are up to date if they've had two doses of a Moderna COVID-19 vaccine.
• People age 5 and older are up to date with one Moderna COVID-19 vaccine.

2023-2024 Novavax COVID-19 vaccine. This vaccine is available for people age 12 years and older.

• People age 12 years and older are up to date if they've had two doses of a Novavax COVID-19 vaccine.

In general, people age 5 and older with typical immune systems can get any vaccine approved or authorized for their age. They usually don't need to get the same vaccine each time.

Some people should get all their vaccine doses from the same vaccine maker, including:

• Children ages 6 months to 4 years.
• People age 5 years and older with weakened immune systems.
• People age 12 and older who have had one shot of the Novavax vaccine should get the second Novavax shot in the two-dose series.

Talk to your healthcare professional if you have any questions about the vaccines for you or your child. Your healthcare team can help you if:

• The vaccine you or your child got earlier isn't available.
• You don't know which vaccine you or your child received.
• You or your child started a vaccine series but couldn't finish it due to side effects.

People with weakened immune systems

Your healthcare team may suggest added doses of COVID-19 vaccine if you have a moderately or seriously weakened immune system. The FDA has also authorized the monoclonal antibody pemivibart (Pemgarda) to prevent COVID-19 in some people with weakened immune systems.

Control the spread of infection

In addition to vaccination, there are other ways to stop the spread of the virus that causes COVID-19 .

If you are at a higher risk of serious illness, talk to your healthcare professional about how best to protect yourself. Know what to do if you get sick so you can quickly start treatment.

If you feel ill or have COVID-19 , stay home and away from others, including pets, if possible. Avoid sharing household items such as dishes or towels if you're sick.

In general, make it a habit to:

• Test for COVID-19 . If you have symptoms of COVID-19 test for the infection. Or test five days after you came in contact with the virus.
• Help from afar. Avoid close contact with anyone who is sick or has symptoms, if possible.
• Wash your hands. Wash your hands well and often with soap and water for at least 20 seconds. Or use an alcohol-based hand sanitizer with at least 60% alcohol.
• Cover your coughs and sneezes. Cough or sneeze into a tissue or your elbow. Then wash your hands.
• Clean and disinfect high-touch surfaces. For example, clean doorknobs, light switches, electronics and counters regularly.

Try to spread out in crowded public areas, especially in places with poor airflow. This is important if you have a higher risk of serious illness.

The CDC recommends that people wear a mask in indoor public spaces if you're in an area with a high number of people with COVID-19 in the hospital. They suggest wearing the most protective mask possible that you'll wear regularly, that fits well and is comfortable.

• COVID-19 vaccines: Get the facts - Related information COVID-19 vaccines: Get the facts
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Travel and COVID-19

Travel brings people together from areas where illnesses may be at higher levels. Masks can help slow the spread of respiratory diseases in general, including COVID-19 . Masks help the most in places with low air flow and where you are in close contact with other people. Also, masks can help if the places you travel to or through have a high level of illness.

Masking is especially important if you or a companion have a high risk of serious illness from COVID-19 .

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• Goldman L, et al., eds. COVID-19: Epidemiology, clinical manifestations, diagnosis, community prevention, and prognosis. In: Goldman-Cecil Medicine. 27th ed. Elsevier; 2024. https://www.clinicalkey.com. Accessed Dec. 17, 2023.
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• How to protect yourself and others. Centers for Disease Control and Prevention. https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/prevention.html. Accessed Jan. 10, 2024.
• People who are immunocompromised. Centers for Disease Control and Prevention. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-who-are-immunocompromised.html. Accessed Jan. 10, 2024.
• Masking during travel. Centers for Disease Control and Prevention. https://wwwnc.cdc.gov/travel/page/masks. Accessed Jan. 10, 2024.
• AskMayoExpert. COVID-19: Testing. Mayo Clinic. 2023.
• COVID-19 test basics. U.S. Food and Drug Administration. https://www.fda.gov/consumers/consumer-updates/covid-19-test-basics. Accessed Jan. 11, 2024.
• At-home COVID-19 antigen tests — Take steps to reduce your risk of false negative results: FDA safety communication. U.S. Food and Drug Administration. https://www.fda.gov/medical-devices/safety-communications/home-covid-19-antigen-tests-take-steps-reduce-your-risk-false-negative-results-fda-safety. Accessed Jan. 11, 2024.
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Coronaviruses are a large family of viruses that are known to cause illness ranging from the common cold to more severe diseases such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS).

A novel coronavirus (COVID-19) was identified in 2019 in Wuhan, China. This is a new coronavirus that has not been previously identified in humans.

This course provides a general introduction to COVID-19 and emerging respiratory viruses and is intended for public health professionals, incident managers and personnel working for the United Nations, international organizations and NGOs.

As the official disease name was established after material creation, any mention of nCoV refers to COVID-19, the infectious disease caused by the most recently discovered coronavirus.

Please note that the content of this course is currently being revised to reflect the most recent guidance. You can find updated information on certain COVID-19-related topics in the following courses: Vaccination: COVID-19 vaccines channel IPC measures: IPC for COVID-19 Antigen rapid diagnostic testing: 1) SARS-CoV-2 antigen rapid diagnostic testing ; 2) Key considerations for SARS-CoV-2 antigen RDT implementation

Please note: These materials were last updated on 16/12/2020.

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Last Update: August 18, 2023 .

• Continuing Education Activity

Coronavirus disease 2019 (COVID-19) is a highly contagious infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has had a catastrophic effect on the world, resulting in more than 6 million deaths worldwide. It has emerged as the most consequential global health crisis since the era of the influenza pandemic of 1918. As the virus mutates, treatment guidelines are altered to reflect the most efficacious therapies. This activity is a comprehensive review of the disease presentation, complications, and current guideline-recommended treatment options for managing this disease.

• Screen individuals based on exposure and symptom criteria to identify potential COVID-19 cases.
• Identify the clinical features and radiological findings expected in patients with COVID-19.
• Apply the recommended treatment options for patients with COVID-19.
• Create strategies with the interprofessional team for improving care coordination to care for patients with COVID-19 to help improve clinical outcomes.
• Introduction

Coronavirus disease 2019 (COVID-19) is a highly contagious viral illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has had a catastrophic effect on the world, resulting in more than 6 million deaths worldwide. After the first cases of this predominantly respiratory viral illness were reported in Wuhan, Hubei Province, China, in late December 2019, SARS-CoV-2 rapidly disseminated worldwide. This compelled the World Health Organization (WHO) to declare it a global pandemic on March 11, 2020. [1]

Even though substantial progress in clinical research has led to a better understanding of SARS-CoV-2, many countries continue to have outbreaks of this viral illness. These outbreaks are primarily attributed to the emergence of mutant variants of the virus. Like other RNA viruses, SARS-CoV-2 adapts with genetic evolution and developing mutations. This results in mutant variants that may have different characteristics than their ancestral strains. Several variants of SARS-CoV-2 have been described during the course of this pandemic, among which only a few are considered variants of concern (VOCs). Based on the epidemiological update by the WHO, 5 SARS-CoV-2 VOCs have been identified since the beginning of the pandemic:

• Alpha (B.1.1.7): First variant of concern, which was described in the United Kingdom (UK) in late December 2020 [2]
• Beta (B.1.351) : First reported in South Africa in December 2020 [2]
• Gamma (P.1) : First reported in Brazil in early January 2021 [2]
• Delta (B.1.617.2):  First reported in India in December 2020 [2]
• Omicron   (B.1.1.529): First reported in South Africa in November 2021 [3]

Despite the unprecedented speed of vaccine development against the prevention of COVID-19 and robust global mass vaccination efforts, the emergence of new SARS-CoV-2 variants threatens to overturn the progress made in limiting the spread of this disease. This review aims to comprehensively describe the etiology, epidemiology, pathophysiology, and clinical features of COVID-19. This review also provides an overview of the different variants of SARS-CoV-2 and the guideline-recommended treatment (as of January 2023) for managing this disease. 

Coronaviruses (CoVs) are positive-sense single-stranded RNA (+ssRNA) viruses with a crown-like appearance under an electron microscope ( coronam  is the Latin term for crown) due to the presence of spike glycoproteins on the envelope. [1] The subfamily  Orthocoronavirinae  of the  Coronaviridae  family (order  Nidovirales ) classifies into 4 genera of CoVs: 

• Alphacoronavirus (alphaCoV)
• Betacoronavirus (betaCoV)
• Deltacoronavirus (deltaCoV)
• Gammacoronavirus (gammaCoV)

BetaCoV genus is further divided into 5 sub-genera or lineages. [4]  Genomic characterization has shown that bats and rodents are the probable gene sources of alphaCoVs and betaCoVs. Avian species seem to be the source of deltaCoVs and gammaCoVs. CoVs have become significant pathogens of emerging respiratory disease outbreaks. Members of this large family of viruses can cause respiratory, enteric, hepatic, and neurological diseases in different animal species, including camels, cattle, cats, and bats.

These viruses can cross species barriers and infect humans as well. Seven human CoVs (HCoVs) capable of infecting humans have been identified. Some HCoVs were identified in the mid-1960s, while others were only detected in the new millennium. In general, estimates suggest that 2% of the population are healthy carriers of CoVs and that these viruses are responsible for about 5% to 10% of acute respiratory infections. [5]  

• Common human CoVs : HCoV-OC43 and HCoV-HKU1 (betaCoVs of the A lineage), HCoV-229E, and HCoV-NL63 (alphaCoVs). These viruses can cause common colds and self-limiting upper respiratory tract infections in immunocompetent individuals. However, in immunocompromised and older patients, lower respiratory tract infections can occur due to these viruses.
• Other human CoVs : SARS-CoV and MERS-CoV (betaCoVs of the B and C lineage, respectively). These viruses are considered more virulent and capable of causing epidemics with respiratory and extra-respiratory manifestations of variable clinical severity. [1]  

SARS-CoV-2 is a novel betaCoV belonging to the same subgenus as the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which have been previously implicated in SARS-CoV and MERS-CoV epidemics with mortality rates up to 10% and 35%, respectively. [6]  It has a round or elliptic and often pleomorphic form and a diameter of approximately 60 to 140 nm. Like other CoVs, it is sensitive to ultraviolet rays and heat. [6]  

The inactivation temperature of SARS-CoV-2 is being researched. A stainless steel surface held at an air temperature of 54.5°C (130 °F) results in the inactivation of 90% of SARS-CoV-2 in approximately 36 minutes. [7]  It resists lower temperatures, even those below 0°C. However, lipid solvents can effectively inactivate these viruses, including ether (75%), ethanol, chlorine-containing disinfectant, peroxyacetic acid, and chloroform (except for chlorhexidine).

Although the origin of SARS-CoV-2 is currently unknown, it is widely postulated to have a zoonotic transmission. [1]  Genomic analyses suggest that SARS-CoV-2 probably evolved from a strain found in bats. The genomic comparison between the human SARS-CoV-2 sequence and known animal coronaviruses revealed high homology (96%) between the SARS-CoV-2 and the betaCoV RaTG13 of bats ( Rhinolophus affinis ). [8]  Similar to SARS and MERS, it has been hypothesized that SARS-CoV-2 advanced from bats to intermediate hosts, such as pangolins and minks, and then to humans. [9] [10]

SARS-CoV-2 Variants

A globally dominant D614G variant was eventually identified and associated with increased transmissibility but without the ability to cause severe illness. [11] Another variant was attributed to transmission from infected farmed mink in Denmark but was not associated with increased transmissibility. [10]  Since then, multiple variants of SARS-CoV-2 have been described, of which a few are considered variants of concern (VOCs) due to their potential to cause enhanced transmissibility or virulence. The United States Centers for Disease Control and Prevention (CDC) and the WHO have independently established a classification system for distinguishing the emerging variants of SARS-CoV-2 into variants of concern(VOCs) and variants of interest(VOIs).

SARS-CoV-2 Variants of Concern (VOCs)

• Alpha (B.1.1.7 lineage)
• In late December 2020, the Alpha variant,   or GRY  (formerly GR/501Y.V1), was reported in the UK based on whole-genome sequencing of samples from patients who tested positive for SARS-CoV-2. [12] [13]
• The variant   was also identified using a commercial assay characterized by the absence of the S gene (S-gene target failure, SGTF) in PCR samples. The B.1.1.7 variant includes 17 mutations in the viral genome. Of these, 8 mutations (Δ69-70 deletion, Δ144 deletion, N501Y, A570D, P681H, T716I, S982A, D1118H) are in the spike (S) protein. N501Y shows an increased affinity of the spike protein to ACE 2 receptors, enhancing the viral attachment and subsequent entry into host cells. [14] [15] [16]
• This alpha variant was reportedly 43% to 82% more transmissible, surpassing preexisting variants of SARS-CoV-2 to emerge as the dominant SARS-CoV-2 variant in the UK. [15]  
• An initial matched case-control study reported no significant difference in the risk of hospitalization or associated mortality with the B.1.1.7 lineage variant compared to other existing variants. However, subsequent studies have reported that people infected with B.1.1.7 lineage variant had increased disease severity compared to those infected with other circulating variants. [17] [13]  
• A large matched cohort study in the UK reported that the mortality hazard ratio of patients infected with the B.1.1.7 lineage variant was 1.64 (95% confidence interval 1.32 to 2.04, P<0.0001) compared to patients with previously circulating strains. [18]
• Another study reported that the B 1.1.7 variant was associated with increased mortality compared to other SARS-CoV-2 variants (HR= 1.61, 95% CI 1.42-1.82). [19]  The risk of death was reportedly greater (adjusted hazard ratio 1.67, 95% CI 1.34-2.09) among individuals with confirmed B.1.1.7 infection compared to individuals with non-B.1.1.7 SARS-CoV-2. [20]
• Beta (B.1.351 lineage)
• The Beta variant, or GH501Y.V2 with multiple spike mutations, resulted in the second wave of COVID-19 infections and was first detected in South Africa in October 2020. [21]
• The B.1.351 variant includes 9 mutations (L18F, D80A, D215G, R246I, K417N, E484K, N501Y, D614G, and A701V) in the spike protein, of which 3 mutations (K417N, E484K, and N501Y) are located in the receptor binding domain (RBD) and increase its binding affinity for the ACE receptors. [22] [14] [23]  
• SARS-CoV-2 501Y.V2 (B.1.351 lineage) was reported in the US at the end of January 2021.
• This variant had an increased risk of transmission and reduced neutralization by monoclonal antibody therapy, convalescent sera, and post-vaccination sera. [24]
• Gamma (P.1 lineage)
• The Gamma variant, or  GR/501Y.V3 , was identified in December 2020 in Brazil and was first detected in the US in January 2021. [25]  
• This B.1.1.28 variant harbors ten mutations in the spike protein (L18F, T20N, P26S, D138Y, R190S, H655Y, T1027I V1176, K417T, E484K, and N501Y). Three mutations (L18F, K417N, E484K) are located in the RBD, similar to the B.1.351 variant. [25]
• The Delta variant was initially identified in December 2020 in India and was responsible for the deadly second wave of COVID-19 infections in April 2021 in India. In the United States, this variant was first detected in March 2021. [2]
• The B.1.617.2 variant harbors ten mutations ( T19R, (G142D*), 156del, 157del, R158G, L452R, T478K, D614G, P681R, D950N) in the spike protein.
• The Omicron variant was first identified in South Africa on 23 November 2021 after an uptick in the number of cases of COVID-19. [26]  
• Omicron was quickly recognized as a VOC due to more than 30 changes to the spike protein of the virus and the sharp rise in the number of cases observed in South Africa. [27]  The reported mutations include T91 in the envelope, P13L, E31del, R32del, S33del, R203K, G204R in the nucleocapsid protein, D3G, Q19E, A63T in the matrix, N211del/L212I, Y145del, Y144del, Y143del, G142D, T95I, V70del, H69del, A67V in the N-terminal domain of the spike, Y505H, N501Y, Q498R, G496S, Q493R, E484A, T478K, S477N, G446S, N440K, K417N, S375F, S373P, S371L, G339D in the receptor-binding domain of the spike, D796Y in the fusion peptide of the spike, L981F, N969K, Q954H in the heptad repeat 1 of the spike as well as multiple other mutations in the non-structural proteins and spike protein. [28]
• Many subvariants of Omicron, such as BA.1, BA.2, BA.3, BA.4, and BA.5, have been identified. [3]

Transmission of SARS-CoV-2

• The primary mode of transmission of SARS-CoV-2 is via exposure to respiratory droplets carrying the infectious virus from close contact or direct transmission from presymptomatic, asymptomatic, or symptomatic individuals harboring the virus. [1]
• Airborne transmission with aerosol-generating procedures has also been implicated in the spread of COVID-19. Data implicating airborne transmission of SARS-CoV-2 in the absence of aerosol-generating procedures is present; however, this mode of transmission has not been universally acknowledged.
• Fomite transmission from contamination of inanimate surfaces with SARS-CoV-2 has been well characterized based on many studies reporting the viability of SARS-CoV-2 on various porous and nonporous surfaces. Under experimental conditions, SARS-CoV-2 was stable on stainless steel and plastic surfaces compared to copper and cardboard surfaces, with the viable virus being detected up to 72 hours after inoculating the surfaces with the virus. [29]  The viable virus was isolated for up to 28 days at 20°C from nonporous surfaces such as glass and stainless steel. Conversely, recovery of SARS-CoV-2 on porous materials was reduced compared with nonporous surfaces. [30]  In hospital settings, the SARS-CoV-2 has been detected on floors, computer mice, trash cans, sickbed handrails, and in the air (up to 4 meters from patients). [31]  The Centers for Disease Control and Prevention (CDC) has stated that individuals can be infected with SARS-CoV-2 via contact with surfaces contaminated by the virus, but the risk is low and is not the main route of transmission of this virus.
• Epidemiologic data from several case studies have reported that patients with SARS-CoV-2 infection have the live virus in feces implying possible fecal-oral transmission. [32]
• A meta-analysis that included 936 neonates from mothers with COVID-19 showed vertical transmission is possible but occurs in a minority of cases. [33]
• Epidemiology

COVID-19 was the third leading cause of death in the United States (USA) in 2020 after heart disease and cancer, with approximately 375,000 deaths. [34]  

Individuals of all ages are at risk of contracting this infection. However, patients aged ≥60 and patients with underlying medical comorbidities (obesity, cardiovascular disease, chronic kidney disease, diabetes, chronic lung disease, smoking, cancer, solid organ or hematopoietic stem cell transplant patients) have an increased risk of developing severe COVID-19 infection.

According to the CDC, age remains the strongest predictor of poor outcomes and severe illness in patients with COVID-19. Data from the National Vital Statistics System (NVSS) at CDC states that patients with COVID-19 aged 50 to 64 years have a 25 times higher risk of death when compared to adults infected with this illness and aged less than 30 years. In patients 65 to 74 years old, this risk increases to 60 times. In patients older than 85, the risk of death increases to 340 times. According to the CDC, these data include all deaths in the United States throughout the pandemic, from February 2020 to July 1, 2022, including deaths among unvaccinated individuals.

The percentage of COVID-19 patients requiring hospitalization was 6 times higher in those with preexisting medical conditions than those without medical conditions (45.4% vs. 7.6%) based on an analysis by Stokes et al. of confirmed cases reported to the CDC from January 22 to May 30, 2020. [35]  The study also reported that the percentage of patients who succumbed to this illness was 12 times higher in those with preexisting medical conditions than those without (19.5% vs 1.6%). [35]  

Data regarding the gender-based differences in COVID-19 suggests that male patients have a higher risk of severe illness and increased mortality due to COVID-19 compared to female patients. [36] [37]  Results from a retrospective cohort study from March 1 to November 21, 2020, evaluating the mortality rate in 209 United States of America (USA) acute care hospitals that included 42604 patients with confirmed SARS-CoV-2 infection, reported a higher mortality rate in male patients (12.5%) compared to female patients (9.6%). [38]

Racial and ethnic minority groups have been reported to have a higher percentage of COVID-19-related hospitalizations than White patients based on a recent CDC analysis of hospitalizations from an extensive administrative database that included approximately 300,000 COVID-19 patients hospitalized from March 2020 to December 2020. This high percentage of COVID-19-related hospitalizations among racial and ethnic groups was driven by a higher risk of exposure to SARS-CoV-2 and an increased risk of developing severe COVID-19 disease. [39]   A meta-analysis of 50 studies from USA and UK researchers noted that people of Black, Hispanic, and Asian ethnic minority groups are at increased risk of contracting and dying from COVID-19 infection. [40]  

COVID-19-related death rates were the highest among Hispanic persons. [34]  Another analysis by the CDC evaluating the risk of COVID-19 among sexual minority adults reported that underlying medical comorbidities which increase the risk of developing severe COVID-19 were more prevalent in sexual minority individuals than heterosexual individuals within the general population and within specific racial/ethnic groups. [41]

• Pathophysiology

Structurally and phylogenetically, SARS-CoV-2 is similar to SARS-CoV and MERS-CoV and is composed of 4 main structural proteins: spike (S), envelope (E) glycoprotein, nucleocapsid (N), and membrane (M) protein. It also contains 16 nonstructural proteins and 5-8 accessory proteins. [42]  

The surface spike (S) glycoprotein, which resembles a crown, is located on the outer surface of the virion. It undergoes cleavage into an amino (N)-terminal S1 subunit, which facilitates the incorporation of the virus into the host cell. The carboxyl (C)-terminal S2 subunit contains a fusion peptide, a transmembrane domain, and a cytoplasmic domain responsible for virus-cell membrane fusion. [43] [44]  The S1 subunit is further divided into a receptor-binding domain (RBD) and an N-terminal domain (NTD), which facilitates viral entry into the host cell and serves as a potential target for neutralization in response to antisera or vaccines . [45]  

The RBD is a fundamental peptide in the pathogenesis of infection as it represents a binding site for the human angiotensin-converting enzyme 2 (ACE2) receptors. Inhibition of the renin-angiotensin-aldosterone system (RAAS) does not increase the risk of hospitalization for COVID-19 and severe disease. [46]

SARS-CoV-2 gains entry into the host cells by binding the SARS-CoV-2 spike or S protein (S1) to the ACE2 receptors in the respiratory epithelium. ACE2 receptors are also expressed by other organs such as the upper esophagus, enterocytes from the ileum, myocardial cells, proximal tubular cells of the kidney, and urothelial cells of the bladder. [47]  The viral attachment process is followed by priming the spike protein S2 subunit by the host transmembrane serine protease 2 (TMPRSS2) that facilitates cell entry and subsequent viral replication. [48]

In the early phase of the infection, viral replication results in direct virus-mediated tissue damage. In the late phase, the infected host cells trigger an immune response by recruiting T lymphocytes, monocytes, and neutrophils. Cytokines such as tumor necrosis factor-α (TNF α), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 (IL-1), interleukin-6 (IL-6), ), IL-1β, IL-8, IL-12 and interferon (IFN)-γ are released. In severe COVID-19 illness, a 'cytokine storm' is seen. This is due to the over-activation of the immune system and high levels of cytokines in circulation. This results in a local and systemic inflammatory response. [49] [50]  

Effect of SARS-CoV-2 on the Respiratory System

Increased vascular permeability and subsequent development of pulmonary edema in patients with severe COVID-19 are explained by multiple mechanisms. [51] [52] [53]  These mechanisms include:

• Endotheliitis as a result of direct viral injury and perivascular inflammation leading to microvascular and microthrombi deposition
• Dysregulation of RAAS due to increased binding of the virus to the ACE2 receptors
• Activation of the kallikrein-bradykinin pathway, the activation of which enhances vascular permeability
• Enhanced epithelial cell contraction causes swelling of cells and disturbance of intercellular junctions
• The binding of SARS-CoV-2 to the Toll-Like Receptor (TLR) induces the release of pro-IL-1β, which mediates lung inflammation until fibrosis . [54]

Effect of SARS-CoV-2 on Extrapulmonary Organ Systems

Although the respiratory system is the principal target for SARS-CoV-2, other major organ systems such as the gastrointestinal tract (GI), hepatobiliary, cardiovascular, renal, and central nervous systems may also be affected. SARS-CoV-2–induced organ dysfunction is likely due to a combination of mechanisms, such as direct viral toxicity, ischemic injury caused by vasculitis, thrombosis, immune dysregulation, and renin-angiotensin-aldosterone system (RAAS) dysregulation. [55]

Cardiac involvement in COVID-19 is common and likely multifactorial. ACE2 receptors exhibited by myocardial cells may cause direct cytotoxicity to the myocardium leading to myocarditis. Proinflammatory cytokines such as IL-6 can also lead to vascular inflammation, myocarditis, and cardiac arrhythmias. [56]

Acute coronary syndrome (ACS) is a well-recognized cardiac manifestation of COVID-19. It is likely due to multiple factors, including proinflammatory cytokines, worsening of preexisting severe coronary artery disease, coronary plaque destabilization, microthrombogenesis, and reduced coronary blood flow. [57]  

SARS-CoV-2 has a significant effect on the hematological and hemostatic systems as well. The mechanism of leukopenia, one of the most common laboratory abnormalities encountered in COVID-19, is unknown. Several hypotheses have been postulated that include ACE 2 mediated lymphocyte destruction by direct invasion by the virus, lymphocyte apoptosis due to proinflammatory cytokines, and possible invasion of the virus in the lymphatic organs. [58]  

Thrombocytopenia is common in COVID-19 and is likely due to multiple factors, including virus-mediated suppression of platelets, autoantibodies formation, and coagulation cascade activation, resulting in platelet consumption. [59]  

Thrombocytopenia and neutrophilia are considered a hallmark of severe illness. [55] Although it is well known that COVID-19 is associated with a state of hypercoagulability, the exact mechanisms that lead to the activation of the coagulation system are unknown and likely attributed to the cytokine-induced inflammatory response. The pathogenesis of this associated hypercoagulability is multifactorial. The hypercoagulability is probably induced by direct viral-mediated damage or cytokine-induced injury of the vascular endothelium leading to the activation of platelets, monocytes, and macrophages, with increased expression of von Willebrand factor and Factor VIII that results in the generation of thrombin and formation of a fibrin clot. [59] [60]  

Other mechanisms that have been proposed include possible mononuclear phagocyte-induced prothrombotic sequelae, derangements in the renin-angiotensin system (RAS) pathways, and complement-mediated microangiopathy. [59]

• History and Physical

Clinical Manifestations of COVID-19

• The median incubation period for SARS-CoV-2 is estimated to be 5.1 days, and most patients will develop symptoms within 11.5 days of infection. [61]
• The clinical spectrum of COVID-19 varies from asymptomatic or paucisymptomatic forms to clinical illness characterized by acute respiratory failure requiring mechanical ventilation, septic shock, and multiple organ failure. 
• It is estimated that 17.9% to 33.3% of infected patients will remain asymptomatic. [62] [63]
• Most symptomatic patients present with fever, cough, and shortness of breath. Less common symptoms include sore throat, anosmia, dysgeusia, anorexia, nausea, malaise, myalgias, and diarrhea. Stokes et al. reported that among 373,883 confirmed symptomatic COVID-19 cases in the USA, 70% experienced fever, cough, and shortness of breath, 36% reported myalgia, and 34% reported headache. [35]
• A large meta-analysis evaluating clinicopathological characteristics of 8697 patients with COVID-19 in China reported laboratory abnormalities that included lymphopenia (47.6%), elevated C-reactive protein levels (65.9%), elevated cardiac enzymes (49.4%), and abnormal liver function tests (26.4%). Other laboratory abnormalities included leukopenia (23.5%), elevated D-dimer (20.4%), elevated erythrocyte sedimentation rate (20.4%), leukocytosis (9.9%), elevated procalcitonin (16.7%), and abnormal renal function (10.9%). [64]
• A meta-analysis of 212 published studies with 281,461 individuals from 11 countries/regions reported that severe disease course was noted in about 23% of the patients, with a mortality rate of about 6% in patients infected with COVID-19. [65]
• An elevated neutrophil-to-lymphocyte ratio (NLR), an elevated derived NLR ratio (d-NLR), and an elevated platelet-to-lymphocyte ratio indicate a cytokine-induced inflammatory storm. [66]

Based on the severity of the presenting illness, which includes clinical symptoms, laboratory and radiographic abnormalities, hemodynamics, and organ function, the National Institutes of Health (NIH) issued guidelines that classify COVID-19 into 5 distinct types.[ NIH COVID-19 Treatment Guidelines ]

• Asymptomatic or Presymptomatic Infection : Individuals with positive SARS-CoV-2 test without any clinical symptoms consistent with COVID-19.
• Mild illness : Individuals who have symptoms of COVID-19, such as fever, cough, sore throat, malaise, headache, muscle pain, nausea, vomiting, diarrhea, anosmia, or dysgeusia but without shortness of breath or abnormal chest imaging.
• Moderate illness : Individuals with clinical symptoms or radiologic evidence of lower respiratory tract disease and oxygen saturation (SpO 2 ) ≥94% on room air.
• Severe illness : Individuals who have SpO 2 less than 94% on room air, a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO 2 /FiO 2 ) of less than 300, marked tachypnea with a respiratory frequency of greater than 30 breaths/min, or lung infiltrates that are greater than 50% of total lung volume.
• Critical illness : Individuals with acute respiratory failure, septic shock, or multiple organ dysfunction. Patients with severe COVID-19 illness may become critically ill with the development of acute respiratory distress syndrome (ARDS). This tends to occur approximately one week after the onset of symptoms.

ARDS is characterized by a severe new-onset respiratory failure or worsening of an already identified respiratory picture. The diagnosis requires bilateral opacities (lung infiltrates >50%), not fully explained by effusions or atelectasis. The Berlin definition classifies ARDS into 3 types based on the degree of hypoxia, with the reference parameter being PaO 2 /FiO 2 or P/F ratio: [67]

• Mild ARDS : 200 mm Hg <PaO 2 /FiO 2 ≤300 mm Hg in patients not receiving mechanical ventilation or in those managed through noninvasive ventilation (NIV) by using positive end-expiratory pressure (PEEP) or a continuous positive airway pressure (CPAP) ≥5 cm H2O.
• Moderate ARDS : 100 mm Hg <PaO 2 /FiO 2 ≤200 mm Hg
• Severe ARDS : PaO 2 /FiO 2 ≤100 mm Hg

When PaO 2 is unavailable, a ratio of SpO 2 /FiO 2 ≤315 suggests ARDS. A multicenter prospective observational study that analyzed 28-day mortality in mechanically ventilated patients with ARDS concluded that COVID-19 patients with ARDS had features similar to other ARDS cohorts, and the risk of 28-day mortality increased with ARDS severity. [68]

Extrapulmonary Manifestations 

• Acute kidney injury (AKI) is the most frequently encountered extrapulmonary manifestation of COVID-19 and is associated with an increased mortality risk. [69] A large multicenter cohort study of hospitalized patients with COVID-19 that involved 5,449 patients admitted with COVID-19 reported that 1993 (36.6%) patients developed AKI during their hospitalization, of which 14.3% of patients required renal replacement therapy (RRT). [70]  
• Myocardial injury manifesting as myocardial ischemia/infarction (MI) and myocarditis are well-recognized cardiac manifestations in patients with COVID-19. Single-center retrospective study analysis of 187 patients with confirmed COVID-19 reported that 27.8% of patients exhibited myocardial injury indicated by elevated troponin levels. The study also noted that patients with elevated troponin levels had more frequent malignant arrhythmias and a higher mechanical ventilation frequency than patients with normal troponin levels. [71]  A meta-analysis of 198 published studies involving 159698 COVID-19 patients reported that acute myocardial injury and a high burden of pre-existing cardiovascular disease were significantly associated with higher mortality and ICU admission. [72]
• Lymphopenia is a common laboratory abnormality in most patients with COVID-19. Other laboratory abnormalities include thrombocytopenia, leukopenia, elevated ESR levels, C-reactive protein (CRP), lactate dehydrogenase (LDH), and leukocytosis.
• COVID-19 is also associated with a hypercoagulable state, evidenced by the high prevalence of venous thromboembolic events. COVID-19 is associated with markedly elevated D-dimer and fibrinogen levels and prolonged prothrombin time (PT) and partial thromboplastin time (aPTT). [71] [55]  
• GI symptoms (such as diarrhea, nausea, vomiting), anorexia, and abdominal pain are common. A meta-analysis reported that the weighted pool prevalence of diarrhea was 12.4% (95% CI, 8.2% to 17.1%), nausea or vomiting was 9% (95% CI, 5.5% to 12.9%), loss of appetite was 22.3% (95% CI, 11.2% to 34.6%) and abdominal pain was 6.2% (95% CI, 2.6% to 10.3%). The study also reported that the mortality rate among patients with GI symptoms was similar to the overall mortality rate. [73] Cases of acute mesenteric ischemia and portal vein thrombosis have also been described. [74]
• An acute increase in aspartate transaminase (AST) and alanine transaminase (ALT) is noted in 14% to 53% of patients with COVID-19 infection. [75]
• Guillain-Barré syndrome (GBS) cases from Northern Italy have also been reported. [76] [77]
• Acral lesions resembling pseudo chilblains (40.4%) are the most common cutaneous manifestation noted in patients with COVID-19. [78]
• Other cutaneous manifestations include erythematous maculopapular rash (21.3%), vesicular rashes (13%), urticarial rashes (10.9%), vascular rashes (4%) resembling livedo or purpura, and erythema multiforme-like eruptions (3.7%). [78]

Diagnostic Testing in COVID-19

A nasopharyngeal swab for SARS-CoV-2 nucleic acid using a real-time PCR assay is the standard diagnostic test.[ NIH COVID-19 Treatment Guidelines ] Commercial PCR assays have been authorized by the USA Food and Drug Administration (FDA) for the qualitative detection of SARS-CoV-2 virus using specimens obtained from nasopharyngeal swabs as well as other sites such as oropharyngeal, anterior/mid-turbinate nasal swabs, nasopharyngeal aspirates, bronchoalveolar lavage (BAL) and saliva. 

The sensitivity of PCR testing depends on multiple factors, including the specimen's adequacy, time from exposure, and specimen source. [79]  However, the specificity of most commercial FDA-authorized SARS-CoV-2 PCR assays is nearly 100%, provided there is no cross-contamination during specimen processing. SARS-CoV-2 antigen tests are less sensitive but have a faster turnaround time than molecular PCR testing. [80]  

Despite the numerous antibody tests designed to date, serologic testing has limitations in specificity and sensitivity, and results from different tests vary. According to the NIH guidelines, diagnosing acute SARS-CoV-2 infection based on serologic testing is not recommended. They also stated that there is insufficient evidence to recommend for or against using serologic testing to assess immunity, even if it is used to guide clinical decisions about COVID-19 vaccines/monoclonal antibodies.[ NIH COVID-19 Treatment Guidelines ]

Other Laboratory Assessment

• Complete blood count (CBC), a comprehensive metabolic panel (CMP) that includes renal and liver function testing, and a coagulation panel should be performed in all hospitalized patients.
• Additional tests, such as ESR, C-reactive protein (CRP), ferritin, lactate dehydrogenase, and procalcitonin, can be considered in hospitalized patients. However, their prognostic significance in COVID-19 is not clear.
• A D-dimer level is required as it guides the use of therapeutic versus prophylactic doses of anticoagulation.

Imaging ModalitiesThis s viral illness commonly manifests as pneumonia, so radiological imaging such as chest x-rays, lung ultrasounds, and chest computed tomography (CT) are often obtained. However, there are no guidelines regarding the timing and choice of pulmonary imaging in patients with COVID-19.

When obtained, the chest X-ray usually shows bilateral multifocal alveolar opacities. Pleural effusions can also be demonstrated. The most common CT chest findings in COVID-19 are multifocal bilateral ground glass opacities with consolidation changes, usually in a patchy peripheral distribution. [81]

Radiologic imaging is not a sensitive method for detecting this disease. A retrospective study of 64 patients with documented COVID-19 reported that 20% had no abnormalities on chest radiographs during the illness. [82]  A chest CT is more sensitive than a radiograph but is not specific. No finding on radiographic imaging can completely rule in or rule out COVID-19 illness. Therefore the American College of Radiology (ACR) advises against the routine use of chest CT for screening or diagnosis of COVID-19.[ ACR Position Statement for Diagnosis of COVID-19 ]

• Treatment / Management

According to the National Institutes of Health (NIH), the 2 main processes driving the pathogenesis of COVID-19 include replication of the virus in the early phase of the illness and dysregulated immune/inflammatory response to SARS-CoV-2 that leads to systemic tissue damage in the later phase of the disease.[ NIH COVID-19 Treatment Guidelines ] The guidelines, therefore, advise antiviral medications to halt viral replication in the early phase of the illness and immunomodulators in the later phase.

Remdesivir is the only antiviral drug approved by the USA Food and Drug Administration (FDA) to treat COVID-19. Ritonavir-boosted nirmatrelvir, molnupiravir, and high-titer COVID-19 convalescent plasma have Emergency Use Authorizations (EUAs) for treating COVID-19. Tixagevimab 300 mg plus cilgavimab 300 mg monoclonal antibodies have received EUAs that allow them to be used as SARS-CoV-2 preexposure prophylaxis (PrEP) in certain patients.

Many other monoclonal antibodies had EUAs; however, as Omicron subvariants emerged, their EUAs were revoked as they were no longer effective. 

The most recent NIH treatment guidelines for the management of COVID-19 illness (accessed on January 3rd, 2023) are outlined below:[ NIH COVID-19 Treatment Guidelines ]

Nonhospitalized Adults With Mild-to-Moderate COVID-19 Illness Who Do Not Require Supplemental Oxygen

• The NIH recommends against using dexamethasone or any other systemic corticosteroids in patients who are not hypoxic. [83]   
• Ritonavir-boosted nirmatrelvir is a combination of oral protease inhibitors. It has been shown to reduce hospitalization and death when given to high-risk, unvaccinated, nonhospitalized patients. It must be given within 5 days of symptoms onset. [84]
• It is a strong cytochrome P450 inhibitor with many drug-drug interactions that must be carefully assessed.
• Some interactions can be managed by temporarily holding the medication, some may be managed with dose adjustment, but some may warrant the use of alternate COVID-19 therapy. 
• Ritonavir-boosted nirmatrelvir is not recommended in patients with an estimated glomerular filtration rate (eGFR) of less than 30 mL/min.
• The recommended dose is nirmatrelvir 300 mg with ritonavir 100 mg orally twice daily for 5 days.
• This is a nucleotide analog that inhibits the SARS-CoV-2 RNA polymerase  
• The recommended duration of therapy in this setting is 3 days.
• The recommended dose is 200 mg IV on day 1, followed by 100 mg IV for 2 more days.
• It is a mutagenic ribonucleoside antiviral agent.
• Fetal toxicity has been reported in animal studies with this agent. Due to the risk of genotoxicity with this agent, it is not recommended in pregnant patients. 
• This agent should only be used if both therapies are unavailable or cannot be given.
• The NIH guidelines recommend against using anti-SARS-CoV-2 monoclonal antibodies (mAbs) for treating COVID-19 in this cohort because the Omicron subvariants are not susceptible to these agents.  
• Adequate and close medical follow-up is recommended; however, the frequency and duration of follow-up depend on individual risk factors and the severity of their symptoms. 
• Risk factors for progression to severe disease include advanced age and underlying medical conditions. The CDC maintains an updated list of medical conditions associated with a high risk of progression. 
•  Asthma
• Cerebrovascular disease
• Chronic kidney disease
• Bronchiectasis
• COPD (Chronic obstructive pulmonary disease)
• Interstitial lung disease
• Pulmonary embolism
• Pulmonary hypertension
• Nonalcoholic fatty liver disease
• Alcoholic liver disease
• Autoimmune hepatitis
• Cystic fibrosis
• Diabetes, type 1 and 2
• Heart conditions (such as heart failure, coronary artery disease, or cardiomyopathies)
• HIV (Human immunodeficiency virus)
• Mental health conditions such as mood disorders and Schizophrenia spectrum disorders
• Obesity (defined as body mass index (BMI) of greater than 30 kg/m 2 or greater than 95th percentile in children)
• Pregnancy and recent pregnancy
• Smoking, current and former
• Solid organ or blood stem cell transplantation
• Tuberculosis
• Use of corticosteroids or other immunosuppressive medications ( CDC: Underlying Medical Conditions Associated with Higher Risk )

Therapeutic Management of Hospitalized Adults With COVID-19   Who Do Not Require Oxygen

• If patients are hospitalized for reasons other than COVID-19 illness and are not on oxygen, their management is similar to nonhospitalized patients. 
• If they are hospitalized for COVID-19 illness but do not require oxygen, the NIH advises against the use of dexamethasone or any other systemic corticosteroid.
• A prophylactic dose of anticoagulation should be given if there is no contraindication. 
• If they are hospitalized for COVID-19 illness, do not require oxygen, but are at high risk of progression to severe disease, they should be treated with remdesivir.
• The benefit of remdesivir is greatest when given early, ideally within ten days of symptom onset.
• Remdesivir should be given for 5 days or until hospital discharge. 

Therapeutic Management of Hospitalized Adults With COVID-19 Who Require Conventional Oxygen

• Conventional oxygen is defined as oxygen that is NOT high-flow nasal cannula, noninvasive mechanical ventilation, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)
• For most patients in this cohort, the recommended treatment is dexamethasone plus remdesivir.
• Dexamethasone dose is 6 mg IV or oral (PO) once daily for up to 10 days or until hospital discharge (dexamethasone should not be continued at discharge). [83]  
• If the patient is on minimal oxygen, remdesivir monotherapy (without dexamethasone) should be used. 
• If remdesivir cannot be obtained or given, dexamethasone monotherapy is recommended.
• If dexamethasone is unavailable, corticosteroids such as prednisone, methylprednisolone, or hydrocortisone may be used.
• If the patient is already receiving dexamethasone but has rapidly increasing oxygen needs and/or signs of systemic inflammation, oral baricitinib or intravenous (IV) tocilizumab should be added to the treatment regimen as these agents have been shown to improve outcomes in rapidly decompensating patients. [85]
• Alternate immunomodulatory agents for this cohort include oral tofacitinib and IV sarilumab. These agents should only be used if baricitinib and tocilizumab are not available. 
• If the D-dimer level is above normal in this cohort of patients, they recommend therapeutic anticoagulation if the patient is not pregnant and has no increased risk of bleeding. Contraindications for therapeutic anticoagulation in these patients include a platelet count of less than 50 x10^9 /L, hemoglobin less than 8 g/dL, use of dual antiplatelet therapy, any significant bleeding within the past 30 days, a history of a bleeding disorder or an inherited or active acquired bleeding disorder. 
• For pregnant patients, a prophylactic dose of anticoagulation is recommended.

Therapeutic Management of Hospitalized Adults With COVID-19 who Require High-flow Nasal Cannula (HFNC) or Noninvasive Mechanical Ventilation (NIV)

• A meta-analysis study evaluating the effectiveness of HFNC compared to conventional oxygen therapy and NIV before mechanical ventilation reported that HFNC, when used before mechanical ventilation, could improve the prognosis of patients compared to conventional oxygen therapy and NIV. [86]  HFNC or NIV is associated with decreased dispersion of exhaled air, especially when used with good interface fitting, thus creating a low risk of nosocomial transmission of the infection. [87]  However, these treatment modalities are associated with a greater risk of aerosolization and should be used in negative-pressure rooms. [88]
• According to the NIH, dexamethasone plus oral baricitinib or dexamethasone plus IV tocilizumab are the preferred treatment regimens in these patients.
• Alternate immunomodulatory agents for this cohort include oral tofacitinib and IV sarilumab.
• Dexamethasone monotherapy is recommended if baricitinib, tocilizumab, or sarilumab cannot be obtained/given.
• Clinicians may consider adding remdesivir to corticosteroid and immunomodulator combination regimens in immunocompromised patients who require HFNC or NIV ventilation; however, using remdesivir without immunomodulators is not recommended.
• A prophylactic dose of anticoagulation is recommended in these patients. 
• If patients were started on a therapeutic dose of heparin while on conventional oxygen therapy, they should be switched to prophylactic dosing at this time unless they have another indication for full anticoagulation.

Therapeutic Management of Hospitalized Adults With COVID-19 who Require Mechanical Ventilation (MV)

• The management of this cohort is the same as those requiring HFNC or NIV, except that remdesivir is not recommended. 
• Remdesivir is most effective earlier in the course of the disease and in patients not on mechanical ventilation or ECMO.
• According to the NIH, one study showed a slight trend toward an increase in mortality in patients who received remdesivir while on mechanical ventilation or ECMO. [89]
• With this data in mind, the NIH recommends against using remdesivir in patients receiving MV or ECMO; however, if the patient was started on remdesivir and progressed to requiring mechanical ventilation or ECMO, they recommended continuing remdesivir to complete the treatment course. 

High-Titer COVID-19 Convalescent Plasma (CCP)

• The United States Food and Drug Administration (FDA) approved convalescent plasma therapy under a EUA for patients with severe life-threatening COVID-19. [90] [91]   Data from multiple studies evaluating the use of convalescent plasma in life-threatening COVID-19 has generated mixed results. Data from 3 small randomized control trials showed no significant differences in clinical improvement or overall mortality in patients treated with convalescent plasma versus standard therapy. [92] [93] [94]  
• According to the NIH, high-titer CCP is not recommended in immunocompetent individuals.
• However, the NIH states that some experts consider it appropriate for use in immunocompromised individuals. Therefore, the current NIH guidelines state that there is insufficient evidence for or against the use of high-titer CCP for treating COVID-19 in hospitalized or nonhospitalized patients who are immunocompromised.

Medications/Treatments That Should NOT Be Used for the Treatment of COVID-19 According to the Latest NIH Guidelines [ NIH COVID-19 Treatment Guidelines ]

• Chloroquine or hydroxychloroquine with or without azithromycin
• Lopinavir/ritonavir
• Azithromycin
• Doxycycline
• Fluvoxamine
• Inhaled corticosteroids
• Excess supplementation of vitamin C, vitamin D, and zinc
• Interferons alfa, beta, or lambda
• Nitazoxanide
• Bamlanivimab plus etesevimab
• Bebtelovimab
• Casirivimab plus imdevimab

Preexposure Prophylaxis for SARS-CoV-2 Infection

• According to the NIH guidelines, tixagevimab plus cilgavimab is authorized by the FDA for preexposure prophylaxis of SARS-CoV-2 in people who are not expected to mount an adequate immune response to COVID-19 vaccination; however, the prevalence of Omicron subvariants that are resistant to tixagevimab plus cilgavimab is noted to be increasing rapidly. 
• In the absence of alternative options, the NIH still recommends tixagevimab 300 mg plus cilgavimab 300 mg at this time.
• Tixagevimab and cilgavimab are potent anti-spike neutralizing monoclonal antibodies obtained from antibodies isolated from B cells of patients infected with SARS-CoV-2 that have demonstrated neutralizing activity against SARS-CoV-2 virus by binding to nonoverlapping epitopes of the viral spike-protein RBD. [95] [96] [97]  
• The EUA authorizes its use in adult and pediatric patients with no current evidence of SARS-CoV-2 infection and no recent exposure to SARS-CoV-2-positive individuals. They must be moderately or severely immunocompromised or be on immunosuppressive medications.
• Differential Diagnosis

The symptoms of the early stages of the disease are nonspecific. Differential diagnosis should include the possibility of a wide range of infectious and noninfectious respiratory disorders.

• Community-acquired bacterial pneumonia
• Viral pneumonia 
• Influenza infection
• Aspiration pneumonia
• Pneumocystis jirovecii pneumonia
• Middle East respiratory syndrome (MERS)
• Avian influenza A (H7N9) viral infection
• Avian influenza A (H5N1) viral infection
• Pulmonary tuberculosis

The prognosis of COVID-19 depends on various factors, including the patient's age, the severity of illness at presentation, preexisting conditions, how quickly treatment can be implemented, and response to treatment. The WHO currently estimates the global case fatality rate for COVID-19 is 2.2%. Results from a European multicenter prospective cohort study that included 4000 critically ill patients with COVID-19 reported a 90-day mortality of 31%, with higher mortality noted in geriatric patients and patients with diabetes, obesity, and severe ARDS. [98]

• Complications

COVID-19 is a systemic viral illness based on its involvement in multiple major organ systems.

• Patients with advanced age and comorbid conditions such as obesity, diabetes mellitus, chronic lung disease, cardiovascular disease, chronic kidney disease, chronic liver disease, and neoplastic conditions are at risk of developing severe COVID-19 and its associated complications. The most common complication of severe COVID-19 illness is progressive or sudden clinical deterioration leading to acute respiratory failure and ARDS or multiorgan failure leading to death.
• Patients with COVID-19 illness are also at increased risk of developing prothrombotic complications such as pulmonary embolisms, myocardial infarctions, ischemic strokes, and arterial thrombosis. [55]
• Cardiovascular system involvement results in malignant arrhythmias, cardiomyopathy, and cardiogenic shock.
• GI complications such as bowel ischemia, transaminitis, gastrointestinal bleeding, pancreatitis, Ogilvie syndrome, mesenteric ischemia, and severe ileus are often noted in critically ill patients with COVID-19. [99]
• Acute renal failure is the most common extrapulmonary manifestation of COVID-19 and is associated with an increased mortality risk. [69]
• A meta-analysis study of 14 studies evaluating the prevalence of disseminated intravascular coagulation (DIC) in hospitalized patients with COVID-19 reported that DIC was observed in 3% (95%: 1%-5%, P <0.001) of the included patients. Additionally, DIC was noted to be associated with severe illness and was a poor prognostic indicator. [100]
• More recent data have emerged regarding prolonged symptoms in patients who have recovered from COVID-19 infection, termed "post-acute COVID-19 syndrome." A large cohort study of 1773 patients performed 6 months after hospitalization with COVID-19 revealed that most exhibited at least one persistent symptom: fatigue, muscle weakness, sleep difficulties, or anxiety. Patients with severe illness also had an increased risk of chronic lung issues. [101]
• A retrospective cohort study that included 236,379 patients reported substantial neurological (intracranial hemorrhage, ischemic stroke) and psychiatric morbidity (anxiety disorder, psychotic disorder) 6 months after being diagnosed with COVID-19. [102]
• Secondary invasive fungal infections such as COVID-19-associated pulmonary aspergillosis and rhino-cerebro-orbital mucormycosis have increasingly been reported as complications in patients recovering from COVID-19. Risk factors for developing secondary fungal infection include comorbid conditions such as uncontrolled diabetes, associated lymphopenia, and excessive use of corticosteroids.
• Deterrence and Patient Education

The NIH COVID-19 Treatment Guidelines recommend COVID-19 vaccination as soon as possible for all eligible individuals. The CDC’s Advisory Committee on Immunization Practices (AI) determines eligibility eligibility. Four vaccines are authorized or approved in the United States to prevent COVID-19. According to the NIH guidelines, the preferred vaccines include:[ NIH COVID-19 Treatment Guidelines ]

• mRNA vaccine BNT162b2 (Pfizer-BioNTech)
• mRNA-1273 (Moderna)
• Recombinant spike protein with matrix-M1 adjuvant vaccine NVX-CoV2373 (Novavax)

The adenovirus vector vaccine Ad26.COV2.S (Johnson & Johnson/Janssen) is less preferred due to its risk of serious adverse events.[ NIH COVID-19 Treatment Guidelines ]

A primary series of COVID-19 vaccination is recommended for everyone older than 6 months in the United States. Bivalent mRNA vaccines that protect against the original SARS-CoV-2 virus strain and Omicron subvariants are recommended at least 2 months after receiving the primary vaccine series or a booster dose.[ NIH COVID-19 Treatment Guidelines ] 

• Enhancing Healthcare Team Outcomes

SARS-CoV-2 and its variants continue to cause significant morbidity and mortality worldwide. Prevention and management of this highly transmissible respiratory viral illness require a holistic and interprofessional approach that includes physicians' expertise across specialties, nurses, pharmacists, public health experts, and government authorities. There should be open communication among the clinical providers, pharmacists, and nursing staff while managing patients with COVID-19. Each team member should strive to keep abreast of the latest recommendations and guidelines and be free to speak up if they notice anything that does not comply with the latest tenets for managing COVID patients; there is no place for a hierarchy in communication that prohibits any team member from voicing their concerns. This open interprofessional approach will yield the best outcomes. 

Clinical providers managing COVID-19 patients on the frontlines should keep themselves periodically updated with the latest clinical guidelines about diagnostic and therapeutic options available in managing COVID-19, especially considering the emergence of new SARS-CoV-2 variants, which could significantly impact morbidity and mortality. Continued viral surveillance of new variants is crucial at regular intervals with viral genomic sequencing, given the possibility that more highly transmissible, more virulent, and treatment-resistant variants could emerge that can have a more catastrophic effect on global health in addition to the current scenario. A multi-pronged approach involving interprofessional team members can improve patient care and outcomes for this potentially devastating disease and help the world end this pandemic.

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Disclosure: Marco Cascella declares no relevant financial relationships with ineligible companies.

Disclosure: Michael Rajnik declares no relevant financial relationships with ineligible companies.

Disclosure: Abdul Aleem declares no relevant financial relationships with ineligible companies.

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Disclosure: Raffaela Di Napoli declares no relevant financial relationships with ineligible companies.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

• Cite this Page Cascella M, Rajnik M, Aleem A, et al. Features, Evaluation, and Treatment of Coronavirus (COVID-19) [Updated 2023 Aug 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

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What you need to know about covid-19 vaccines, answers to the most common questions about coronavirus vaccines..

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Vaccines save millions of lives each year. The development of safe and effective COVID-19 vaccines are a crucial step in helping us get back to doing more of the things we enjoy with the people we love.

We’ve gathered the latest expert information to answer some of the most common questions about COVID-19 vaccines. Keep checking back as we will update this article as more information becomes available.

What are the benefits of getting vaccinated?

Vaccines save millions of lives each year and a COVID-19 vaccine could save yours. The COVID-19 vaccines are safe and effective, providing strong protection against serious illness and death. WHO reports that unvaccinated people have at least 10 times higher risk of death from COVID-19 than someone who has been vaccinated. 

It is important to be vaccinated as soon as it’s your turn, even if you already had COVID-19. Getting vaccinated is a safer way for you to develop immunity from COVID-19 than getting infected.

The COVID-19 vaccines are highly effective, but no vaccine provides 100 per cent protection. Some people will still get ill from COVID-19 after vaccination or pass the virus onto someone else. 

Therefore, it is important to continue practicing safety precautions to protect yourself and others, including avoiding crowded spaces, physical distancing, hand washing and wearing a mask.

Who should be vaccinated first?

Each country must identify priority populations, which WHO recommends are frontline health workers (to protect health systems) and those at highest risk of death due to COVID-19, such as older adults and people with certain medical conditions. Other essential workers, such as teachers and social workers, should then be prioritized, followed by additional groups as more vaccine doses become available.

The risk of severe illness from COVID-19 is very low amongst healthy children and adolescents, so unless they are part of a group at higher risk of severe COVID-19, it is less urgent to vaccinate them than these priority groups.

Children and adolescents who are at higher risk of developing severe illness from COVID-19, such as those with underlying illnesses, should be prioritized for COVID-19 vaccines.  

When shouldn’t you be vaccinated against COVID-19?

If you have any questions about whether you should receive a COVID-19 vaccine, speak to your healthcare provider. At present, people with the following health conditions should not receive a COVID-19 vaccine to avoid any possible adverse effects:

• If you have a history of severe allergic reactions to any ingredients of a COVID-19 vaccine.
• If you are currently sick or experiencing symptoms of COVID-19 (although you can get vaccinated once you have recovered and your doctor has approved).

Should I get vaccinated if I already had COVID-19?

Yes, you should get vaccinated even if you’ve previously had COVID-19. While people who recover from COVID-19 may develop natural immunity to the virus, it is still not certain how long that immunity lasts or how well it protects you against COVID-19 reinfection. Vaccines offer more reliable protection, especially against severe illness and death. Vaccination policies after COVID-19 infection vary by country. Check with your health care provider on the recommendation where you live.

Which COVID-19 vaccine is best for me?

All WHO-approved vaccines have been shown to be highly effective at protecting you against severe illness and death from COVID-19. The best vaccine to get is the one most readily available to you.

You can find a list of those approved vaccines on WHO’s site .  

Remember, if your vaccination involves two doses, it’s important to receive both to have the maximum protection. 

How do COVID-19 vaccines work?

Vaccines work by mimicking an infectious agent – viruses, bacteria or other microorganisms that can cause a disease. This ‘teaches’ our immune system to rapidly and effectively respond against it.

Traditionally, vaccines have done this by introducing a weakened form of an infectious agent that allows our immune system to build a memory of it. This way, our immune system can quickly recognize and fight it before it makes us ill. That’s how some of the COVID-19 vaccines have been designed.

Other COVID-19 vaccines have been developed using new approaches, which are called messenger RNA, or mRNA, vaccines. Instead of introducing antigens (a substance that causes your immune system to produce antibodies), mRNA vaccines give our body the genetic code it needs to allow our immune system to produce the antigen itself. mRNA vaccine technology has been studied for several decades. They contain no live virus and do not interfere with human DNA.

For more information on how vaccines work, please visit WHO .

Are COVID-19 vaccines safe?

Yes, COVID-19 vaccines have been safely used to vaccinate billions of people. The COVID-19 vaccines were developed as rapidly as possible, but they had to go through rigorous testing in clinical trials to prove that they meet internationally agreed benchmarks for safety and effectiveness. Only if they meet these standards can a vaccine receive validation from WHO and national regulatory agencies.

UNICEF only procures and supplies COVID-19 vaccines that meet WHO’s established safety and efficacy criteria and that have received the required regulatory approval.

How were COVID-19 vaccines developed so quickly?

Scientists were able to develop safe effective vaccines in a relatively short amount of time due to a combination of factors that allowed them to scale up research and production without compromising safety: 

• Because of the global pandemic, there was a larger sample size to study and tens of thousands of volunteers stepped forward 
• Advancements in technology (like mRNA vaccines) that were years in the making 
• Governments and other bodies came together to remove the obstacle of funding research and development 
• Manufacturing of the vaccines occurred in parallel to the clinical trials to speed up production 

Though they were developed quickly, all COVID-19 vaccines approved for use by the WHO are safe and effective.

What are the side effects of COVID-19 vaccines?

Vaccines are designed to give you immunity without the dangers of getting the disease. Not everyone does, but it’s common to experience some mild-to-moderate side effects that go away within a few days on their own.

Some of the mild-to-moderate side effects you may experience after vaccination include:

• Arm soreness at the injection site
• Muscle or joint aches

You can manage any side effects with rest, staying hydrated and taking medication to manage pain and fever, if needed.

If any symptoms continue for more than a few days then contact your healthcare provider for advice. More serious side effects are extremely rare, but if you experience a more severe reaction, then contact your healthcare provider immediately.

>> Read: What you need to know before, during and after receiving a COVID-19 vaccine

How do I find out more about a particular COVID-19 vaccine?

You can find out more about COVID-19 vaccines on WHO’s website .  

Can I stop taking precautions after being vaccinated?

Keep taking precautions to protect yourself, family and friends if there is still COVID-19 in your area, even after getting vaccinated. The COVID-19 vaccines are highly effective against serious illness and death, but no vaccine is 100% effective.  

The vaccines offer less protection against infection from the Omicron variant, which is now the dominant variant globally, but remain highly effective in preventing hospitalization, severe disease, and death. In addition to vaccination, it remains important to continue practicing safety precautions to protect yourself and others. These precautions include avoiding crowded spaces, physical distancing, hand washing, and wearing a mask (as per local policies).  

Can I still get COVID-19 after I have been vaccinated? What are ‘breakthrough cases’?

A number of vaccinated people may get infected with COVID-19, which is called a breakthrough infection. In such cases, people are much more likely to only have milder symptoms. Vaccine protection against serious illness and death remains strong.

With more infectious virus variants such as Omicron, there have been more breakthrough infections. That’s why it's recommended to continue taking precautions such as avoiding crowded spaces, wearing a mask and washing your hands regularly, even if you are vaccinated. 

And remember, it’s important to receive all of the recommended doses of vaccines to have the maximum protection.

How long does protection from COVID-19 vaccines last?

According to WHO, the effectiveness of COVID-19 vaccines wanes around 4-6 months after the primary series of vaccination has been completed. Taking a booster to strengthen your protection against serious disease is recommended if it is available to you. 

Do the COVID-19 vaccines protect against variants?

The WHO-approved COVID-19 vaccines continue to be highly effective at preventing severe illness and death.

However, the vaccines offer less protection against infection from Omicron, which is the dominant variant globally. That's why it's important to get vaccinated and continue measures to reduce the spread of the virus – which helps to reduce the chances for the virus to mutate – including physical distancing, mask wearing, good ventilation, regular handwashing and seeking care early if you have symptoms. 

Do I need to get a booster shot?  

Booster doses play an important role in protecting against severe disease, hospitalization and death. 

WHO recommends that you take all COVID-19 vaccine doses recommended to you by your health authority as soon as it is your turn, including a booster dose if recommended. 

Booster shots should be given first to high priority groups. Data shows that a booster shot plays a significant role in boosting waning immunity and protecting against severe disease from highly transmissible variants like Omicron. 

If available, an additional second booster shot is also recommended for some groups of people, 4-6 months after the first booster. That includes older people, those who have weakened immune systems, pregnant women and healthcare workers. 

Check with your local health authorities for guidance and the availability of booster shots where you live.  

What do we know about the bivalent COVID-19 booster doses that have been developed to target Omicron?

Bivalent COVID-19 booster shots have now been developed with both the original strain of the coronavirus and a strain of Omicron. These have been designed to better match the Omicron subvariants that have proven to be particularly transmissible. Lab studies have shown that these doses help you to mount a higher antibody response against Omicron. Both Moderna and Pfizer have developed these bivalent vaccines, and some countries have now approved their use.  

Check with your local health authorities for information about the availability of these doses and who can get them where you live. And it’s important to note that the original COVID-19 vaccines continue to work very well and provide strong protection against severe illness from Omicron.  

Can I receive different types of COVID-19 vaccines?  

Yes, however, policies on mixing vaccines vary by country. Some countries have used different vaccines for the primary vaccine series and the booster. Check with your local health authorities for guidance where you live and speak with your healthcare provider if you have any questions on what is best for you. 

I’m pregnant. Can I get vaccinated against COVID-19?

Yes, you can get vaccinated if you are pregnant. COVID-19 during pregnancy puts you at higher risk of becoming severely ill and of giving birth prematurely. 

Many people around the world have been vaccinated against COVID-19 while pregnant or breastfeeding. No safety concerns have been identified for them or their babies. Getting vaccinated while pregnant helps to protect your baby. For more information about receiving a COVID-19 vaccination while pregnant, speak to your healthcare provider.

>> Read: Navigating pregnancy during the COVID-19 pandemic

I’m breastfeeding. Should I get vaccinated against COVID-19?

Yes, if you are breastfeeding you should take the vaccine as soon as it is available to you. It is very safe and there is no risk to the mother or baby. None of the current COVID-19 vaccines have live virus in them, so there is no risk of you transmitting COVID-19 to your baby through your breastmilk from the vaccine. In fact, the antibodies that you have after vaccination may go through the breast milk and help protect your baby. >> Read: Breastfeeding safely during the COVID-19 pandemic

Can COVID-19 vaccines affect fertility?

No, you may have seen false claims on social media, but there is no evidence that any vaccine, including COVID-19 vaccines, can affect fertility in women or men. You should get vaccinated if you are currently trying to become pregnant.

Could a COVID-19 vaccine disrupt my menstrual cycle?

Some people have reported experiencing a disruption to their menstrual cycle after getting vaccinated against COVID-19. Although data is still limited, research is ongoing into the impact of vaccines on menstrual cycles.

Speak to your healthcare provider if you have concerns or questions about your periods.

Should my child or teen get a COVID-19 vaccine?

An increasing number of vaccines have been approved for use in children. They’ve been made available after examining the data on the safety and efficacy of these vaccines, and millions of children have been safely vaccinated around the world. Some COVID-19 vaccines have been approved for children from the age of 6 months old. Check with your local health authorities on what vaccines are authorized and available for children and adolescents where you live.  

Children and adolescents tend to have milder disease compared to adults, so unless they are part of a group at higher risk of severe COVID-19, it is less urgent to vaccinate them than older people, those with chronic health conditions and health workers. 

Remind your children of the importance of us all taking precautions to protect each other, such as avoiding crowded spaces, physical distancing, hand washing and wearing a mask. 

It is critical that children continue to receive the recommended childhood vaccines. 

How do I talk to my kids about COVID-19 vaccines?

News about COVID-19 vaccines is flooding our daily lives and it is only natural that curious young minds will have questions – lots of them. Read our explainer article for help explaining what can be a complicated topic in simple and reassuring terms.

It’s important to note that from the millions of children that have so far been vaccinated against COVID-19 globally, we know that side effects are very rare. Just like adults, children and adolescents might experience mild symptoms after receiving a dose, such as a slight fever and body aches. But these symptoms typically last for just a day or two. The authorized vaccines for adolescents and children are very safe.  

My friend or family member is against COVID-19 vaccines. How do I talk to them?

The development of safe and effective COVID-19 vaccines is a huge step forward in our global effort to end the pandemic. This is exciting news, but there are still some people who are skeptical or hesitant about COVID-19 vaccines. Chances are you know a person who falls into this category.

We spoke to Dr. Saad Omer, Director at the Yale Institute for Global Health, to get his tips on how to navigate these challenging conversations. >> Read the interview

How can I protect my family until we are all vaccinated?

Safe and effective vaccines are a game changer, but even once vaccinated we need to continue taking precautions for the time being to protect ourselves and others. Variants like Omicron have proven that although COVID-19 vaccines are very effective at preventing severe disease, they’re not enough to stop the spread of the virus alone. The most important thing you can do is reduce your risk of exposure to the virus. To protect yourself and your loved ones, make sure to:

• Wear a mask where physical distancing from others is not possible.
• Keep a physical distance from others in public places.
• Avoid poorly ventilated or crowded spaces.
• Open windows to improve ventilation indoors.
• Try and focus on outdoor activities if possible.  
• Wash your hands regularly with soap and water or an alcohol-based hand rub.

If you or a family member has a fever, cough or difficulty breathing, seek medical care early and avoid mixing with other children and adults.  

Can COVID-19 vaccines affect your DNA?

No, none of the COVID-19 vaccines affect or interact with your DNA in any way. Messenger RNA, or mRNA, vaccines teach the cells how to make a protein that triggers an immune response inside the body. This response produces antibodies which keep you protected against the virus. mRNA is different from DNA and only stays inside the cell for about 72 hours before degrading. However, it never enters the nucleus of the cell, where DNA is kept.

Do the COVID-19 vaccines contain any animal products in them?

No, none of the WHO-approved COVID-19 vaccines contain animal products.

I’ve seen inaccurate information online about COVID-19 vaccines. What should I do?

Sadly, there is a lot of inaccurate information online about the COVID-19 virus and vaccines. A lot of what we’re experiencing is new to all of us, so there may be some occasions where information is shared, in a non-malicious way, that turns out to be inaccurate.

Misinformation in a health crisis can spread paranoia, fear and stigmatization. It can also result in people being left unprotected or more vulnerable to the virus. Get verified facts and advice from trusted sources like your local health authority, the UN, UNICEF, WHO.

If you see content online that you believe to be false or misleading, you can help stop it spreading by reporting it to the social media platform.

What is COVAX?

COVAX is a global effort committed to the development, production and equitable distribution of vaccines around the world. No country will be safe from COVID-19 until all countries are protected.

There are 190 countries and territories engaged in the COVAX Facility, which account for over 90 per cent of the world’s population. Working with CEPI, GAVI, WHO and other partners, UNICEF is leading efforts to procure and supply COVID-19 vaccines on behalf of COVAX.  

Learn more about COVAX .

This article was last updated on 25 October 2022. It will continue to be updated to reflect the latest information. 

Related topics

More to explore, covid-19 response.

Resources and information about UNICEF’s response to the COVID-19 pandemic

How to talk to your children about COVID-19 vaccines

Tips for navigating the conversation

How to talk to friends and family about vaccines

Tips for handling tough conversations with your loved ones

COVAX information centre

UNICEF and partners led the largest vaccine procurement and supply operation in history

REVIEW article

Coronavirus disease (covid-19): comprehensive review of clinical presentation.

• 1 Department of Medicine, King Edward Medical University/ Mayo Hospital, Lahore, Pakistan
• 2 Department of Anesthesia and Intensive Care, Post-Graduate Medical Institute/LGH, Lahore, Pakistan
• 3 Rajarshee Chhatrapati Shahu Maharaj Government Medical College, Kolhapur, India
• 4 Department of Medicine, Faculty of Medicine, University of Tlemcen, Tlemcen, Algeria
• 5 School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan
• 6 Institute of Research and Development, Duy Tan University, Da Nang, Vietnam

COVID-19 is a rapidly growing pandemic with its first case identified during December 2019 in Wuhan, Hubei Province, China. Due to the rampant rise in the number of cases in China and globally, WHO declared COVID-19 as a pandemic on 11th March 2020. The disease is transmitted via respiratory droplets of infected patients during coughing or sneezing and affects primarily the lung parenchyma. The spectrum of clinical manifestations can be seen in COVID-19 patients ranging from asymptomatic infections to severe disease resulting in mortality. Although respiratory involvement is most common in COVID-19 patients, the virus can affect other organ systems as well. The systemic inflammation induced by the disease along with multisystem expression of Angiotensin Converting Enzyme 2 (ACE2), a receptor which allows viral entry into cells, explains the manifestation of extra-pulmonary symptoms affecting the gastrointestinal, cardiovascular, hematological, renal, musculoskeletal, and endocrine system. Here, we have reviewed the extensive literature available on COVID-19 about various clinical presentations based on the organ system involved as well as clinical presentation in specific population including children, pregnant women, and immunocompromised patients. We have also briefly discussed about the Multisystemic Inflammatory Syndrome occurring in children and adults with COVID-19. Understanding the various clinical presentations can help clinicians diagnose COVID-19 in an early stage and ensure appropriate measures to be undertaken in order to prevent further spread of the disease.

Introduction

COVID-19 is a growing pandemic with initial cases identified in Wuhan, Hubei province, China toward the end of December 2019. Labeled as Novel Coronavirus 2019 (2019-nCoV) initially by the Chinese Center for Disease Control and Prevention (CDC) which was subsequently renamed as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) due to its homology with SARS-CoV by the International Committee on Taxonomy of Viruses (ICTV) ( 1 , 2 ). The World Health Organization (WHO) later renamed the disease caused by SARS-CoV-2 as Coronavirus Disease-2019 (COVID-19) ( 3 ). COVID-19 is primarily a disease of the respiratory system affecting lung parenchyma with fever, cough, and shortness of breath as the predominant symptoms. Recent studies have shown that it can affect multiple organ systems and cause development of extra-pulmonary symptoms. Presence of extra-pulmonary symptoms can often lead to late diagnosis and sometimes even mis-diagnosis of COVID-19 which can be detrimental to patients. As researchers globally continue to understand COVID-19 and its implications on the human body, knowledge about the various clinical presentations of COVID-19 is paramount in early diagnosing and treatment in order to decrease the morbidity and mortality caused by the disease.

Epidemiology and Pathophysiology

While studying the early transmission dynamics of COVID-19 outbreak in Wuhan, many cases were found to be linked to the Huanan wholesale seafood market. Further investigation revealed <10% of the total cases could be linked to the market which led to the conclusion of human-to-human transmission of the virus occurring through respiratory droplets and contact transmission contributing to the rise in the number of affected individuals ( 4 ). The exponential rise in the number of cases in China and reporting of cases outside China in multiple countries led WHO to declare COVID-19 as a pandemic on 11th March 2020 ( 5 ).

SARS-CoV-2 tends to infect all age groups and is transmitted via direct contact or respiratory droplets generated during coughing or sneezing by the infected patient during both symptomatic or pre-symptomatic phase of infection. Other routes of transmission include fecal-oral route and fomites along with small risk of vertical transmission from mother to child if infection occurs during third trimester of pregnancy ( 6 , 7 ). There has also been evidence of asymptomatic transmission of COVID-19 ( 8 ). The concept of super spreaders in relation to COVID-19 is emerging where a single individual either symptomatic or asymptomatic can infect a disproportionately large number of individuals in an appropriate super spreading conditions such as mass gathering due to production of large number of infectious agent for prolonged duration of time ( 9 ). As per the literature, the incubation period of COVID-19 ranges from 2 to 14 days with a mean incubation period of 3 days ( 10 ). The basic Reproduction number (Ro) of SARS-CoV-2 is 2–2.5. Each individual infected with COVID-19 can infect 2–2.5 other individuals in a naïve population which also explains the exponential growth in the number of cases ( 10 ). The disease tends to be of mild to moderate severity in roughly 80% of patients, and severe disease is associated with infants, elderly patients above 65 years, and patients with other comorbidities such as diabetes mellitus, hypertension, coronary artery disease, and other chronic conditions ( 1 , 2 ). COVID-19 has also been found to be more severe in males than in females with a case fatality rate of 2.8% in males and 1.7% in females ( 11 ). The major organ system affected by the virus is the respiratory system, but it can affect other organ systems either directly or by the effect of host immune response. SARS-CoV-2, the causative agent of COVID-19, after entering the human host initially replicates in the epithelial mucosa of the upper respiratory tract (nose and pharynx) followed by migration to the lungs where further replication of virus occurs causing transient viraemia. The virus uses Angiotensin Converting Enzyme 2 (ACE2) receptor as a primary entry to cells. ACE2 is found abundantly in the mucosal lining of the respiratory tract, vascular endothelial cells, heart, intestine, and kidney. Thus, the virus has potential for replication in all these organs. After entry into cells, the virus undergoes further rapid replication within the target cells and induces extensive epithelial and endothelial dysfunction leading to exponential inflammatory response with the production of a large amount of proinflammatory cytokines and chemokines. Activation of proinflammatory cytokines and chemokines leads to neutrophil activation and migrations and results in the characteristic cytokine storm. The immunological downregulation of ACE2 by the virus contributes to acute lung injury in COVID-19. ACE2 also regulates the renin angiotensin system (RAS); thus, downregulation of ACE2 also causes dysfunction of RAS which contributes to enhanced inflammation ( 2 , 11 – 15 ). These entire factors contribute to symptoms of COVID-19 with sepsis, multi-organ dysfunction, acute respiratory distress syndrome (ARDS), and prothrombotic state leading to an exacerbation of organ dysfunction.

Clinical Manifestation

We review here the system based clinical features of COVID-19.

Respiratory

According to report from WHO-China-Joint Mission on COVID-19, 55,924 laboratories confirmed cases of COVID-19 had fever (87.9%), dry cough (67.7%), fatigue (38.1%), sputum production (33.4%), difficulty breathing (18.6%), sore throat (13.9%), chills (11.4%), nasal congestion (4.8%), and hemoptysis (0.9%) ( 1 ).

Some patients may rapidly progress to acute lung injury and ARDS with septic shock. The median interval between the onset of initial symptoms to development of dyspnea, hospital admission, and ARDS was 5, 7, and 8 days respectively ( 10 ). Some patients with COVID-19 may have reduced oxygen saturation in blood (≤ 93%) with oxygen saturation down to 50 or 60% but remained stable without significant distress, and as such, were termed as salient hypoxia or happy hypoxia ( 16 , 17 ). Trial of oxygen therapy, prone positioning, high flow continuous positive airway pressure, non-re-breathable mask alongside trial of anticoagulation are often used to manage these patients ( 16 , 17 ). However, further study is required to define the role of these strategies in management.

The most frequent radiological abnormality among 975 patients with COVID-19 in computed tomography (CT) scan of chest was ground glass opacity (56.4%) and bilateral patchy shadowing (51.8%) ( 18 ). A scientific review of 2,814 patients have shown that the most common chest CT finding in COVID-19 patients was ground glass opacity followed by consolidation. However, the findings can vary in different patients and at various stages of diseases. Other CT findings include interlobular septal thickening, reticular pattern, crazy paving, etc. Atypical findings like air bronchogram, bronchial wall thickening, nodule, pleural effusion, and lymphadenopathy have also been noted in some studies ( 19 ). A study showed that among 877 patients with non-severe diseases and 173 patients with severe diseases, 17.9 and 2.9% of the patients did not have any detectable radiological abnormalities, respectively ( 18 ).

ENT (Ear, Nose, and Throat)

ENT manifestations are one of the most frequent symptoms encountered by physicians in COVID-19. A peculiar clinical presentation in some COVID-19 patients includes the deterioration of sense, taste (dysgeusia), and loss of smell (anosmia). A systematic review and meta-analysis of 10 studies with 1,627 participants surveyed for olfactory deterioration and 9 studies with 1,390 participants examined for gustatory symptoms demonstrated prevalence of 52.73 and 43.93% of these symptoms among COVID-19 patients, respectively. These clinical features may often present at earlier stages of the disease ( 20 ). Additionally, sore throat, rhinorrhea, nasal congestion, tonsil edema, and enlarged cervical lymph nodes are commonly seen among otolaryngological dysfunctions in patients ( 21 ). A large observational study of 1,099 COVID-19 patients reported tonsils swelling in 23 patients (2.1%), throat congestion in 19 patients (1.7%) and enlarged lymph nodes in 2 patients (0.2%) ( 18 ). This can be explained by the fact that there is a high expression of ACE2 receptors on the epithelial cells of the oral and nasal mucosa including the tongue. It has been known that the novel coronavirus has a strong binding affinity to ACE2 receptors through which it invades host cells ( 22 ). This theory may explain the exhibition of extra-respiratory symptoms including ENT manifestations as part of COVID-19 symptoms.

Cardiovascular

Cardiac manifestation in patient with COVID-19 can occur due to cardiac strain secondary to hypoxia and respiratory failure, direct effect of SARS-CoV-2 on heart or secondary to inflammation and cytokine storm, metabolic derangements, rupture of plaque and coronary occlusion by thrombus, and consequences of drugs used for treatment ( 23 – 25 ). The need for intensive care admission, non-invasive ventilation (46.3 vs. 3.9%), and invasive mechanical ventilation (22 vs. 4.2%) were higher among patients with cardiac ailments as compared to those without cardiac involvement as well as higher hospital mortality than those without myocardial involvement (51.2 vs. 4.5%) ( 26 ). These patients tend to have electrocardiographic (ECG) changes as well as elevations in high sensitivity cardiac troponin (hsCTn) and N- terminal pro-B-type natriuretic peptide (NT proBNP) which corresponded to raised inflammatory markers. Hypertension, acute and fulminant myocarditis, ventricular arrhythmias, atrial fibrillation, stress cardiomyopathy, hypotension and heart failure, acute coronary syndrome (ACS) with ST elevation or depression MI with normal coronaries have been reported ( 23 , 27 ). In a Chinese cohort of 138 patients, 16.7% had arrhythmias with risk higher among those needing ICU care with no mention of the type of arrhythmia that was present ( 28 ). Less frequently, cardiac symptoms like chest pain or tightness and palpitation can be the initial presenting features without fever producing a diagnostic dilemma. Some of these patients eventually go on to develop respiratory symptoms as diseases progress ( 29 ). Patients who have recovered from acute illness may develop arrhythmias as a result of myocardial scar and need future monitoring ( 27 ). One important point to note is use of Renin Angiotensin Aldosterone System (RAAS) modulators in patients with COVID-19. Guidelines from ACC/AHA/HFSA recommends continuing them in high risk patient based on goal directed therapy approach supported by a recent systematic review and meta-analysis conducted by Hasan et. Al. which demonstrated use of ACEI/ARB in COVID-19 patients is associated with lower odds/ hazards of mortality and development of severe/critical diseases as compared to no use of ACEI/ARB ( 30 , 31 ).

Gastrointestinal

In the initial cohort of patients from China, nausea or vomiting and diarrhea were present in 5 and 3.7% of patients ( 1 ). Review of data from 2,023 patients showed anorexia to be the most frequently occurring gastrointestinal symptom in adults. Diarrhea was the most common presenting gastrointestinal symptom in both adults and children while vomiting was found to be more common in children ( 32 ). Other rare symptoms included nausea, abdominal pain, and gastrointestinal bleeding. There have been few instances where COVID-19 patients presented with only gastrointestinal symptoms without the development of fever or respiratory symptoms at the onset and during disease progression ( 33 ). In a smaller cohort of 204 patients, 50.5% had some form of intestinal symptoms and of those, 5.8% had only intestinal symptoms while the remaining patients developed respiratory symptoms subsequently. The most common symptoms reported among them was anorexia (78.64%), non-dehydrating diarrhea (34%), vomiting (3.9%), and abdominal pain (1.94%) ( 34 ). In addition, those with GI symptoms tend to have a longer interval between symptom onset and hospital admission (9 vs. 7.3 days) possibly due to lack of clinical suspicion and delay in diagnosis. Patients with gastrointestinal symptoms tend to have higher elevation in AST and ALT indicating coexistent liver injury ( 34 ). The mechanism behind GI illness is not clearly known but could be due to direct invasion of virus via ACE2 receptor in the intestinal mucosa. This can be supported by the fact that viral RNA can be detected in stool samples of COVID-19 patients which may also hint toward possible fecal-oral transmission ( 35 ). Liver dysfunction is likely secondary to the use of hepatotoxic drugs, hypoxia induced liver injury, systemic inflammation, and multi organ failure ( 36 ).

Renal manifestation in patients with COVID-19 can occur due to direct invasion of podocytes and proximal tubular cells by SARS-CoV-2 virus, secondary endothelial dysfunction causing effacement of foot process with vacuolation and detachment of podocytes, and acute proximal tubular dysfunction ( 37 ). Furthermore, hypoxia, cytokine storm, rhabdomyolysis, nephrotoxic drugs, and overlying infections can all exacerbate renal injury ( 38 ). Based on initial reports, prevalence of Acute Kidney Injury (AKI) among COVID-19 hospitalized patients range from 0.5 to 29%. In a cohort of 701 patients, proteinuria (43.9%), hematuria (26.7%), elevated creatinine (14.4%), elevated blood urea nitrogen (13.1%), and low glomerular filtration rate (≤ 60 ml/min/1.73 m 2 ) (13.1%) were present at the time of hospital admission with 5.1% developing AKI during the illness. AKI was more prevalent among those with baseline renal impairment ( 39 ). In another large cohort of 5,449 patients, 36.6% had AKI with prevalence higher among mechanically ventilated patients compared to non-ventilated patients (89.7 vs. 21.7%) ( 40 ). Patients developing renal impairment are prone to have higher mortality within the hospital. Another point to highlight is the presentation of COVID-19 in renal transplant recipients. Due to immunosuppression, these patients are likely to have low fever at presentation with swift clinical decline and requirement for mechanical ventilation with high mortality as compared to the general population ( 41 ).

Neurological

Most patients with COVID-19 develop neurological symptoms along with respiratory symptoms during the course of illness; however, several case reports in review of literature document patient presentation of neurological dysfunction without typical symptoms of fever, cough, and difficulty breathing ( 42 ). There is a 2.5-fold enhanced risk of severe illness and increased death in patients with a history of previous stroke with similar findings among those with Parkinson's diseases. The prevalence of neurological features ranges from 6 to 36% along with hypoxic ischemic encephalopathy up to 20% in some series of patients ( 43 ). Neurological symptoms tend to occur early in the course of illness (median 1–2 days) with most common neurological features being headache, confusion, delirium, anosmia or hyposmia, dysgeusia or ageusia, altered mental status, ataxia, and seizures ( 44 ). Among patients admitted with COVID-19, the prevalence of ischemic stroke ranges from 2.5 to 5% despite receiving prophylaxis for venous thromboembolism. Patients prone to have established cardiovascular risk factors are likely to have a more severe diseases ( 43 ). Other presentations include viral encephalitis, acute necrotizing encephalopathy (ANE), infectious toxic encephalopathy, meningitis, Guillain Barre Syndrome (GBS), Miller Fisher syndrome, and polyneuritis cranialis with GBS being the first feature of COVID-19 in few cases ( 42 , 43 , 45 ). In COVID-19 patients, CNS features are possibly due to direct invasion of neurons and glial cells by SARS-CoV-2 as well as by endothelial dysfunction of blood brain barrier (BBB). Virus can gain access to CNS via hematogenous spread or retrograde movement across the olfactory bulb. The virus can be detected in CSF by RT-PCR and on brain parenchyma during autopsy. The fact that most patients develop anosmia or hyposmia during illness support this theory ( 45 ). After entry, the virus can cause reactive gliosis with activation of the inflammatory cascade. The combination of systemic inflammation, cytokine storm, and coagulation dysfunction can impair BBB function and alter brain equilibrium causing neuronal death ( 42 ).

Ocular manifestations can vary from conjunctival injection to frank conjunctivitis. In a Chinese cohort of 38 patients, 31.6% had ocular symptoms consisting primarily of conjunctivitis while conjunctival hyperemia, foreign body sensation in eye, chemosis, tearing or epiphora were more common among severe COVID-19 patients. Among them SARS-CoV-2 can be demonstrated in conjunctival as well as nasopharyngeal swab in 5.2% of patients, indicating a potential route for viral transmission ( 46 ). Conjunctivitis or tearing can be the initial presenting symptoms of COVID-19. Despite this fact, there is no documented case of severe ocular features relating to COVID-19.

Similar to other viral infections, SARS-CoV-2 can also produce varied dermatological features. A study of 88 patients from Italy showed that about 20.4% had some form of skin manifestations with 44.4% developing features at onset and duration of the disease progression ( 47 ). Maculopapular exanthem (36.1%) was identified as most common dermatological features followed by papulovesicular rash (34.7%), painful acral red purple papules (15.3%), urticaria (9.7%), livedo reticularis (2.8%), and petechiae (1.4%) ( 48 ). A study of 375 COVID-19 cases in Spain identified five different patterns of cutaneous manifestations in patients: acral areas of erythema with vesicles or pustules (pseudo-chilblain) (19%), other vesicular eruptions (9%), urticarial lesions (19%), maculopapular eruptions (47%), and livedo or necrosis (6%) ( 49 ). Majority of patients had lesions on the trunk with some experiencing lesions on hands and feet. There are case reports of COVID-19 associated with erythema multiforme and Kawasaki Disease in children ( 50 , 51 ). Pathogenesis behind skin involvement remains unclear with some features explained by small vessel vasculitis, thrombotic events like DIC, hyaline thrombus formation, acral ischemia, or the direct effect of the virus like other viral illnesses ( 52 ).

Musculoskeletal

The initial report from China revealed 14.8% of patients had myalgia or arthralgia among 55,924 COVID-19 patients. A review article reports that of 12,046 patients, fatigue was identified in 25.6% and myalgia and/or arthralgia in 15.5% with most patients reporting symptoms from the start of illness ( 53 ). There are reports suggesting myositis and rhabdomyolysis with markedly elevated creatinine kinase can occur during COVID-19 illness especially in patients with severe diseases and multi organ failure. Additionally, in some patients, rhabdomyolysis has been documented as the initial presentation of COVID-19 illness without typical respiratory symptoms ( 54 , 55 ). A case series of four patients developing acute arthritis during hospital admission for COVID-19 has been reported with exacerbation of crystal arthropathy (gout and calcium pyrophosphate diseases) but negative for SARS-CoV-2 RT-PCR in synovial fluid ( 56 ). Treatment with steroids and colchicine was used in all four cases. An important consideration to note was that all four patients developed arthritis despite previous treatment with immunomodulatory therapy (hydroxychloroquine, tocilizumab, and pulse methylprednisolone).

Hematological

As stated, COVID-19 is a systemic disease inducing systemic inflammation and occasionally cytokine storm. This can significantly impact the process of hematopoiesis and hemostasis. During early disease, normal or decreased leukocyte and lymphocyte counts were documented with marked lymphopenia as the diseases progressed, especially in those with cytokine storms and severe disease. In a study of 1,099 patients, lymphopenia, thrombocytopenia, and leukopenia were present in 83.2, 36.2, and 33.7%, respectively, with findings more marked in those with severe diseases ( 18 ). Leukocytosis in COVID-19 patients might suggest a bacterial infection or a superinfection with leukocytosis found more commonly in severe cases (11.4%) as compared to mild and moderate cases (4.8%) ( 18 ). Similarly, thrombocytopenia has been found to be more common (57.7%) in severe cases in contrast to mild and moderate cases (31.6%) ( 18 ). Lymphopenia was also linked with an increased necessity for ICU admission and the risk of ARDS. Thrombocytosis with elevated platelet to lymphocyte ratio may indicate a more marked cytokine storm ( 57 ).

Also, coagulation abnormality can manifest in the form of thrombocytopenia, prolonged prothrombin time (PT), low serum fibrinogen level, and raised D-dimer suggesting Disseminated Intravascular Coagulation (DIC) with these changes more marked in those with severe diseases ( 58 ). Raised lactate dehydrogenase (LDH) and serum ferritin were also present and correlated with the degree of systemic inflammation. In a study of 426 COVID-19 patients, C-Reactive Protein (CRP) was noted to be increased in 75–93% of patients, more commonly in patients with severe disease. Serum procalcitonin levels might not be altered at admission, but progressive increase in its value can suggest a worsening prognosis. Severe disease is linked to increased ALT, bilirubin, serum urea, creatinine, and lowered serum albumin ( 59 ). A study of 1,426 patients showed that Interleukin-6 (IL-6) were raised more in patients with severe COVID-19 than non-severe COVID-19 with progressive rise indicating an increased risk of mortality. Thus, its levels could be regarded as an important prognostic indicator for the extensive inflammation and cytokine storm in COVID-19 patients ( 60 ). Other plasma cytokines and chemokines like IL1B, IFNγ, IP10, MCP, etc. have also been found to be elevated in patients with COVID-19 both in severe and non-severe diseases. Additionally, GCSF, IP10, IL2, IL7, IL10, MCP1, MIP1A, and TNFα were increased in patients who require ICU admission which indicates that cytokine storm is associated with a severe disease ( 61 ).

Endocrine and Reproductive

From the available literature there is no doubt that diabetes mellitus is an important risk factor for COVID-19 illness and is associated with increased risk of development of severe disease. Additionally, there are case reports of subacute thyroiditis linked to SARS-CoV-2 infection ( 62 , 63 ). Based on the statement released from European Society of Endocrinology, patients with primary adrenal failure and congenital adrenal hyperplasia may have theoretically increased susceptibility to infection with higher risk of complications and ultimately mortality but there is no current evidence to support this ( 64 ). The dose of steroids may need to be doubled if there is a clinical suspicion of infection in these patients.

Several claims have been made regarding the impact of COVID-19 on male reproductive function, hypothesizing that COVID-19 can cause potential testicular damage either by binding directly to testicular ACE2 receptors, which are highly expressed in the testicles or by damaging the testis indirectly by exciting local immune system ( 65 ). A study comparing 81 male COVID-19 patients with 100 age matched healthy adults highlighted the presence of low testosterone levels, high levels of luteinizing hormone (LH), low testosterone/LH ratios, low Follicle stimulating hormone (FSH) to LH ratio, and raised serum prolactin. This may suggest a potential COVID-19 testicular damage affecting the Leydig cells in the testis ( 66 ). COVID-19 infected male patients may have reduced sperm count and decreased motility leading to diminished male fertility for 3 months post-infection ( 67 ).

Clinical Presentation in Specific Population

In children.

A case series of 72,314 cases published by the Chinese Center for Disease Control and Prevention reported that 0.9% of the total patients were between 0 and 9 years of age, and 1.2% of the total patients were between 10 and 19 years of age ( 68 ). The most common symptoms found in children are fever, (59%), cough (46%), few cases (12%) of gastrointestinal symptoms, and some cases (26%) showed no specific symptoms initially with patchy consolidation and ground glass opacities in CT chest findings ( 69 ). Chilblain-like acral eruptions, purpuric, and erythema multiforme-like lesions have been found to be more common in children and young adult patients mainly with asymptomatic or mild disease ( 70 ). Lymphopenia in children is relatively less common which is in direct contrast in cases of SARS in children where lymphopenia was more commonly noted ( 69 ).

Multisystem inflammatory syndrome (MIS) is another feared complication of Covid-19 seen in children. Abrams et al. systematically summarized the clinical evidence of 8 studies reporting MIS in 440 children. The median age of patients ranged from 7.3 to 10 years with 59% of all patients being male. The greatest proportion of patients had gastrointestinal symptoms (87%) followed by mucocutaneous symptoms (73%) and cardiovascular symptoms (71%) while fewer patients reported respiratory (47%), neurologic (22%), and musculoskeletal (21%) symptoms. Ferritin and d-dimer were elevated in 50% of patients, and C-reactive protein, interleukin-6, and fibrinogen were elevated in at least 75% of patients. Additionally, 100% of children with cardiovascular involvement reported elevated cardiac-damage markers such as Troponin. Although respiratory manifestation is most frequently expressed in adults, children with MIS exhibited less pulmonary symptoms and more of the other manifestations ( 71 ).

In Pregnant Women

The most common symptoms reported in pregnant women are fever (61.96%), cough (38.04%), malaise (30.49%), myalgia (21.43%), sore throat (12%), and dyspnea (12.05%). Other symptoms found in pregnant women are diarrhea and nasal congestion ( 72 ). In a systematic review including 92 patients, 67.4% manifested diseases at presentation with 31.7% having negative RT-PCR though they had features of viral pneumonia. Only one patient required admission to intensive care and 0% mortality. Fetal outcomes were reported as: 63.8% preterm delivery, 61.1% fetal distress, 80% Cesarean section delivery, 76.92% neonatal intensive care admission, 42.8% low birth weight, and 66.67% had lymphopenia ( 72 ). There was no evidence of vertical transmission. A study of 41 pregnant women with COVID-19 showed that consolidation was more commonly found in CT of pregnant women in contrast to ground-glass opacities in CT of non-pregnant adults ( 73 ). WHO also recommends encouraging lactating mothers with confirmed or suspected COVID-19 to begin or continue breastfeeding including 24-h rooming in, skin to skin contact, and kangaroo mother care especially in immediate postnatal period ( 74 ). On July 14th, 2020, Vivanti et al. published the first case of transplacental transmission of COVID-19 from a 23-years-old pregnant woman to her baby ( 75 ). Thereafter, more studies reported the possibility of the vertical transmission of COVID-19. In this context, Kotlayer et al. published a systematic review of 38 studies. Out of 936 neonates from COVID-19 mothers, 27 tested positive for the virus indicating a pooled proportion of 3.2% (2.2–4.3) for vertical transmission ( 7 ).

In Immuno-Compromised Population

Due to their impaired immune response, it is not surprising that immunocompromised patients with COVID-19 infection might be at greater risk of developing severe forms of the disease and co-infections in comparison to normal populations. Nevertheless, recent studies showed the association between cytokine storm syndrome and the overreaction of the immune system with COVID-19 raising the possibility that immunodeficient states might alleviate the overexpression of the host immune system and thereby prevent deadly forms of the disease ( 76 ). After the RECOVERY trial ( 77 ) that showed the efficacy of dexamethasone in lowering the mortality in severe forms of the disease, many questions were raised regarding whether immunocompromised patients have a greater or lower risk of developing severe forms of the disease. In order to address these questions, Minotti et al. recently published a systematic review that included 16 studies with 110 patients presenting mostly with cancer along with transplantation and immunodeficiency. Out of the 110 patients, 72 (65.5%) recovered without being admitted to the intensive care unit while 23 (20.9%) died ( 76 ). The authors concluded that immunosuppression in both children and adults seem to have a better disease course in comparison to normal population. One of the limitations of this study is that the conclusion was made only based on qualitative synthesis and no meta-analysis was performed. On the other hand, Gao et al. performed a meta-analysis on 8 relevant studies with 4,007 patients. The study showed that immunosuppression and immunodeficiency were associated with non-statistically significant increased risk of severe COVID-19 disease ( 78 ). Additionally, Mirzaei et al. summarized the clinical evidence of 252 HIV positive patients co-infected with COVID-19. The clinical manifestation did not differ from that of the general population. However, out of the 252 patients, 204 (80.9%) were male. Low CD4 count (<200 cells/mm 3 ) were reported for 23 of 176 patients (13.1%). COVID-19 symptoms were present in 223 patients with the most common symptoms of fever in 165 (74.0%) patients, cough in 130 (58.3%), headache in 44 (19.7%), arthralgia and myalgia in 33 (14.8%), gastrointestinal symptoms in 29 (13.0%) followed by sore throat in 18 (8.1%) patients ( 79 ). The number of deaths accounted for 36 (14.3%). Similar to the general population, immunocompromised, and HIV patients were no different in terms of clinical manifestation or severity. However, the results from these studies should be interpreted with caution and more studies are recommended to establish the link between this particular group of patients with severity of the disease.

Multisystem Involvement in COVID-19

As evident from the discussion above, SARS-CoV-2 can affect multiple organ systems and produce a wide array of clinical presentation of COVID-19. Certain studies conducted in Europe and United States have shown that COVID-19 can also have a multi-systemic presentation in individuals in form of a multi-system inflammatory syndrome (MIS) which has been found in both children and adults and is known as MIS-C and MIS-A, respectively ( 80 – 83 ).

According to a recent CDC report about MIS-A, it was found that only half of the patients with MIS-A had preceding respiratory symptoms of COVID-19 ~2–5 weeks before ( 80 ). The most common clinical signs and symptoms included fever, chest pain, palpitations, diarrhea, abdominal pain, vomiting, skin rash, etc. Nearly all patients had electro-cardiological abnormalities like arrythmias, elevated troponin levels, and electrocardiography evidence of left or right ventricular dysfunction. Even though most patients had minimal respiratory symptoms, chest imaging had features of ground glass opacity and pleural effusion. All patients had signs of elevated laboratory markers of inflammation, coagulation markers, and lymphopenia ( 80 ).

MIS-C can clinically mimic Kawasaki Disease ( 81 ). By the end of July, about 570 cases of MIS-C with COVID-19 were found in the United States ( 81 ). In MIS-C, there is involvement of at least four organ systems, most commonly the gastrointestinal system followed by cardiovascular and dermatological systems ( 81 ). Prominent signs and symptoms found in children with MIS-C were abdominal pain, vomiting, skin rash, diarrhea, hypotension, and conjunctival injection. The majority of the children needed ICU admission due to the development of severe complications including cardiac dysfunction, shock, myocarditis, coronary artery aneurysm, and acute kidney injury ( 81 ).

Association Between Clinical Presentations, COVID-19 Severity and Prognosis

Evaluation of 55,924 laboratory confirmed COVID-19 cases in China, the presence of dyspnea, respiratory rate ≥ 30/min, blood saturation levels ≤ 93%, PaO2/FiO2 ratio ≤ 300, lung infiltrates ≥ 50% of the lung fields between 12 and 48 h were associated with severe COVID-19 infection ( 1 ). Clinical signs suggestive of respiratory failure, septic shock, or multiple organ dysfunction/failure were associated with critical disease and poor prognosis ( 1 ). Individuals at highest risk of severe disease and deaths were patients with age > 80 years and associated co-morbidities such as underlying cardiovascular disease, diabetes, hypertension, chronic respiratory disease, and cancer ( 1 ). Another study done with 418 patients in Catalonia (Spain) showed that dyspnea was an important predictor of severe disease while confusion was an important predictor of death, and the presence of cough was strongly associated with good prognosis ( 84 ). Advanced age, male sex, and obesity were independent markers of poor prognosis while eosinophilia was a marker of less severe disease ( 84 ). The mortality was lower in patients with symptoms of diarrhea, arthromyalgia, headache, and loss of smell and taste sensations while low oxygen saturation, high CRP levels, and higher number of lung quadrants affected on Xray were found to be associated with severe disease and death ( 84 ).

COVID-19 is a viral illness which can cause multi-systemic manifestations. Review of existing literature concludes that SARS-CoV-2 can affect any organ system either directly or indirectly leading to a myriad of clinical presentation. The most commonly affected system is the respiratory system with presenting symptoms of fever, cough, and shortness of breath, etc. Other systems which can be affected in COVID-19 include ENT (sore throat, loss of taste, smell, and sensations, and rhinorrhea), cardiovascular system (chest pain, chest tightness, palpitations, and arrhythmias), gastrointestinal system (anorexia, diarrhea, vomiting, nausea, and abdominal pain), renal (proteinuria, hematuria, and acute kidney injury), neurological (headache, confusion, delirium, and altered mental status), ocular (conjunctival hyperemia, foreign body sensation in the eye, chemosis, and tearing), cutaneous (rash, papules, and urticaria), musculoskeletal system (myalgia and arthralgia), hematological (lymphopenia, thrombocytopenia, leukopenia, elevated inflammatory markers, and elevated coagulation markers), endocrine (low testosterone, low FSH, and high LH) and reproductive system (decreased sperm count and decreased sperm motility). Clinical presentation in specific populations like children, pregnant women, and immunocompromised people may vary which emphasizes the importance of further investigation in order to avoid late diagnosis of COVID-19. Severe multi-systemic involvement in COVID-19 in the form of MIS-C and MIS-A can cause significant morbidity and mortality if undiagnosed. The clinical presentations of respiratory failure, acute kidney injury, septic shock, cardiovascular arrest is associated with severe COVID-19 disease and can result in poor prognosis. In the light of exponentially growing pandemic, every patient presenting to hospital must be tested for SARS-CoV-2 by RT-PCR if resources are available to detect early presentations of diseases even if the features are atypical. Understanding of the various clinical presentations of COVID-19 will help the clinicians in early detection, treatment, and isolation of patients in order to contain the virus and slow down the pandemic.

Author Contributions

All authors have contributed equally to the work, and all agreed to be accountable for the content of the work.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

We would like to thank Ms. Sairah Zia (American University of Caribbean, School of Medicine, Sint Maarten), a native speaker of English, for proofreading the manuscript.

Abbreviations

ACC/AHA/HFSA, American College of Cardiology/American Heart Association/Heart Failure Society of America; IL1B, Interleukin 1B; IFNγ, Interferon Gamma; IP10, Interferon-inducible Protein 10; MCP1, Monocyte Chemoattractant Protein 1; GCSF, Granulocyte Colony Stimulating Factor; IL2, Interleukin 2; IL7, Interleukin 7; IL10, Interleukin 10; MIP1A, Macrophage Inflammatory Protein-1 alpha; TNFα, Tumor Necrosis Factor alpha.

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Keywords: SARS-CoV-2, Covid-19, symptomatology, clinical presentation, signs and symptoms, clinical features, coronavirus

Citation: Mehta OP, Bhandari P, Raut A, Kacimi SEO and Huy NT (2021) Coronavirus Disease (COVID-19): Comprehensive Review of Clinical Presentation. Front. Public Health 8:582932. doi: 10.3389/fpubh.2020.582932

Received: 13 July 2020; Accepted: 15 December 2020; Published: 15 January 2021.

Reviewed by:

Copyright © 2021 Mehta, Bhandari, Raut, Kacimi and Huy. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Nguyen Tien Huy, tienhuy@nagasaki-u.ac.jp

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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COVID-19 Infographics

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COVID-19 has been around for a year now, so it's likely that people would need to provide some statistics about its evolution. For that, you'll need charts, infographics... and that's what you'll find in this template! The slides feature backgrounds with gradients and many layouts contain editable graphs. You can try integrating these designs into our COVID-19 presentation template, as both have been devised to work well together. This is the vaccine against boring slideshows!

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