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COVID-19

(Coronavirus Disease 2019; COVID)

By

Brenda L. Tesini

, MD, University of Rochester School of Medicine and Dentistry

Medically Reviewed Aug 2022 | Modified Sep 2022
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COVID-19 is an acute, sometimes severe, respiratory illness caused by the novel coronavirus SARS-CoV-2. Prevention is by vaccination, infection control precautions (eg, face masks, handwashing, social distancing, isolation of infected individuals). Diagnosis is by antigen or PCR (polymerase chain reaction) testing of upper or lower respiratory secretions. Treatment is with supportive care, antiviral drugs, monoclonal antibodies, or corticosteroids.

COVID-19 was first reported in late 2019 in Wuhan, China and spread extensively worldwide. It is caused by SARS-CoV-2, a coronavirus discovered in 2019. SARS-CoV-2 infection causes a spectrum of severity of disease, from asymptomatic to acute respiratory failure and death. Risk factors for severe disease include older age, immunocompromise, comorbidities (eg, diabetes, chronic kidney disease), and pregnancy. Vaccines COVID-19 Vaccine COVID-19 vaccines provide protection against COVID-19, the disease caused by infection with the SARS-CoV-2 virus. Vaccination is the most effective strategy to prevent severe illness and death... read more have shown to be somewhat effective in preventing transmission and very effective in preventing severe disease and mortality.

For current information on the number of cases and fatalities, see the Centers for Disease Control and Prevention (CDC): COVID Data Tracker and the WHO Coronavirus (COVID-19) Dashboard.

Transmission of COVID-19

The SARS-CoV-2 virus spreads by close person-to-person contact, mainly via respiratory droplets produced when an infected person coughs, sneezes, sings, exercises, or talks. The spread occurs through large respiratory droplets that can travel short distances and land directly on mucosal surfaces or through small respiratory particle aerosols that can linger in air for several hours and travel longer distances (> 6 feet) before being inhaled. Spread of the virus could also occur via contact with surfaces contaminated (fomites) by respiratory secretions, if a person touches a contaminated surface and then touches a mucous membrane on the face (eyes, nose, mouth).

The SARS-CoV-2 virus spreads easily between people. The risk of transmission is directly related to the amount of virus to which a person is exposed. In general, the closer and longer the interaction with an infected person, the higher the risk of virus spread. Both asymptomatic and symptomatic patients can transmit the virus, making it difficult to control spread. A symptomatic person is most contagious for the several days before and after the onset of symptoms, at which time the viral load in respiratory secretions is greatest.

Factors such as distance from an infected person, the number of infected people in the room, the duration of time spent with infected people, the size of the air space, aerosol-generating activity (eg, singing, shouting, or exercising), ventilation in the location, and the direction and speed of airflow can contribute to this risk.

Genetic variants of the SARS-CoV-2 virus emerge as it evolves. Variants with the potential for increased transmissibility, more severe disease, or reduced response to available treatments and/or vaccines are tracked as Variants of Concern and are commonly referred to by their WHO-designated Greek alphabet label or their Pango lineage number. A genetic mutation that confer a fitness advantage, namely increased transmissibility, can rapidly replace previously circulating variants. The progression of dominant variants in the US and much of the world includes Alpha, Beta, Delta, and Omicron. The Omicron variant has predominated worldwide since March 2022, with newer and more transmissible Omicron subvariants (eg, BA.4 and BA.5) replacing the original Omicron (B.1.1.529). See also CDC: COVID Data Tracker.

Situations with high risk of transmission include congregate living facilities (eg, elder care or other long-term care facilities, residential schools, prisons, ships) as well as crowded, poorly ventilated environments, such as indoor religious services, gyms, bars, nightclubs, indoor restaurants, and meat-packing facilities. Such situations have a high population density in which maintaining distance and ventilation precautions is difficult. The residents of elder care facilities are also at high risk of severe disease because of age and underlying medical disorders. Large indoor events or private gatherings such as meetings or weddings have also been associated with high transmission rates. These so-called super-spreader events or situations are probably due to a combination of biological, environmental, and behavioral factors.

Social determinants of health (conditions in the places where people are born, live, learn, work, and play) impact a wide range of health risks and outcomes, such as exposure to SARS-CoV-2 infection, severe COVID-19, and death, as well as access to testing, vaccination, and treatment (see CDC: Risk for COVID-19 Infection, Hospitalization, and Death By Race/Ethnicity). In the US, COVID-19 case, hospitalization, and death rates are higher in some racial and ethnic minority groups, including among people who are Black, Hispanic or Latino, American Indian, and Alaska Native.

Quarantine and isolation measures are being applied in an attempt to limit the local, regional, and global spread of this outbreak. (See also CDC: Quarantine and Isolation.)

Symptoms and Signs of COVID-19

The severity and constellation of symptoms vary in people with COVID-19. Some have few to no symptoms, and some become severely ill and die. Symptoms may include

  • Fever

  • Cough

  • Sore throat

  • Congestion or runny nose

  • Shortness of breath or difficulty breathing

  • Chills or repeated shaking with chills

  • New loss of smell or taste

  • Fatigue

  • Muscle pain

  • Headache

  • Nausea or vomiting

  • Diarrhea

The incubation period (ie, time from exposure to symptom onset) ranges from 2 to 14 days, with a median estimated to be only 2 to 4 days for the Omicron variant (1 Symptoms and signs references COVID-19 is an acute, sometimes severe, respiratory illness caused by the novel coronavirus SARS-CoV-2. Prevention is by vaccination, infection control precautions (eg, face masks, handwashing... read more ). Many infected people have no symptoms or mild disease; the likelihood of this varies depending on the SARS-CoV-2 variant and person's risk for severe disease, including COVID immunization status.

Severe disease is characterized by dyspnea, hypoxia, and extensive lung involvement on imaging. This can progress to respiratory failure Overview of Respiratory Failure Acute respiratory failure is a life-threatening impairment of oxygenation, carbon dioxide elimination, or both. Respiratory failure may occur because of impaired gas exchange, decreased ventilation... read more requiring mechanical ventilation, shock, multiorgan failure, and death.

Risk factors for severe disease

The risk of serious disease and death in COVID-19 cases increases in people over age 65, in people who smoke or previously smoked, and in people with other serious medical disorders, such as

  • Cancer

  • Chronic heart, lung, kidney, or liver disease

  • Diabetes

  • Stroke or cerebrovascular disease

  • Immunocompromising conditions

  • HIV infection

  • Tuberculosis

  • Sickle cell disease

  • Thalassemia

  • Dementia

  • Obesity

  • Pregnancy (up to 42 days after pregnancy)

  • Some types of disabilities

  • Substance use disorders

  • Physical inactivity

  • Some mental health disorders such as depression and schizophrenia

Vaccination COVID-19 Vaccine COVID-19 vaccines provide protection against COVID-19, the disease caused by infection with the SARS-CoV-2 virus. Vaccination is the most effective strategy to prevent severe illness and death... read more dramatically lowers the risk of severe illness for all age groups—lower vaccination rates in younger age groups has shifted the age demographic of hospitalized patients (see CDC: COVID Data Tracker).

Complications

A postinfectious inflammatory syndrome termed multisystem inflammatory syndrome in children (MIS-C) has been observed as a rare complication of SARS-CoV-2 infection. It has features similar to Kawasaki disease Kawasaki Disease Kawasaki disease is a vasculitis, sometimes involving the coronary arteries, that tends to occur in infants and children between the ages of 1 year and 8 years. It is characterized by prolonged... read more Kawasaki Disease or toxic shock syndrome Toxic Shock Syndrome (TSS) Toxic shock syndrome is caused by staphylococcal or streptococcal exotoxins. Manifestations include high fever, hypotension, diffuse erythematous rash, and multiple organ dysfunction, which... read more Toxic Shock Syndrome (TSS) . Children with MIS-C most commonly present with fever, tachycardia, signs of systemic inflammation, and multisystem involvement (eg, cardiac, gastrointestinal, renal) at 2 to 6 months following a generally mild or even asymptomatic SARS-CoV-2 infection. Cases meeting the following criteria should be reported to local, state, or territorial health departments as suspected MIS-C: individuals < 21 years old with fever > 24 hours, laboratory evidence of inflammation, signs of severe multisystem (≥ 2 organs) involvement requiring hospitalization, and laboratory or epidemiologic association with recent SARS-CoV-2 infection (2 Symptoms and signs references COVID-19 is an acute, sometimes severe, respiratory illness caused by the novel coronavirus SARS-CoV-2. Prevention is by vaccination, infection control precautions (eg, face masks, handwashing... read more ). Vaccination appears to be highly protective against the development of MIS-C (2 Symptoms and signs references COVID-19 is an acute, sometimes severe, respiratory illness caused by the novel coronavirus SARS-CoV-2. Prevention is by vaccination, infection control precautions (eg, face masks, handwashing... read more ). A similar multisystem inflammatory syndrome in young and middle-aged adults (MIS-A) also has been reported (3 Symptoms and signs references COVID-19 is an acute, sometimes severe, respiratory illness caused by the novel coronavirus SARS-CoV-2. Prevention is by vaccination, infection control precautions (eg, face masks, handwashing... read more ).

Symptom resolution

In most patients, symptoms resolve within about a week. However, some patients begin with mild symptoms, then clinically deteriorate after a week, progressing to severe disease, including ARDS Acute Hypoxemic Respiratory Failure (AHRF, ARDS) Acute hypoxemic respiratory failure is defined as severe hypoxemia (PaO2 (See also Overview of Mechanical Ventilation.) Airspace filling in acute hypoxemic respiratory failure (AHRF) may result... read more Acute Hypoxemic Respiratory Failure (AHRF, ARDS) . Prolonged illness appears to be more common in those with severe disease, but even patients with mild illness may have persistent symptoms, including dyspnea, cough, and malaise that last for weeks or even months. Viral PCR tests in patients may remain positive for at least 3 months regardless of symptoms. However, even patients with lingering symptoms are generally not considered infectious, as virus is rarely able to be cultured from the upper respiratory tract of patients after 10 days of illness.

COVID-19 may also be associated with long-term sequelae following acute illness (4 Symptoms and signs references COVID-19 is an acute, sometimes severe, respiratory illness caused by the novel coronavirus SARS-CoV-2. Prevention is by vaccination, infection control precautions (eg, face masks, handwashing... read more ), and symptoms can linger for months. This has been referred to by many names, including long COVID, long-haul COVID, and post-acute COVID-19 syndrome or condition, and is estimated to impact 25 to 50% of all patients in some US surveys. Fatigue, weakness, pain, myalgias, dyspnea, and cognitive dysfunction are commonly reported. Risk factors for long-term sequelae may include more severe disease presentation, older age, female sex, and pre-existing lung disease. An international case definition has recently been established to aid in the diagnosis and further investigation of this condition (5 Symptoms and signs references COVID-19 is an acute, sometimes severe, respiratory illness caused by the novel coronavirus SARS-CoV-2. Prevention is by vaccination, infection control precautions (eg, face masks, handwashing... read more ).

Symptoms and signs references

  • 1. Jansen L, Tegomoh B, Lange K, et al: Investigation of a SARS-CoV-2 B.1.1.529 (Omicron) variant cluster - Nebraska, November-December 2021. MMWR Morb Mortal Wkly Rep 70(5152):1782-2784, 2021. doi: 10.15585/mmwr.mm705152e3

  • 2. Miller AD, Yousaf AR, Bornstein E, et al: Multisystem inflammatory syndrome in children (MIS-C) during SARS-CoV-2 Delta and Omicron variant circulation - United States, July 2021-January 2022. Clin Infect Dis Jun 10;ciac471, 2022. doi: 10.1093/cid/ciac471

  • 3. Morris SB, Schwartz NG, Patel P, et al: Case series of multisystem inflammatory syndrome in adults associated with SARS-CoV-2 infection — United Kingdom and United States, March–August 2020. MMWR 69:1450–1456, 2020. doi: 10.15585/mmwr.mm6940e1

  • 4. Nalbandian A, Sehgal K, Gupta A, et al: Post-acute COVID-19 syndrome. Nat Med 27(4):601-615, 2021. doi: 10.1038/s41591-021-01283-z. Epub 2021 Mar 22. PMID: 33753937.

  • 5. Soriano JB, Murthy S, Marshall JC, et al: A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis 22(4):e102-e107, 2022. doi: 10.1016/S1473-3099(21)00703-9. Epub 2021 Dec 21. PMID: 34951953; PMCID: PMC8691845.

Diagnosis of COVID-19

  • Real-time reverse transcriptase–polymerase chain reaction (RT-PCR) or other nucleic acid amplification test (NAAT) of upper and lower respiratory secretions

  • Antigen testing of upper respiratory secretions

The following people should be tested for COVID-19:

People who took part in activities that put them at higher risk for COVID-19, such as attending large social gatherings or being in crowded indoor settings without correct and consistent masking, may also want to be tested.

Diagnostic testing for COVID-19 is available through laboratories and public testing sites and can also be done at home. There are two main types of diagnostic COVID-19 tests: real-time reverse transcriptase–polymerase chain reaction (RT-PCR) (or other nucleic acid amplification test [NAAT]) and antigen tests. The choice of diagnostic test and its interpretation should be influenced by the likelihood of the person having COVID-19 based on the prevalence of SARS-CoV-2 in the population and the presence of COVID-19 symptoms, signs, or close contact with a known case of COVID-19.

RT-PCR has the highest analytical sensitivity and specificity and is the gold standard diagnostic test for COVID-19. Other NAAT platforms are generally slightly less sensitive than RT-PCR with equivalent specificity (see CDC: Nucleic Acid Amplification Tests). Positive viral PCR tests, however, do not always indicate active infection. They can detect nonviable viral nucleic acid fragments and may remain positive for at least 3 months after initial diagnosis regardless of symptoms.

Point-of-care and home-based antigen testing can provide rapid results (see CDC: Guidance for Antigen Testing for SARS-CoV-2 for Healthcare Providers Testing Individuals in the Community). This can be an important measure to identify asymptomatic cases and interrupt SARS-CoV-2 transmission. Point-of-care or home-based antigen detection tests are less sensitive than NAATs, particularly at the onset of infection when viral load may be lower. The sensitivity of these tests compared to PCR tests vary by manufacturer and time course of infection, with ranges reported from 40 to 90% (1-4 Diagnosis references COVID-19 is an acute, sometimes severe, respiratory illness caused by the novel coronavirus SARS-CoV-2. Prevention is by vaccination, infection control precautions (eg, face masks, handwashing... read more ). Therefore, it may be necessary to confirm some antigen test results (eg, a negative test in a person with symptoms) with an RT-PCR or other NAAT. Many antigen-detection test kits also recommend repeating the test serially over several days to increase the likelihood of detecting infection. Some tests may not detect the Omicron variant or other emerging variants (see FDA: SARS-CoV-2 Viral Mutations: Impact on COVID-19 Tests). Antigen tests are less likely to stay positive following resolution of infection since they only detect higher viral loads. However, other factors in addition to viral load can influence infectivity; therefore antigen test results do not necessarily correlate with infectiousness.

Acceptable specimens for COVID-19 diagnostic testing include nasopharyngeal, oropharyngeal, nasal mid-turbinate, anterior nares, and saliva. Refer to the accepting laboratory's collection instructions or test kit package insert instructions, because not all testing platforms and laboratories may be able to test all specimen types. These may be collected by a health care practitioner or self-collected, with the exception of nasopharyngeal specimens, which should only be collected by an appropriately trained and credentialed health care practitioner.

For nasopharyngeal and oropharyngeal specimens, use only synthetic fiber swabs with plastic or wire shafts. Do not use calcium alginate swabs or swabs with wooden shafts, as they may contain substances that inactivate some viruses and inhibit PCR testing. The swabs should be placed immediately into a sterile transport tube containing 2 to 3 mL of either viral transport medium, Amies transport medium, or sterile saline, unless using a test designed to analyze the specimen directly, such as a point-of-care test. Maintain proper infection control when collecting specimens.

For biosafety reasons, local institutions and laboratories should not attempt to isolate the virus in cell culture.

Positive test results done in a laboratory or health care setting are reported to local and state health departments. Some local health departments also have mechanisms for reporting positive at home test results.

Serologic, or antibody, testing should not be used to diagnose acute COVID-19 illness, because antibodies most commonly become detectable only 1 to 3 weeks after symptom onset. Antibody tests are available that target the SARS-CoV-2 nucleocapsid antigen, spike antigen, and the receptor binding domain of the spike antigen. Tests that detect antibody to the nucleocapsid protein are recommended to evaluate for evidence of prior infection in vaccinated persons as that antigen is not included in the vaccine. Quantitative and semi-quantitative antibody assays are available, but there is currently no accepted correlate of immunity, and testing is not recommended to determine immune response to vaccination or infection (see CDC: Interim Guidelines for COVID-19 Antibody Testing).

Evaluating symptomatic patients

Routine laboratory findings for those with more severe disease include lymphopenia as well as less specific findings of elevated aminotransaminase (ALT, AST) levels, elevated lactate dehydrogenase (LDH) levels, D-dimer, ferritin, and elevated inflammatory markers such as C-reactive protein.

Patients with dyspnea or other concerning symptoms should be referred for in-person medical evaluation, including oxygen saturation measurement, and followed up with for signs of clinical deterioration.

Chest imaging findings can be normal with mild disease and increase with increasing severity of the illness. Typical findings are consistent with viral pneumonia and include ground-glass opacities and consolidation on either chest x-ray or chest CT. Chest imaging is not recommended as a routine screening tool for COVID-19.

Diagnosis references

  • 1. Drain PK: Rapid diagnostic testing for SARS-CoV-2. N Engl J Med 386(3):264-272, 2022. doi: 10.1056/NEJMcp2117115

  • 2. Ford L, Lee C, Pray IW, et al: Epidemiologic characteristics associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen-based test results, real-time reverse transcription polymerase chain reaction (rRT-PCR) cycle threshold values, subgenomic RNA, and viral culture results from university testing. Clin Infect Dis 73(6):e1348-e1355, 2021. doi: 10.1093/cid/ciab303

  • 3. Wu S, Archuleta S, Lim SM, et al: Serial antigen rapid testing in staff of a large acute hospital. Lancet Infect Dis 22(1):14-15, 2022. doi: 10.1016/S1473-3099(21)00723-4

  • 4. Dinnes J, Sharma P, Berhane S: Rapid, point-of-care antigen tests for diagnosis of SARS-CoV-2 infection. Cochrane Database Sys Rev July 22, 2022. doi: 10.1002/14651858.CD013705.pub3/full

Treatment of COVID-19

  • Supportive care

  • Sometimes, for mild to moderate illness with high-risk of severe disease: nirmatrelvir in combination with ritonavir; remdesivir (short course); neutralizing monoclonal antibodies; molnupiravir

  • For severe illness: remdesivir; dexamethasone; immunomodulators

Treatment of COVID-19 depends on the severity of illness and the likelihood that the patient will develop severe disease. Treatment guidelines are evolving as new data emerge (see National Institutes of Health (NIH) COVID-19 Treatment Guidelines, Infectious Diseases Society of America (IDSA) Guidelines on the Treatment and Management of Patients with COVID-19, and World Health Organization (WHO): Therapeutics and COVID-19: living guideline).

The NIH definitions of severity are as follows:

  • Mild illness: Patients who have any signs and symptoms of COVID-19 (eg, fever, cough, sore throat, malaise, headache, muscle pain) but without shortness of breath, dyspnea, hypoxemia, or abnormal chest imaging

  • Moderate illness: Patients who have evidence of lower respiratory disease by clinical assessment or imaging, and an oxygen saturation (SpO2) ≥ 94% on room air at sea level

  • Severe illness: Patients who have respiratory rate > 30 breaths per minute, SpO2 < 94% on room air at sea level (or, for patients with chronic hypoxemia, a > 3% decrease from baseline), ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) < 300 mmHg, or lung infiltrates > 50%

  • Critical illness: Patients who have respiratory failure, septic shock, and/or multiple organ dysfunction

The effectiveness of particular antiviral drugs and monoclonal antibodies against locally circulating variants is considered when making treatment decisions (see Open Data Portal: database of in vitro therapeutic activity against SARS-CoV-2 variants). Treatment options are listed in order of preference based on currently available data and circulating SARS-CoV-2 variants. Treatment choice should be based on drug availability, infrastructure to administer the drug, and patient-specific factors that include symptom duration, potential drug interactions, and liver and renal impairment. There are no data regarding combination treatments with the currently available therapies; therefore, only 1 drug should be administered.

Supply limits and administration constraints may require clinicians to prioritize patients who are likely to receive the greatest benefit (eg, preventing hospitalization and death). This would include patients who are infected rather than exposed and unvaccinated, incompletely vaccinated, or vaccinated but not expected to mount an adequate immune response due to immunocompromising conditions.

Early treatment for patients with mild to moderate COVID-19 who are high risk for progression to severe illness

These treatments are intended to prevent progression to severe disease in high-risk patients. They are given to patients within a few days of onset of mild to moderate COVID-19 who are ambulatory (or hospitalized for reasons other than COVID-19); treatment options (other than remdesivir) have not been studied in patients hospitalized for COVID-19.

Nirmatrelvir, an oral antiviral drug, given in combination with ritonavir, received Emergency Use Authorization (EUA) from the US Food and Drug Administration (FDA) for treatment of mild to moderate COVID-19 in adults and adolescents (≥ 12 years of age weighing ≥ 40 kilograms) who have positive results of direct SARS-CoV-2 viral testing and who are at high risk for progression to severe COVID-19. The nirmatrelvir/ritonavir combination should be initiated as soon as possible after diagnosis of COVID-19 and within 5 days of symptom onset. The dosage is two 150-mg tablets of nirmatrelvir and one 100-mg tablet of ritonavir taken together orally twice a day for 5 days. This drug treatment is not authorized for use for longer than 5 consecutive days. (See also the FDA EUA Factsheet.)

Nirmatrelvir is a protease inhibitor that cleaves a SARS-CoV-2 protein and therefore inhibits the virus from replicating. Ritonavir is a strong cytochrome P450 (CYP) 3A4 inhibitor and acts as a boosting agent; it slows down the metabolism of nirmatrelvir, causing it to remain in the body for a longer duration at higher concentrations.

The nirmatrelvir/ritonavir combination was studied in a randomized controlled trial of 2,246 nonhospitalized symptomatic adults ≥ 18 years of age with a prespecified risk factor for progression to severe disease or ≥ 60 years of age regardless of prespecified chronic medical conditions. All patients had not received a COVID-19 vaccine, had not been previously infected with COVID-19, and had a laboratory confirmed diagnosis of SARS-CoV-2 infection. The nirmatrelvir/ritonavir combination given at ≤ 5 days after symptom onset reduced the proportion of people with COVID-19-related hospitalization or death from any cause through day 28 compared to placebo by 88% (0.8 vs. 6.3%) (1 Treatment references COVID-19 is an acute, sometimes severe, respiratory illness caused by the novel coronavirus SARS-CoV-2. Prevention is by vaccination, infection control precautions (eg, face masks, handwashing... read more ).

Using the nirmatrelvir/ritonavir combination in people with uncontrolled or undiagnosed HIV-1 infection may lead to HIV-1 drug resistance. The nirmatrelvir/ritonavir combination may cause liver damage, so caution should be exercised in patients with preexisting liver disease, liver enzyme abnormalities, or hepatitis. The drug is not recommended in patients with severe liver.

In patients with moderate renal impairment, which is an estimated creatinine clearance (also called estimated glomerular filtration rate or eGFR) of 30 to 60 mL/minute, the dose is reduced to 150 mg nirmatrelvir (one 150-mg tablet) with 100 mg ritonavir (one 100-mg tablet), with both tablets taken together twice a day for 5 days. Nirmatrelvir/ritonavir combination is not recommended in patients with severe kidney impairment (eGFR < 30 mL/minute).

Return of symptoms has been reported in some patients after use of nirmatrelvir/ritonavir, and PCR and antigen tests for SARS-CoV-2 can become positive again, even in patients who remain asymptomatic. Additional treatment is not currently recommended, but patients should be advised to re-isolate if rebound symptoms or tests occur. (See also CDC: COVID-19 Rebound After Paxlovid Treatment.)

The nirmatrelvir/ritonavir combination drug has a variety of serious known and possible drug interactions; concomitant drugs must be screened for these prior to initiation of treatment. For a list of these drug interactions see the FDA EUA Fact Sheet.

Remdesivir, an intravenous antiviral drug, is used to treat mild to moderate COVID-19 in adults and adolescents (≥ 12 years old and weighing ≥ 40 kilograms) who have positive results of direct SARS-CoV-2 viral testing and who are at high risk for progression to severe COVID-19. It should be initiated as soon as possible and within 7 days of symptom onset. The dose of a 3-day course of remdesivir is 200 mg IV on day 1 and 100 mg IV on days 2 and 3. The course can be extended to 5 days for patients who progress to severe disease.

Remdesivir was studied for this indication in a randomized controlled trial of 562 nonhospitalized patients age ≥ 12 years of age with symptomatic COVID-19 at high risk for progression to severe disease and who had not received a COVID-19 vaccine. Remdesivir given for 3 days and started within 7 days of symptom onset reduced hospitalization or death rates through day 28 compared to placebo by 87% (0.7 vs. 5.3%) (2 Treatment references COVID-19 is an acute, sometimes severe, respiratory illness caused by the novel coronavirus SARS-CoV-2. Prevention is by vaccination, infection control precautions (eg, face masks, handwashing... read more ).

Bebtelovimab is a neutralizing anti-SARS-CoV-2 monoclonal antibody (mAb) therapy that has received FDA EUA for the treatment of mild to moderate COVID-19 in adults and adolescents (≥ 12 years of age weighing ≥ 40 kilograms) who have positive results of direct SARS-CoV-2 viral testing and who are at high risk for progression to severe COVID-19. Of the FDA-approved monoclonal antibodies, only bebtelovimab efficiently neutralizes the new circulating Omicron subvariants. Bebtelovimab should be used as an alternative therapy ONLY when the nirmatrelvir/ritonavir combination and remdesivir are not available, not feasible to use, or clinically inappropriate. Treatment should be initiated as soon as possible and within 7 days of symptom onset.

Molnupiravir, an oral antiviral drug, is a nucleoside analogue that works by introducing errors into the SARS-CoV-2 viral genome, which inhibits viral replication. It has received FDA EUA for treatment of mild to moderate COVID-19 in nonhospitalized adults ≥ 18 years of age who have positive results of direct SARS-CoV-2 viral testing and who are at high risk for progression to severe disease, including hospitalization or death, and for whom alternative COVID-19 treatment options authorized by the FDA are not accessible or clinically appropriate. Molnupiravir should be initiated as soon as possible after diagnosis of COVID-19 and within 5 days of symptom onset. Molnupiravir is administered as four 200-mg capsules taken orally every 12 hours for 5 days. It is not authorized for use for longer than 5 consecutive days. (See also the FDA EUA Factsheet for Molnupiravir.)

Molnupiravir may have an effect on the emergence of new SARS-CoV-2 variants based on a theoretical concern; however, the risk is believed to be low based on available genotoxicity data and the limited 5-day treatment course. Molnupiravir is not authorized for use in patients < 18 years of age because it may affect bone and cartilage growth. Molnupiravir is not recommended for use during pregnancy because animal reproduction studies suggested that molnupiravir may cause fetal harm when administered to pregnant patients. Females of childbearing potential are advised to use a reliable method of birth control correctly and consistently during treatment with molnupiravir and for 4 days after the final dose. Males of reproductive potential who are sexually active with females of childbearing potential are advised to use a reliable method of birth control correctly and consistently during treatment with molnupiravir and for at least 3 months after the final dose.

Molnupiravir was studied in a randomized, double-blind, placebo-controlled clinical trial of 1433 nonhospitalized patients ≥ 18 years of age with mild to moderate COVID-19 at high risk for progression to severe COVID-19 and/or hospitalization and who had not received a COVID-19 vaccine. Molnupiravir given for 5 days and started within 5 days of symptom onset reduced hospitalization or death rates through day 29 compared to placebo (6.8 vs. 9.7%) (3 Treatment references COVID-19 is an acute, sometimes severe, respiratory illness caused by the novel coronavirus SARS-CoV-2. Prevention is by vaccination, infection control precautions (eg, face masks, handwashing... read more ).

Bamlanivimab plus etesevimab, casirivimab plus imdevimab, and sotrovimab are neutralizing anti-SARS-CoV-2 monoclonal antibody (mAb) therapies. The FDA recommended (April 22, 2022) against their use in treatment of COVID-19 because Omicron has become the dominant variant in the United States and the new circulating Omicron subvariants are resistant to their neutralizing activity (see NIH: Anti-SARS-CoV-2 Monoclonal Antibodies).

Treatment for patients with severe COVID-19

Recommended treatment options for severe infection include the antiviral drug remdesivir, the corticosteroid dexamethasone, and additional immunomodulatory drugs such as baricitinib, tocilizumab, and sarilumab. These may be used in combination, and treatment decisions should take into account the patient's phase of illness, often characterized by the degree of hypoxia and respiratory support.

Antiviral drugs are more likely to provide benefit earlier in the course when illness is a result of active viral replication, whereas anti-inflammatory and immunomodulatory therapies are better suited for later in the course when the host inflammatory response and immune dysregulation are driving the disease state. (Also see NIH: Therapeutic Management of Hospitalized Adults With COVID-19.)

For patients requiring supplemental oxygen but not additional respiratory support, treatment options include

  • Remdesivir alone

  • Dexamethasone alone

  • Remdesivir plus dexamethasone

The antiviral drug remdesivir is used to treat adult and pediatric patients ≥ 28 days of age and weighing ≥ 3 kg who require hospitalization for COVID-19. The recommended dosage for adults and pediatric patients weighing ≥ 40 kg is a single loading dose of 200 mg on Day 1 via intravenous infusion followed by once-a-day maintenance doses of 100 mg from Day 2 via intravenous infusion. The recommended dosage for pediatric patients ≥ 28 days of age and weighing 3 kg to less than 40 kg is a single loading dose of 5 mg/kg on Day 1 via intravenous infusion followed by once-a-day maintenance doses of 2.5 mg/kg from Day 2 via intravenous infusion. The recommended treatment duration is 5 days but is approved for use up to 10 days in patients who require invasive mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO). Benefits of antiviral treatment in this group though are inconclusive.

Overall, studies of remdesivir support its use early in infection (prior to days 7 to 10) when active viral replication is more likely to be contributing to illness. Remdesivir can also be considered in patients who are hospitalized but not requiring supplemental oxygen, although data are lacking in this population. Remdesivir is not recommended for patients with an eGFR < 30 mL/minute. Renal function should be monitored before and during remdesivir treatment. (See also the NIH treatment guidelines on remdesivir.)

The corticosteroid dexamethasone (at a dosage of 6 mg once per day for up to 10 days or until hospital discharge, whichever comes first) is generally recommended in patients with COVID-19 who require supplemental oxygen, but its use is not recommended in patients who do not require supplemental oxygen. Dexamethasone showed a survival benefit for those requiring supplemental oxygen or mechanical ventilation in the RECOVERY trial (7 Treatment references COVID-19 is an acute, sometimes severe, respiratory illness caused by the novel coronavirus SARS-CoV-2. Prevention is by vaccination, infection control precautions (eg, face masks, handwashing... read more ). Its benefit is likely to be greatest in patients whose illness is due to the inflammatory response from infection. If dexamethasone is not available, other corticosteroids (eg, prednisone, methylprednisolone, hydrocortisone) may be used.

The combination of remdesivir and dexamethasone is commonly used in hospitalized patients requiring supplemental oxygen within the first 10 days of illness when both viral replication and host inflammation may be contributing to the clinical presentation.

For patients requiring noninvasive ventilation (including high flow oxygen delivery systems), treatment options include

  • Dexamethasone is recommended for all patients.

  • Remdesivir may be added with particular consideration for patients within 7 to 10 days of symptom onset.

  • Additional immunomodulatory drugs should be considered, particularly for patients with rapid deterioration or signs of systemic inflammation.

Additional immunomodulators include the JAK inhibitor baricitinib (or tofacitinib if unavailable) or the IL-6 inhibitor tocilizumab (or sarilumab if unavailable). These recommendations are based on subgroup analyses of numerous randomized (COV-BARRIER, ACTT-2) and open label (REMAP-CAP, RECOVERY) clinical trials that showed survival benefit with addition of one of these drugs in patients requiring this level of respiratory support. These drugs are potent immunosuppressants, and the potential benefit should be weighed against the additional immunosuppressive risk in patients with suspicion of a concomitant serious bacterial or fungal infection or at high risk for opportunistic infections due to an underlying immunosuppressive condition. See NIH treatment guidelines on immunomodulators for further details regarding appropriate patient selection for these therapies.

For patients requiring mechanical ventilation or ECMO, dexamethasone is recommended for all patients. The addition of tociluzumab should be considered for patients within 24 hours of admission to the intensive care unit (ICU).

Many therapies have been considered and are not currently recommended for the treatment or prevention of COVID-19:

An NIH panel concluded there is insufficient evidence to recommend either for or against the use of ECMO in adults with COVID-19 and refractory hypoxemia (see NIH COVID-19 Treatment Guidelines: Extracorporeal Membrane Oxygenation [May 31, 2022]).

Complications of COVID-19 illness should be treated as they arise. Hospitalized patients with COVID-19 may be at increased risk for thromboembolic events. Guidelines around managing this increased risk are continually evolving as data emerge (see NIH: The COVID-19 Treatment Guidelines Panel's Statement on Anticoagulation in Hospitalized Patients With COVID-19). Currently, therapeutic anticoagulation Anticoagulants All patients with deep venous thrombosis (DVT) are given anticoagulants and in rare cases thrombolytics. A number of anticoagulants are effective for management of deep venous thrombosis (see... read more should be considered in nonpregnant, hospitalized patients requiring supplemental oxygen but not intensive care if they have an elevated D-dimer and no serious bleeding risk. The risk of an adverse event from bleeding outweighs the potential benefit in critically ill patients. Pharmacologic anticoagulation prophylaxis should be considered for all other patients.

Drugs such as angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) therapy should be continued if needed for concomitant medical conditions but not started as treatment for COVID-19. There is no evidence that use of nonsteroidal anti-inflammatory drugs (NSAIDs) is linked to worse outcomes, and either acetaminophen or NSAIDs can be used during the treatment of COVID-19.

Respiratory management of the nonintubated and intubated COVID-19 patient should take into consideration the tendency toward hypoxia. Nonpharmacologic adjunctive measures such as frequent repositioning and ambulation may be helpful. Therapeutic decisions should be made to best manage the patient but also consider the risk of exposure to health care practitioners and best use of resources. Intubation is a time of particular risk of health care practitioner exposure to infectious aerosols and should be done with extreme care.

Treatment references

  • 1. Hammond J, Leister-Tebbe H, Gardner A, et al: Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19. N Engl J Med 386(15):1397-1408, 2022. doi: 10.1056/NEJMoa2118542

  • 2. Gottlieb RL, Vaca CE, Paredes R et al: Early remdesivir to prevent progression to severe covid-19 in outpatients. N Engl J Med 386(4):305-315, 2022. doi: 10.1056/NEJMoa2116846. Epub 2021 Dec 22. PMID: 34937145; PMCID: PMC8757570.

  • 3. Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al: Molnupiravir for oral treatment of Covid-19 in nonhospitalized Patients. N Engl J Med 386(6):509-520, 2022. doi: 10.1056/NEJMoa2116044

  • 4. Beigel JH, Tomashek KM, Dodd LE, et al: Remdesivir for the treatment of Covid-19 - final report. N Engl J Med 383(19):1813-1826, 2020. doi: 10.1056/NEJMoa2007764. Epub 2020 Oct 8. PMID: 32445440; PMCID: PMC7262788.

  • 5. WHO Solidarity Trial Consortium: Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO Solidarity randomised trial and updated meta-analyses. Lancet 399(10339):1941-1953, 2022. doi: 10.1016/S0140-6736(22)00519-0

  • 6. Ader F, Bouscambert-Duchamp M, Hites M, et al: Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial. Lancet Infect Dis 22(2):209-221, 2022. doi: 10.1016/S1473-3099(21)00485-0

  • 7. RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, et al: Dexamethasone in hospitalized patients with Covid-19. N Engl J Med 384(8):693-704, 2021. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595.

  • 8. Janiaud P, Axfors C, Schmitt AM, et al: Association of convalescent plasma treatment with clinical outcomes in patients with COVID-19: A systematic review and meta-analysis. JAMA 325(12);1185-1195, 2021, doi: 10.1001/jama.2021.2747

  • 9. Popp M, Stegemann M, Metzendorf MI, et al: Ivermectin for preventing and treating COVID-19. Cochrane Database Syst Rev. 7(7):CD015017, 2021. doi: 10.1002/14651858.CD015017.pub2

  • 10, Reis G,Silva EASM, Silva DCM, et al: Effect of early treatment with ivermectin among patients with COVID-19. N Engl J Med 386:1721-1731, 2022. doi: 10.1056/NEJMoa2115869

Post–COVID-19 Infection

Viral PCR tests in patients may remain positive for at least 3 months regardless of symptoms. However, even patients with lingering symptoms are generally not considered infectious, as virus is rarely if ever able to be cultured from the upper respiratory tract of patients after 10 days of illness.

Although infection with coronaviruses may confer some degree of immunity to reinfection, the duration and effectiveness of immunity following COVID-19 remain difficult to quantify and depend upon multiple host and viral factors. Neutralizing antibodies are detected in most patients following SARS-COV-2 infection, but the levels of these are more variable than in persons after vaccinations. These likely provide protection against clinically apparent reinfection in most immunocompetent people for at least 3 and up to 6 months, but this time frame may be shorter if a new antigenically distinct variant emerges. Symptoms associated with reinfection tend to be similar to or milder than initial infections. Patients who have had COVID-19 are still recommended to receive all eligible vaccinations to reduce the risk of reinfection. They can do so when clinically recovered from infection and completing the isolation period.

COVID-19 may also be associated with long-term sequelae following acute illness (1 Post–COVID-19 infection references COVID-19 is an acute, sometimes severe, respiratory illness caused by the novel coronavirus SARS-CoV-2. Prevention is by vaccination, infection control precautions (eg, face masks, handwashing... read more ), and symptoms can linger for months. This has been referred to by many names, including long COVID, long-haul COVID, and post-acute COVID-19 syndrome or condition, and is estimated to impact 25 to 50% of all patients in some US surveys. Fatigue, weakness, pain, myalgias, dyspnea, and cognitive dysfunction are commonly reported. Risk factors for long-term sequelae may include more severe disease presentation, older age, female sex, and pre-existing lung disease. An international case definition has recently been established to aid in the diagnosis and further investigation of this condition (2 Post–COVID-19 infection references COVID-19 is an acute, sometimes severe, respiratory illness caused by the novel coronavirus SARS-CoV-2. Prevention is by vaccination, infection control precautions (eg, face masks, handwashing... read more ).

Post–COVID-19 infection references

  • 1. Nalbandian A, Sehgal K, Gupta A, et al: Post-acute COVID-19 syndrome. Nat Med 27(4):601-615, 2021. doi: 10.1038/s41591-021-01283-z. Epub 2021 Mar 22. PMID: 33753937.

  • 2. Soriano JB, Murthy S, Marshall JC, et al: A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis 22(4):e102-e107, 2022. doi: 10.1016/S1473-3099(21)00703-9. Epub 2021 Dec 21. PMID: 34951953; PMCID: PMC8691845.

Prevention of COVID-19

COVID-19 vaccination

Vaccination is the most effective way to prevent severe illness and death from COVID-19, including from the Delta and Omicron variants. In the US in the fall of 2021, unvaccinated people were 78 times more likely to die from COVID-19 than vaccinated people (with booster) (1 Prevention references COVID-19 is an acute, sometimes severe, respiratory illness caused by the novel coronavirus SARS-CoV-2. Prevention is by vaccination, infection control precautions (eg, face masks, handwashing... read more ).

Vaccines available in the US are administered as a primary series of 1, 2, or 3 injections. Protection against infection from a primary series has been shown to decrease over time. To maximize protection against infection, severe disease, and death, booster doses are recommended for people 5 years of age and older (see CDC: COVID-19 Vaccine Boosters).

In the US, the booster dose is a bivalent formulation. The bivalent boosters contain two messenger RNA (mRNA) components of SARS-CoV-2 virus, one of the original strain of SARS-CoV-2 and the other one in common between the BA.4 and BA.5 lineages of the Omicron variant. One bivalent booster dose is given at least 2 months after completing the primary vaccination series or prior non-bivalent booster doses. The CDC has stated that monovalent mRNA COVID-19 vaccines are no longer authorized as booster doses, even if the person had not previously received a monovalent booster dose.

People who have received a booster dose when eligible are considered "up-to-date" on their vaccine series. The efficacy of booster doses was illustrated in a study of 182,122 people in Israel who were ≥ 60 years and who received a second booster dose (4th overall dose) and were matched to compare to people who received only the first booster dose (3rd overall dose) of BNT162b2 demonstrated excellent efficacy of the vaccine for preventing symptomatic disease, hospitalization, and death. In days 7 to 30 after a fourth vaccine dose, there was a 55% reduction in symptomatic COVID-19, a 68% reduction in COVID-19 related hospitalization, and a 74% reduction in COVID-19 related deaths (2 Prevention references COVID-19 is an acute, sometimes severe, respiratory illness caused by the novel coronavirus SARS-CoV-2. Prevention is by vaccination, infection control precautions (eg, face masks, handwashing... read more ).

Multiple COVID-19 vaccines are currently in use worldwide. For more information on global vaccine approvals and clinical trials, see the VIPER (Vaccines, Infectious disease Prevention, and Epidemiology Research) Group COVID-19 Vaccine Development and Approvals Tracker Team's COVID-19 Vaccine Tracker, the UNICEF COVID-19 Vaccine Market Dashboard, and the World Health Organization’s COVID-19 vaccine tracker and landscape.

mRNA vaccines do not contain viral antigen but rather deliver a small, synthetic piece of mRNA that encodes for the desired target antigen (the spike protein). After being taken up by cells of the immune system, the vaccine mRNA degrades after instructing the cell to produce viral antigen. The antigen is then released and triggers the desired immune response to prevent severe infection upon subsequent exposure to the actual virus.

Adenovirus vector vaccines contain a piece of the DNA, or genetic material, that is used to make the distinctive “spike” protein of the SARS-CoV-2 virus, which then triggers the desired immune response.

Protein subunit adjuvanted vaccines contain a recombinant SaRS-COV-2 spike protein along with an adjuvant that triggers the desired immune response. This is a classic vaccine approach that has been used in the US for over 30 years.

Two mRNA vaccines (BNT162b2 and mRNA-1273), one adenovirus vector vaccine (Ad26.COV2.S), and one protein subunit adjuvanted vaccine (NVX-CoV2373) are used in the US (see CDC: COVID-19 Vaccination Clinical & Professional Resources).

In almost all situations, the mRNA vaccines and the protein subunit adjuvanted vaccine are preferred over the adenovirus vector vaccine due to the risk of serious adverse events. There is a plausible causal relationship between the adenovirus vector vaccine and a rare and serious adverse event—blood clots with low platelets (vaccine-induced thrombosis with thrombocytopenia syndrome, or VITTS) (see CDC: Johnson & Johnson’s Janssen COVID-19 Vaccine Overview and Safety).

Exposure prevention

In addition to being vaccinated, people can avoid being exposed to the virus by washing hands frequently, wearing face masks, staying 6 feet away from other people, avoiding poorly ventilated spaces and crowds, and taking other steps recommended by the Centers for Disease Control and Prevention (CDC). People should also have COVID-19 testing if they are exposed to an infected individual or have symptoms. Symptomatic or infected individuals should follow recommendations for isolation.

Areas of sustained transmission vary. The CDC varies its recommendations regarding prevention measures based on COVID-19 Community Levels. Levels can be low, medium, or high and are determined by looking at hospital beds being used, hospital admissions, and the total number of new COVID-19 cases in an area. For areas inside the US, clinicians should consult state or local health departments. The CDC advises that travel increases the chance of getting and spreading COVID-19 and recommends avoiding all cruise ship travel due to the global pandemic; for current information see CDC: Coronavirus Disease Information for Travel.

To help prevent spread of SARS-CoV-2 from suspected cases, health care practitioners should use standard, contact, and airborne precautions with eye protection. Airborne precautions are particularly relevant for patients undergoing aerosol-generating procedures.

Pre-exposure prophylaxis

For select immunocompromised patients, the anti SARS-CoV-2 monoclonal antibodies tixagevimab plus cilgavimab has received FDA EUA for pre-exposure prophylaxis against COVID-19. Use is limited to moderately to severely immunocompromised people aged 12 and older or people for whom COVID-19 vaccination is contraindicated due to severe allergic reaction to COVID-19 vaccine(s). It is not a substitute for vaccination and should not be administered to unvaccinated individuals expected to be able to mount an immune response to vaccination.

Prevention references

  • 1. Johnson AG, Amin AB, Ali AR, et al: COVID-19 incidence and death rates among unvaccinated and fully vaccinated adults with and without booster doses during periods of delta and omicron variant emergence — 25 U.S. Jurisdictions, April 4–December 25, 2021. MMWR Morb Mortal Wkly Rep 71:132–138. 2022. doi: 10.15585/mmwr.mm7104e2

  • 2. Magen O, Waxman JG, Makov-Assif M, et al: Fourth dose of BNT162b2 mRNA Covid-19 vaccine in a nationwide setting. N Engl J Med 386(17):1603-1614, 2022. doi: 10.1056/NEJMoa2201688. Epub 2022 Apr 13. PMID: 35417631; PMCID: PMC9020581.

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