COVID-19 (coronavirus disease 2019)

Last updated: May 12, 2022

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COVID-19 is an acute infectious disease caused by the coronavirus SARS-CoV-2. Transmission most commonly occurs via exposure to respiratory fluids. The incubation period varies between 2–14 days and may be shorter with newer variants. Common presenting symptoms include fatigue, fever, and symptoms of an upper respiratory tract infection; affected individuals may also be asymptomatic. Clinical courses range from asymptomatic infection, to mild with minimal symptoms, to severe with pneumonia and life-threatening complications (e.g., acute respiratory distress syndrome, shock, organ dysfunction). Diagnostic confirmation is made based on COVID-19 testing, which includes nucleic acid amplification testing (e.g., PCR) or antigen testing on a respiratory specimen. Imaging findings are nonspecific, resemble those in other viral respiratory tract infections, and should not be used to confirm the diagnosis of COVID-19. Individuals with mild COVID-19 can typically be managed with supportive care at home. Pharmacotherapy can be considered for outpatients with risk factors for progression to severe COVID-19. Patients with moderate or severe COVID-19 or those with risk factors for severe disease may require hospitalization for oxygen therapy, pharmacotherapy, and antithrombotic therapy. The risk of infection can be reduced through preventive efforts, which include vaccination, public health measures (e.g., social distancing, mask-wearing), and getting tested after close contact with infected individuals.

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  • Incidence and prevalence: Refer to the resources below for up-to-date statistics.
    • Johns Hopkins University & Medicine Coronavirus Resource Center: https://coronavirus.jhu.edu/map.html [1]
    • CDC COVID Data tracker: https://covid.cdc.gov/covid-data-tracker/#datatracker-home [2]
  • Distribution
    • The first cases of COVID-19 were reported in Wuhan, China in December 2019.
    • The World Health Organization (WHO) classified COVID-19 as a pandemic on March 11, 2020.
  • Demographics [2]
    • The number of cases is similar between men and women. [3]
    • Affects people of all ages; serious disease is more likely in individuals ≥ 65 years of age. [4]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [5]

SARS-CoV-2 variants [8][9]

  • Several variants have been detected worldwide.
  • The CDC considers a variant of concern to be one with any of the following:
    • Increased transmission rate
    • Resistance to neutralizing antibodies
    • Reduced vaccine effectiveness
    • Increased illness severity or mortality
    • Decreased ability to be identified through diagnostic testing
    • Decreased susceptibility to treatment
Current SARS-CoV-2 variants of concern (Last updated: February 2022) [8][9]
Variant Pango lineage First detected Features (relative to the orignal strain)
Delta
  • B.1.617.2
  • AY
  • India, Oct. 2020
  • Increased transmissibility and severity
  • Decreased neutralization by antibodies [10]
Omicron
  • B.1.1.529
  • BA
  • South Africa and Botswana, Nov. 2021 [11]
  • Increased transmissibility
  • Decreased severity [12]
  • Decreased neutralization by antibodies [13]
Previous SARS-CoV-2 variants of concern [8]
Variant Pango lineage First detected Features (relative to the original strain)
Alpha
  • B.1.1.7
  • Q
  • United Kingdom, Sep. 2020
  • Increased transmissibility [14]
  • Increased disease severity and mortality [15]
Beta
  • B.1.351
  • South Africa, May 2020
  • Increased transmissibility [16]
  • Decreased neutralization by antibodies [17]
Epsilon
  • B.1.427
  • B.1.429
  • US July 2020 (B.1.429) [18]
Gamma
  • P.1
  • Brazil, Nov. 2020
  • Concern for increased transmissibility [20]
  • Decreased neutralization by antibodies [21]

Transmission [22]

  • The basic reproduction number (R0) of the original strain is estimated to be ∼ 2–3.
  • The R0 is higher in newer variants compared to the original strain.
  • Factors affecting R0 include:
    • Duration of infectiousness: Individuals with COVID-19 are infectious from ∼2–3 days before symptom onset until ∼ 8 days after symptom onset. [23][24]
    • Likelihood of infection spreading between individuals (see “Modes of transmission”)
    • Rate of close contacts between individuals with and without infection
  • Efforts to reduce the contact rate (e.g., social distancing, quarantine) aim to lower the R0

“Flattening the curve”, a reference to the number of new cases depicted on a graph, refers to reducing the number of people infected by each infectious individual. Flattening the curve means that new infections are distributed over a longer period of time.

Modes of transmission [4][25]

  • The primary mode of transmission is exposure to respiratory fluids via either:
    • Inhalation of droplets or aerosol particles
      • The concentration of aerosol particles is highest within 3–6 feet of the infectious source.
      • Small aerosol particles can remain suspended in the air for minutes to hours.
      • The risk of transmission is increased in poorly ventilated areas.
    • Mucous membrane contact with respiratory particles
  • Fomite transmission is possible but unlikely to be a major mode of transmission. [26]
  • Vertical transmission: See “COVID-19: pregnancy and breastfeeding.”

SARS-CoV-2 can be transmitted by asymptomatic individuals.

Viral life cycle [5][27]

ACE2 is expressed in the surface epithelium of the lungs, heart, and other organs. TMPRSS2 is expressed in respiratory epithelium. [5]

Effects

Delta or Omicron variants of COVID-19 often manifest with milder symptoms (e.g., headache, rhinitis, fever, and sore throat) compared to prior strains.

General principles [4]

  • Diagnostic confirmation is based on viral testing for COVID-19.
  • Imaging
    • Should not be used as a screening modality or the sole diagnostic modality for COVID-19
    • May be indicated to assess disease severity and rule out alternative diagnoses
    • See “Approach to imaging in COVID-19” for details.

Collection of specimens [4][39]

Obtain a lower respiratory tract sample if there is clinical concern for COVID-19 pneumonia in an intubated patient with negative upper respiratory tract testing. [4]

COVID-19 tests

COVID-19 tests [4][40]
Virological tests for COVID-19 Serological testing [4]
Nucleic acid amplification testing (NAAT; RT-PCR-based test) Antigen testing
Use
Specimen
  • Serum, plasma, or whole blood
Method
Advantages
  • High sensitivity and specificity for SARS-CoV-2
  • Repeat testing is generally not needed to confirm results.
  • Results available within 15–30 minutes
  • High specificity
  • Lower costs compared to NAATs
  • Widely available and easy to perform
  • Identifies individuals who have acquired antibodies through previous SARS-CoV-2 infection
  • Testing large numbers of people allows for the estimation of population-level exposure
  • Rapid IgM-IgG antibody tests can provide results within a few minutes.
Limitations
  • Less sensitive than NAATs
  • Subsequent confirmatory NAAT within 48 hours may be recommended in the following cases:
    • Negative results in symptomatic patients with a high likelihood of COVID-19
    • Positive results in asymptomatic individuals in whom concern for infection is low
  • Potential false-positive results due to past or present infection with other coronavirus strains
  • Not necessarily helpful for evaluating the likelihood of future infection
  • A high number of false-positive results can occur in a population with a low prevalence of COVID-19 cases.

NAAT (RT-PCR) is the gold standard for detecting active SARS-CoV-2 infection. [4]

SARS-CoV-2 PCR testing can be negative early in the disease or may produce a false-negative test result due to technical errors (e.g., inaccurate specimen collection). [42]


The differential diagnoses listed here are not exhaustive.

Approach [43]

Severity assessment [37][38]

COVID-19 disease spectrum [38]
Clinical presentation
Asymptomatic COVID-19
  • Positive virologic test
  • No symptoms
Mild COVID-19
Moderate COVID-19
Severe COVID-19
Critical COVID-19

Risk factors for severe COVID-19 [44]

General principles [45]

Patients with mild or asymptomatic disease who do not have risk factors for progression to severe COVID-19 can usually be managed in an outpatient setting.

  • Advise patients on methods to minimize the spread of infection, e.g.:
    • Staying home and isolating in a separate well-ventilated room when possible
    • Wearing a mask when it is necessary to be around other people
    • Hand hygiene
    • For more details, see https://www.cdc.gov/coronavirus/2019-ncov/if-you-are-sick/steps-when-sick.html
  • Discuss symptom monitoring and advise patients to seek medical attention if they experience any of the following:

Medical management [46]

Supportive care

Pharmacotherapy [46]

Pharmacotherapy for nonhospitalized high-risk adults with COVID-19 [46]
Medication Timing of administration after symptom onset Clinical considerations
Ritonavir-boosted nirmatrelvir
  • Within 5 days
Remdesivir
  • Within 7 days
Molnupiravir
  • Within 5 days
  • Consider only if other treatment options are unavailable or contraindicated.
  • Possible teratogen
Bebtelovimab
  • Within 7 days

Systemic corticosteroids are not indicated for management of patients with mild to moderate COVID-19. Patients receiving corticosteroids for other indications should continue use as prescribed. [4]

Do not start antithrombotic therapy in nonhospitalized patients with COVID-19. Chronic antithrombotic therapy for preexisting medical conditions should be continued. [4][47]

Monitoring and follow-up [4]

General principles

Patients with moderate to severe COVID-19 often require hospitalization.

Laboratory studies [35]

Laboratory parameters in COVID-19 are nonspecific but are useful in evaluating for organ dysfunction

Chest imaging in COVID-19 [52][53][54]

Imaging alone cannot confirm a diagnosis of COVID-19. Imaging findings suggestive of COVID-19 should be verified via COVID-19 virus testing. [53][54]

Chest CT can detect parenchymal changes early in the course of COVID-19 and, compared to a chest x-ray, has higher sensitivity in detecting disease progression and alternative diagnoses. [54]

Chest x-ray [54]

  • Indications: : often the initial test to asses disease severity and rule out differential diagnoses (e.g., pneumothorax, pleural effusion)
  • Supportive findings

Chest ultrasound [55]

POCUS may also be used to assess hemodynamic status in critically ill patients (IVC POCUS) and those with deep vein thrombosis. [55]

Chest CT (noncontrast) [53][56]

  • Indications: : hospitalized symptomatic patients with other specific clinical indications for a chest CT [53]
  • Findings

Imaging studies can not be used to diagnose COVID-19.

Screening for VTE [47]

There is insufficient evidence to recommend routine screening for VTE in patients with COVID-19, even in those with elevated coagulation markers. [47]

Supportive care [57][58]

Oxygen therapy [57][58]

A trial of awake prone positioning can be considered in individuals with hypoxemia that persists despite HNFC, but the procedure is not routinely recommended in patients who require supplemental oxygen without mechanical ventilation. [58][59]

Awake prone positioning should not prevent or delay intubation in patients with indications for invasive mechanical ventilation. [58]

Pharmacotherapy [57]

  • Pharmacotherapy for hospitalized patients with COVID-19 varies according to disease severity.
  • Pharmacologic options include remdesivir, dexamethasone, and other immunomodulators.
  • For the latest guideline recommendations, see https://www.covid19treatmentguidelines.nih.gov/therapeutic-management.
  • For possible drug interaction, see “https://www.covid19-druginteractions.org/checker.”
Pharmacotherapy regimens of hospitalized patients with COVID-19 [57]
Disease severity

Recommended treatment

(See table below for dosage information)

Not requiring O2 therapy
  • Consider remdesivir for patients at high risk of disease progression.
Requiring O2 therapy
Requiring high-flow O2 therapy or noninvasive ventilation
Requiring mechanical ventilation or ECMO

Pharmacotherapy is indicated for all hospitalized patients who require supplemental oxygen. [57]

Overview of medications for COVID-19 in hospitalized patients [57]
Medication class Specific agents Mechanism of action Clinical considerations
Antivirals
  • Remdesivir
  • May cause liver injury; check LFTs before starting.
  • May be used in pregnant patients
Corticosteroids
  • Reduces the inflammatory response caused by COVID-19
IL-6 pathway inhibitors
JAK inhibitors [61]
  • Baricitinib
  • Tofacitinib

Patients started on remdesivir should complete the full treatment course, even if they experience disease progression. [57]

JAK inhibitors should not be combined with IL-6 pathway inhibitors (except in a clinical trial). [57]

Antithrombotic therapy in COVID-19 [47]

Antithrombotic therapy is recommended in all hospitalized patients with COVID-19 unless there are contraindications for anticoagulation. [4]

Discontinue VTE prophylaxis at discharge. The decision to continue VTE prophylaxis at discharge in pregnant or postpartum patients should be individualized. [47]

Postdischarge management [57]

CDC recommendations; for discontinuation of isolation vary based on symptoms and disease severity; for the latest guidelines, see: https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html [62]

  • All individuals with COVID-19 should isolate for at least 5 days (day 0: day of symptom onset or positive COVID-19 test).
  • Mildly symptomatic or asymptomatic individuals may consider an antigen test around day 5 to determine need for further isolation. [63]
    • Positive antigen test: Isolation is required for a total of 10 days.
    • Negative antigen test: Isolation may be discontinued if other parameters are fulfilled.

Typically, patients with asymptomatic, mild, or moderate COVID-19 are no longer infectious 10 days after symptom onset. [62]

Discontinuing isolation in patients with COVID-19 [62]
Patient group When isolation can stop
Asymptomatic COVID-19
  • 5 full days have passed without symptoms since the date of the positive COVID-19 test AND
  • The individual can wear a well-fitting mask for 5 more days after the 5-day isolation period.
  • Asymptomatic individuals living in congregate settings should isolate for a full 10 days.
Mild COVID-19
  • 5 full days have passed since symptoms developed AND
  • No fever for ≥ 24 hours without antipyretics AND
  • Symptoms are improving AND
  • The individual can wear a well-fitting mask for 5 more days after the 5-day isolation period.
Moderate COVID-19
  • 10 days have passed since symptom onset.
Severe COVID-19
Critical COVID-19
  • 10–20 days have passed since symptoms developed AND
  • No fever for at least 24 hours without antipyretics AND
  • Symptoms are improving.
  • Consider a test-based strategy before discontinuing isolation.
Moderately to severely immunocompromised patients
  • ≥ 20 days have passed since symptom onset or a positive test for COVID-19 AND
  • Negative COVID-19 tests on ≥ 2 respiratory samples collected ≥ 24 hours apart AND
  • In symptomatic patients, an improvement of symptoms and no fever for ≥ 24 hours without antipyretics
  • Consult infectious disease specialists before discontinuing isolation.

Loss of smell and taste may persist for several weeks after recovery and should not delay the end of isolation. [64]

We list the most important complications. The selection is not exhaustive.

This section provides recommendations for specific patient groups during the COVID-19 pandemic.

Overview [67]

  • Pregnant and recently pregnant individuals are at higher risk of severe COVID-19.
  • Counsel pregnant individuals on ways to minimize the risk of infection (see “Protective measures for the general public” in the section “Prevention”).
  • Vaccination against COVID-19 is recommended for pregnant and breastfeeding individuals. [68]
  • Treatment options for pregnant patients with COVID-19 are generally the same as those for nonpregnant patients.

Management of COVID-19 during pregnancy [67][69]

Patients with symptoms suggestive of moderate to severe disease, or those with risk factors for severe COVID-19 require in-person evaluation.

Molnupiravir is potentially teratogenic and should be avoided, if feasible, in pregnant individuals. [46]

In pregnant patients with COVID-19, maintain oxygen saturation ≥ 95% on room air. [66]

Management of COVID-19 in the peripartum period [69]

  • Infection with COVID-19 is not a contraindication for vaginal delivery.
  • Mothers with COVID-19 do not need to isolate from their babies after birth.
  • Breastfeeding
    • Individuals not receiving pharmacotherapy for COVID-19 can safely breastfeed infants.
    • The decision to continue breastfeeding while on pharmacotherapy for COVID-19 should be individualized.

Vertical transmission of SARS-CoV-2 is uncommon.

Complications [71]

Symptomatic COVID-19 during pregnancy is associated with an increased risk of:

Overview [36][73][74]

The Moderna and Janssen vaccines are not currently recommended for use in individuals < 18 years of age. [75]

Management [73][76]

Given limited data in children, the decision to use pharmacological treatments should be made after weighing the risks and benefits for each patient.

Multisystem inflammatory syndrome in children (MIS-C) [73][74]

MISC-C is a complication of COVID-19 in children that manifests with hyperinflammation, severe illness, and involvement of multiple organ systems.

Remdesivir is not recommended for patients with MIS-C. [73]

Overview [79]

  • Factors that may increase the risk of infection in patients with physical or intellectual disabilities include:
    • Need for a support person to assist with mobility
    • Difficulty implementing personal protective measures, e.g., due to cognitive impairment
    • Living in a congregate setting, e.g., a nursing home
    • Delayed diagnosis, e.g., individuals with impaired speech or cognition may have difficulty communicating symptoms
  • Some comorbidities that are risk factors for severe COVID-19 are more common in individuals with disabilities.

Patient considerations [79]

  • Vaccinate eligible individuals.
  • Work with the patient to develop an individualized plan for reducing infection risk.
  • Organize backup support in case the current support person becomes sick or is quarantined.
  • Establish reliable methods for seeking immediate assistance (e.g., preprogrammed phone numbers)
  • Ensure that the patient has sufficient supplies of household items, medication, and medical equipment.
  • See also “Protective measures for the general public” in the section “Prevention.”
  • The risk of death from COVID-19 increases with age. [80][81]
  • Death rates are higher among unvaccinated individuals compared to vaccinated individuals. [2]
  • Death rates are higher among vaccinated individuals who have not received a booster compared to those who have received a booster. [2]

Prior infection with SARS-CoV-2 provides immunity against reinfection, but it is not yet known how long that protection lasts. [82]

Protective measures for the general public [83]

  • Practice hand hygiene, cough etiquette, and avoid touching the face (see “Hand hygiene” for details).
  • Masks can provide additional protection for individuals ≥ 2 years old.
    • Masks should have a close fit over the nose and mouth.
    • N95 and K95 masks offer greater protection than surgical masks.
    • Cloth masks provide the least protection.
  • Follow public health guidance to reduce spread of COVID-19
  • COVID-19 testing is recommended:
    • After close contact with infected individuals
    • Individuals with symptoms suggestive of COVID-19
  • All eligible individuals should be vaccinated.
  • See the CDC website for additional guidance: https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/prevention.html

COVID-19 vaccines [75]

See https://www.cdc.gov/vaccines/covid-19/clinical-considerations/interim-considerations-us.html#recommendations for the most recent guidelines.

COVID-19 vaccines [75]
Name Type Age group (United States) Immunization schedule
(All COVID-19 vaccines are administered intramuscularly )
Pfizer-BioNTech COVID-19 vaccine [84]
  • ≥ 5 years
  • Primary series: 2 doses administered 3 weeks apart
  • Booster
    • ≥ 5 months after the second dose of the primary series
    • Individuals ≥ 50 years of age can receive a second booster ≥ 4 months after the first booster.
Moderna COVID-19 vaccine [85]
  • ≥ 18 years
  • Primary series: 2 doses administered 4 weeks apart
  • Booster
    • ≥ 5 months after the second dose of the primary series
    • Individuals ≥ 50 years of age can receive a second booster ≥ 4 months after the first booster.

Janssen COVID-19 vaccine (Johnson & Johnson vaccine) [86]

  • ≥ 18 years
  • Primary series: single dose
  • Booster
    • ≥ 2 months after initial dose
    • Individuals ≥ 50 years of age can receive a second booster ≥ 4 months after the first booster.

Individuals ≥ 12 years of age are considered fully vaccinated after receiving their first booster; individuals 5–11 years of age are considered fully vaccinated two weeks after receiving the second dose of the PfizerBioNTech COVID-19 vaccine.

While vaccinated individuals can still contract COVID-19, they have a significantly lower risk of severe disease and death than unvaccinated individuals. [87]

Management of high-risk exposures (close contact) [88]

  • Close contact is defined as being < 6 feet from an infectious individual for ≥ 15 min.
  • Management
    • COVID-19 virological testing
      • Indicated for all vaccinated and unvaccinated individuals who have not had COVID-19 in the past 90 days
      • Testing should be performed at least five days after close contact.
    • The need for and duration of isolation varies by vaccination status: See https://www.cdc.gov/coronavirus/2019-ncov/your-health/quarantine-isolation.html for the most recent guidelines.
    • All close contacts should wear well-fitting masks around others for 10 days and avoid contact with high-risk individuals.

Preexposure prophylaxis [89]

Preventing spread of COVID-19 in healthcare settings

  • Consider telemedicine for triage and outpatient monitoring of patients with mild COVID-19 when feasible. [4]
  • Personal protective equipment (PPE) [90]
  • Strategies to reduce spread in healthcare settings include:
    • Separate locations dedicated to the evaluation of patients with known or possible COVID-19
    • Limiting the number of visitors allowed per patient
    • Screening all people entering the health care facility for symptoms of COVID-19
  • Nonurgent procedures and elective surgeries may be postponed to preserve hospital beds and resources.

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