COVID-19 (coronavirus disease 2019)

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.

We at AMBOSS are doing our best to accurately update our COVID-19 content. Considering that information about COVID-19 is changing daily, we greatly appreciate your understanding regarding any potential delays.

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• Airway management
• Acute respiratory distress syndrome (ARDS)
• Sepsis
• Pneumonia
• Nosocomial infections

• 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 is an enveloped, nonsegmented, positive-sense, ssRNA β-coronavirus. ^[6]
• The viral genome encodes:
  • Four structural proteins
    • Spike: facilitates entry by attaching to the ACE2 receptor of the host cell
    • Envelope
    • Membrane
    • Nucleocapsid: packages the viral genome into a helical ribonucleocapsid
  • 16 nonstructural proteins: form the replicase–transcriptase complex ^[7]

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

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 (droplet transmission) or aerosol particles (airborne transmission)
    • 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]

• Invasion of host cells
  1. The spike protein binds to the membrane protein angiotensin-converting enzyme 2 (ACE2). ^[28]
  2. Transmembrane protease serine 2 (TMPRSS2) activates the spike protein.
  3. Membrane fusion and uncoating of the viral RNA occur.
• Replication cycle
  • Enzymes, such as RNA polymerase or proteases, which are virally induced by endosomal viral RNA, release replicate viral components.
  • Endosomes with newly constituted viruses are released via exocytosis.

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

Effects

• Direct cytopathic effects: Particularly on the alveolar epithelium; other organs (e.g., liver, heart) can be affected as well. ^[29][30][31]
• Dysregulated immune response ; ^[32][33]
  • Activation of the immune system → release of cytokines; (e.g., tumor necrosis factor, IL-1β, IL-6) → acute inflammatory response
  • Some patients demonstrate a very large immune response resembling a “cytokine storm” that can lead to organ failure and death.

• Incubation period: 2–14 days, usually ∼ 5 days ^[4][34]
• Symptoms ^[35]
  • Often asymptomatic, especially in children ^[4][36]
  • Fever
  • Cough
  • Shortness of breath
  • Fatigue
  • Loss of smell and/or taste
  • Sore throat
  • Rhinitis
  • Headache
  • Myalgia
  • Diarrhea
  • Loss of appetite
  • Nausea and vomiting
  • Conjunctivitis (see “COVID-19 conjunctivitis”)
• Severity ^[37][38]
  • Severity ranges from asymptomatic to critical.
  • A patient's clinical presentation may change over the course of the disease.
  • See “COVID-19 disease spectrum” for details.

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.
  • Test all individuals with symptoms of and/or exposure to COVID-19 for current infection (see the latest CDC indications for testing at: https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/testing.html).
  • Collect specimens from the upper respiratory tract (e.g., nasopharyngeal, oropharyngeal).
  • Obtain a viral test (e.g., nucleic acid amplification test) or antigen test to diagnose current infection.
• 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]

• For all individuals: Obtain an upper respiratory tract specimen.
  • Preferred method: nasopharyngeal specimen (NP specimen)
  • Alternative methods
    • Oropharyngeal (OP) swab (i.e., throat swab)
    • Nasal midturbinate (NMT) swab
    • Anterior nares specimen
    • Saliva specimen
    • Nasopharyngeal wash/aspirate or nasal aspirate
  • If using both NP and OP swabs: Combine in a single tube.
• For mechanically ventilated individuals with a negative upper respiratory tract specimen: Obtain a lower respiratory tract aspirate or bronchoalveolar lavage.

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

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]

• Common cold
• Influenza
• Allergic rhinitis
• See also “Differential diagnosis of dyspnea” and “Differential diagnosis of cough.”

The differential diagnoses listed here are not exhaustive.

Approach ^[43]

• Triage patients via telemedicine when possible.
• Determine site of care based on disease severity and the presence of risk factors for severe COVID-19.
  • Asymptomatic or mild disease in low-risk patients: outpatient management
  • Moderate to severe disease, or risk factors for severe COVID-19: in-person evaluation; hospitalization if needed
• Patients requiring in-person evaluation: Consult institutional guidelines regarding the appropriate site of care.
• See also “Preventing spread of COVID-19 in healthcare settings.”

Severity assessment ^[37][38]

Risk factors for severe COVID-19 ^[44]

• Age (strongest risk factor): older adults, especially ≥ 65 years of age
• Cancer
• Cardiovascular disease
• Cerebrovascular disease
• Chronic kidney disease
• Chronic liver disease
• Chronic lung diseases
• Diabetes mellitus type I and type II
• Mental health disorders
• Obesity (BMI ≥ 30)
• Pregnancy or recent pregnancy
• Smoking (current and/or former)
• Tuberculosis
• Immunosuppression

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:
  • Difficulty breathing
  • Persistent chest pain or pressure
  • Change in mental status (e.g., confusion)
  • Signs of hypoxia (e.g., bluish lips)

Medical management ^[46]

Supportive care

• Rest, adequate hydration, and nutrition
• Antipyretics and analgesia as needed (e.g., acetaminophen, ibuprofen)
• Antitussives as needed (e.g., dextromethorphan, benzonatate)
• Prone positioning may relieve dyspnea.

Pharmacotherapy ^[46]

• Indications: patients with risk factors for progression to severe COVID-19
• Preferred agents: ritonavir-boosted nirmatrelvir, remdesivir
• Alternatives (only if preferred agents are not available): molnupiravir
• Not currently recommended: systemic glucocorticoids, chloroquine, hydroxychloroquine, azithromycin, ivermectin, bebtelovimab
• For possible drug interaction, see “https://www.covid19-druginteractions.org/checker.”

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]

• Monitor oximetry readings and symptom progression via telemedicine or in-person visits.
• Evaluate patients with worsening symptoms in-person.
• Advise patients that the time to recovery from COVID-19 varies.
• Encourage self-isolation until criteria for discontinuation of isolation in patients with COVID-19 are met.

General principles

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

• Determine patient's goals of care and obtain advance directives, if available.
• Determine severity of illness and admit patients to the appropriate level of care.
• Tailor additional diagnostics (laboratory studies, imaging) to the clinical presentation.
• For patients with complications related to COVID-19, see also the management sections in the following articles:
  • Sepsis
  • Pneumonia
  • Acute respiratory distress syndrome
  • Airway management
  • Mechanical ventilation
  • Venous thromboembolism (VTE)

Laboratory studies ^[35]

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

• Routine studies
  • CBC: may show lymphopenia, thrombocytopenia ^[48]
  • Basic metabolic panel
    • Elevated serum creatinine in acute kidney injury ^[49]
    • Possible electrolyte abnormalities ^[50]
  • Liver chemistry: may show ↑ ALT, ↑ AST ^[51]
• Further evaluation based on clinical presentation ^[52]
  • Inflammatory markers: ↑ CRP, ↑ ferritin, ↑ lactate dehydrogenase
  • Coagulation studies: ↑ prothrombin time, ↑ D-dimer
  • Cardiac enzymes: ↑ troponin and ↑ NT-proBNP may indicate cardiac injury related to COVID-19
  • Arterial blood gas: may reveal hypoxemic respiratory failure
  • Blood cultures: Order if there is concern for bacterial coinfection.

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

• Indications
  • Features of moderate COVID-19 or severe COVID-19
  • Worsening respiratory status
  • Patients with mild COVID-19 with risk factors for progression to severe COVID-19
• Modalities: Initial imaging studies may include chest x-ray, chest ultrasound, and chest CT.
• Important consideration: Imaging findings in COVID-19 are generally nonspecific and resemble findings in other viral respiratory infections.

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 assess disease severity and rule out differential diagnoses (e.g., pneumothorax, pleural effusion)
• Supportive findings
  • Pulmonary consolidations
  • Unilateral or bilateral opacities
  • Progression to diffuse opacities suggests development of ARDS.

Chest ultrasound ^[55]

• Indications: an alternative to chest x-ray to assess disease severity and rule out other chest pathologies (e.g., pneumothorax, pleural effusion) in critically ill patients; often performed in emergency department and ICU settings (lung POCUS)
• Supportive findings
  • Pleural thickening
  • B lines
  • Consolidations with air bronchograms

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
  • Ground glass opacities with or without consolidation (usually bilateral, peripheral, and posterior)
  • Interlobular septal thickening
  • The combination of the above findings is often referred to as a “crazy-paving pattern.”

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

Screening for VTE ^[47]

• Indications
  • Patients with features of DVT and/or features of pulmonary embolism (PE)
  • Patients with sudden or rapid clinical deterioration
• Modalities
  • Suspected PE: CT pulmonary angiography; see “Diagnostic approach to suspected PE” ^[56]
  • Suspected DVT: lower extremity venous ultrasound; see “Diagnostic approach to suspected lower-extremity DVT”

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]

• Intravenous fluid therapy as needed
• Vasopressors as needed (i.e., for shock):
  • Norepinephrine is recommended as the first-line agent.
  • See “Vasopressors and inotropes” for dosages and further details.
• Antipyretics and analgesia as needed (e.g., acetaminophen, ibuprofen)
• Antitussives as needed (e.g., benzonatate)
• If available, continuous renal replacement therapy is preferred over hemodialysis for patients with acute kidney injury and indications for dialysis.

Oxygen therapy ^[57][58]

• Goal: Maintain SpO₂ levels between 92–96% (≥ 95% in pregnant individuals).
• High flow nasal cannula (HFNC)
  • Indications: hypoxemic respiratory failure despite the use of basic oxygen delivery systems (e.g., nasal cannula, face mask)
  • HFNC unavailable: Consider noninvasive positive pressure ventilation.
  • Persistent hypoxemia despite HFNC (and no indications for invasive mechanical ventilation): Consider a trial of awake prone positioning to improve oxygenation. ^[58][59]
• Mechanical ventilation
  • Indications: See “Indications for invasive mechanical ventilation.”
  • Recommended ventilator settings for patients with COVID-19 and ARDS:
    • Tidal volume 4–8 mL/kg of predicted body weight
    • Plateau pressure < 30 cm H₂O
    • Ventilation in the prone position for 12–16 hours/day
    • High PEEP (> 10 cm H₂O)
• Extracorporeal membrane oxygenation (ECMO): There is insufficient evidence to recommend for or against the use of ECMO in patients with COVID-19 and refractory hypoxemia.
• See also “Oxygen therapy” for more information.

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

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]

• Indications: all hospitalized patients who do not have contraindications for anticoagulation
• Agents: LMWH or UFH is preferred over oral anticoagulants; LMWH is preferred over UFH.
• Dosage
  • Therapeutic dose is recommended for:
    • Venous thromboembolism (see “Management of DVT” and “Management of pulmonary embolism”)
    • Increased D-dimer and/or low-flow O₂ requirement in hospitalized nonpregnant adults
  • Prophylactic dose (pharmacological VTE prophylaxis ) is recommended for:
    • All hospitalized nonpregnant adults who do not meet indications for therapeutic anticoagulation
    • Patients requiring ICU care, including those requiring high-flow O₂
    • Hospitalized pregnant patients with COVID-19

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]

• All patients
  • Arrange for a follow-up appointment soon after discharge.
  • Stop antithrombotic therapy at the time of discharge unless the patient has a VTE.
  • Encourage self-isolation precautions until the criteria for discontinuation of isolation in patients with COVID-19 are met.
• Supplemental O₂ no longer required: Discontinue remdesivir, corticosteroids, and JAK inhibitors at the time of discharge.
• Continued requirement of supplemental O₂ at discharge: Arrange for home oxygen monitoring.

CDC recommendations for discontinuation of isolation vary based on symptoms and disease severity; see the latest CDC guidelines for details. ^[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]

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

• Thromboembolic events (e.g., ischemic stroke, pulmonary embolism)
• Hypoxemic respiratory failure
• ARDS
• Septic shock
• Cardiac disease (e.g., ischemic heart disease, heart failure) ^[65]
• Arrhythmias ^[65]
• Acute kidney injury
• Multisystem inflammatory syndrome in children (MIS-C)
• Postacute COVID-19 syndrome (“long COVID”) ^[66]
  • Refers to symptoms persisting > 4 weeks after confirmed or suspected COVID-19
  • Symptoms may include: fatigue, joint/muscle aches, chest pain, palpitations, dyspnea, cognitive impairment, mood changes, headaches, loss of smell/taste

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]

• Determine the need for in-person evaluation and hospitalization based on symptoms and comorbidities. ^[70]
• Order imaging (e.g., chest x-ray or chest CT) if clinically indicated.
• Supplemental oxygen
  • Administer supplemental oxygen if SpO₂ is < 95% on room air. ^[66]
  • Consider prone positioning or left lateral decubitus positioning in pregnant patients with persistent hypoxemia on HNFC who do not meet the criteria for invasive mechanical ventilation. ^[46]
• Consider fetal monitoring for hospitalized patients.
• Consider pharmacological treatment, if indicated.
  • Outpatients
    • Ritonavir-boosted nirmatrelvir, sotrovimab, remdesivir
    • See “Pharmacotherapy for nonhospitalized adults with COVID-19” for details.
  • Hospitalized patients
    • Remdesivir, dexamethasone
    • See “Pharmacotherapy for hospitalized patients with COVID-19” for details.
• Anticoagulation is indicated for hospitalized patients with COVID-19 (see “Antithrombotic therapy in COVID-19”). ^[47]

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:

• Hypertensive disorders of pregnancy
• Preterm birth
• Low birth weight
• Stillbirth ^[72]
• Maternal mortality

Overview ^[36][73][74]

• Children are less likely to get COVID-19.
• Clinical presentation
  • Children are often asymptomatic or develop mild COVID-19.
  • Symptoms may be similar to other viral illnesses
• Vaccination
  • The Pfizer-BioNTech COVID-19 vaccine is recommended for all children in the US ≥ 5 years of age
  • See “COVID-19 vaccines” for details.

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.

• Most children can be managed with symptomatic treatment only.
• COVID-19 pharmacotherapy for children (age ≥ 12 years; weight ≥ 40 kg)
  • Symptomatic nonhospitalized children at risk for progression to severe COVID-19
    • Ritonavir-boosted nirmatrelvir
    • OR remdesivir
  • Hospitalized children requiring supplemental oxygen: remdesivir

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.

• Clinical features may include:
  • Fever
  • Gastrointestinal symptoms
  • Mucocutaneous symptoms
  • Shock
• Diagnostic criteria: All of the following must be met. ^[77]
  • Age < 21 years
  • Fever (documented fever ≥ 38°C (100.4°F) OR report of subjective fever lasting ≥ 24 hours
  • Laboratory evidence of inflammation (e.g., ↑ CRP, ↑ ESR, ↑ neutrophils)
  • Involvement of ≥ 2 organ systems (including the hematological system)
  • Severe illness requiring hospitalization
  • Confirmed current or recent SARS-CoV-2 infection OR exposure to an individual with COVID-19 < 4 weeks prior to symptom onset
  • No other plausible diagnosis
• Treatment: combination of immunomodulatory therapy and antithrombotic therapy ^[73]
  • Immunomodulatory therapy
    • Initial treatment: intravenous immunoglobulin PLUS methylprednisolone
    • No improvement within 24 hours of initial therapy: Consider alternative immunomodulators.
  • Antithrombotic therapy (unless contraindicated)
    • All patients: low-dose aspirin
    • Patients with large coronary artery aneurysms or moderate to severe left ventricular dysfunction: therapeutic anticoagulation (with LMWH or warfarin) PLUS low-dose aspirin ^[4][78]

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
  • E.g., guidance on social distancing, quarantine, and lockdowns
  • See also “Prevention of community spread.”
• 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/coronavirus/2019-ncov/vaccines/stay-up-to-date.html for the most recent guidelines.

• Types: Three COVID-19 vaccines are available in the US.
  • Preferred: PfizerBioNTech COVID-19 vaccine or Moderna COVID-19 vaccine
  • Alternative: Johnson and Johnson's Janssen COVID-19 vaccine
• Indication
  • All individuals ≥ 5 years of age
  • Defer vaccination in patients with recent or current COVID-19 until full recovery and completion of isolation.
• Schedule: See “ACIP immunization schedule” for details.
• Contraindication: history of a severe allergic reaction to any component of the vaccine
• Adverse effects
  • Common: injection site pain and redness, headache, myalgia, fever, chills, fatigue
  • Rare
    • After Johnson and Johnson's Janssen COVID-19 vaccine
      • Thrombosis with thrombocytopenia syndrome
      • Guillain-Barré syndrome
    • After Pfizer-BioNTech COVID-19 vaccine or Moderna COVID-19 vaccine (these have been observed more frequently in young men)
      • Myocarditis
      • Pericarditis

While vaccinated individuals can still contract COVID-19, they have a significantly lower risk of severe disease and death than unvaccinated individuals. ^[89]

Management of high-risk exposures (close contact) ^[90]

• 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 for COVID-19 ^[91]

• Indications
  • Immunocompromised individuals
  • Individuals unable to be vaccinated due to severe allergic reactions
• Regimen: tixagevimab PLUS cilgavimab (long-acting anti-SARS-CoV-2 monoclonal antibodies)

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) ^[92]
  • All individuals caring for patients with confirmed or suspected COVID-19 should wear appropriate PPE.
  • See “Personal protective equipment” for instructions on safely putting on and removing PPE.
• 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.

Interested in the newest medical research, distilled down to just one minute? Sign up for the One-Minute Telegram in “Tips and links” below.

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