COVID-19 (Novel Coronavirus)

Background

• COVID-19 is an acute respiratory disease caused by SARS-CoV-2, a novel coronavirus closely related to SARS-CoV.
• The virus is transmitted person-to-person by both symptomatic and asymptomatic persons through close contact (within 6 feet) via respiratory droplets. Transmission may also occur via aerosols and possibly through contact with fomites, although this is not thought to be a primary route.
• Clinically important features of SARS-CoV-2 pathogenesis include:
  • infection of cells via binding of the viral spike protein to angiotensin-converting enzyme 2 (ACE2) receptors, with cell entry requiring type 2 transmembrane serine protease to cleave ACE2 receptor and activate viral spike protein.
  • infection of nasal and bronchial epithelial cells and pneumocytes early in infection.
  • acceleration of viral replication and compromise of epithelial-endothelial barrier integrity in later stages, resulting in a dysregulated inflammatory response and a hypercoagulable state.
  • dysregulation of renin-angiotensin-aldosterone system, which may also contribute to infection-related tissue damage.
• COVID-19 was declared a global pandemic on March 11, 2020. As of May 7, 2023, over 765 million cases including over 6.9 million deaths have been reported worldwide.
• Complications include coagulopathy, long COVID, neurologic complications, multisystem inflammatory syndrome (MIS), and others (such as post-intensive care syndrome, respiratory and cardiovascular events, renal and endocrine disorders).
• Mortality secondary to COVID-19 is highly variable and related to age, severity of disease, and comorbidities. Estimated mortality is
  • 0.3%-2.3% for all patients.
  • 10%-23% for hospitalized patients.
  • 26%-50% for patients admitted to the ICU.
  • 37%-88% for patients requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO).

Evaluation

• Mild to severe symptoms may arise 2-14 days after exposure, with mean incubation period 5 days.
• Symptoms may include:
  • fever or chills.
  • cough, shortness of breath, or difficulty breathing.
  • headache, muscle or body aches, dizziness, or fatigue.
  • sore throat, congestion, or runny nose.
  • new loss of smell or taste.
  • nausea, vomiting, diarrhea, abdominal pain, or anorexia.
  • confusion or impaired consciousness.
  • rash.
• Asymptomatic infection may occur in up to 30% of patients.
• SARS-CoV-2 nucleic acid amplification test
  • is presently the test of choice to confirm diagnosis (Strong recommendation).
  • is recommended for symptomatic individuals in the community suspected of having COVID-19 even when clinical suspicion is low (Strong recommendation).
  • may be recommended for asymptomatic individuals in certain situations such as those with immunocompromise requiring hospital admission, prior to introduction of new immunosuppressants, pre-procedure, known exposure, and hospitalization in areas with high prevalence of COVID-19.
• Various specimens may be appropriate for SARS-CoV-2 nucleic acid testing. Upper respiratory specimens including nasopharyngeal, mid-turbinate, or nasal swabs, are most commonly used.
• Serologic testing is not recommended for the diagnosis of SARS-CoV-2 infection during first 2 weeks after symptom onset (Weak recommendation).

Management

• The decision to manage a patient in an inpatient or outpatient setting should be made on a case-by-case basis.
  • Patients with mild illness (absence of viral pneumonia and hypoxia) may not require hospitalization.
  • Patients with moderate illness may require hospitalization based on comorbidities and risk for clinical progression.
  • Severe manifestations requiring hospitalization and supportive care include pneumonia, hypoxemia, acute respiratory distress syndrome (ARDS), sepsis and septic shock, cardiomyopathy, arrhythmia, and acute kidney injury.
• For nonhospitalized patients
  • Provide supportive care, consider COVID-19-specific therapy for patients at high risk for progression, take steps to reduce risk of transmission (including patient isolation), and advise patients on when to contact healthcare providers and seek in-person evaluation (Strong recommendation).
  • One of the following medications recommended for patients at high risk for disease progression; prompt treatment recommended for patients with immunocompromise (Strong recommendation).
    • Preferred therapies (listed in order of preference):
      • Nirmatrelvir/ritonavir (Paxlovid) orally twice daily for 5 days (Strong recommendation); carefully review all concomitant medications for potential drug-drug interactions.
      • Remdesivir 200 mg IV on day 1 followed by 100 mg IV on days 2 and 3 (Weak recommendation).
    • Molnupiravir may be considered if preferred therapies are unavailable, infeasible to deliver, or clinically inappropriate (Weak recommendation)
      • recommended dosing 800 mg orally twice daily for 5 days for adults aged ≥ 18 years
      • not recommended for pregnant patients due to fetal toxicity concerns, but may be chosen by patient after being fully informed of risks, especially if > 10 weeks gestation
  • no monoclonal antibodies are currently recommended in the United States due to predominant circulation of resistant Omicron variants (Strong recommendation).
• National Institutes of Health (NIH) treatment recommendations for hospitalized patients.
  • For all hospitalized patients, anticoagulant or antiplatelet therapy for underlying medical conditions should be continued unless significant bleeding develops or other contraindications present (Strong recommendation).
  • For adults who are hospitalized but do not require supplemental oxygen:
    • Dexamethasone or other systemic corticosteroids are not recommended unless patients are already receiving corticosteroids for other indications and should continue therapy as directed by their health care professional (Strong recommendation).
    • Remdesivir 200 mg IV once daily for 1 day then 100 mg IV once daily for 4 days (or until hospital discharge, whichever is first) may be considered for patients at high risk for progressing to severe COVID-19 (Weak recommendation).
    • Prophylactic antithrombotic therapy is not recommended (Strong recommendation).
    • Patients with mild-moderate COVID-19 with immunocompromise who are hospitalized for reasons other than COVID-19 should be promptly treated with antiviral agents (Strong recommendation).
  • For hospitalized adults on supplemental oxygen who do not require oxygen delivery through high-flow device, noninvasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)
    • Consider remdesivir 200 mg IV for 1 day followed by remdesivir 100 mg IV once daily for 4 days or until discharge for patients who require minimal oxygen (Weak recommendation).
    • For most other patients, consider
      • Remdesivir (at above dose and duration) plus dexamethasone 6 mg IV or orally once daily for 10 days or until discharge (Weak recommendation).
      • Dexamethasone alone if remdesivir is not available (Weak recommendation).
    • For patients on dexamethasone with rapidly increasing oxygen needs and systemic inflammation, consider addition of a second immunomodulatory therapy (baricitinib or tocilizumab preferred; alternatively tofacitinib or sarilumab if those unavailable) (Weak recommendation).
    • Anticoagulation recommendations:
      • Therapeutic dose of heparin recommended for nonpregnant patients with D-dimer levels above the upper limit of normal who are not at increased bleeding risk (Weak recommendation); continue for 14 days or until hospital discharge.
      • Prophylactic dose of heparin recommended for other patients without evidence of venous thromboembolism unless contraindicated (Strong recommendation); consider prophylactic dose for pregnant patients (Weak recommendation).
  • For hospitalized patients requiring oxygen delivery through high-flow device or noninvasive ventilation, but not invasive mechanical ventilation or ECMO:
    • Initiate dexamethasone and promptly add 1 of the following:
      • Baricitinib orally once daily for 14 days or until hospital discharge with dose dependent on estimated glomerular filtration rate (eGFR) (Strong recommendation).
      • Tocilizumab 8 mg/kg actual body weight IV (maximum 800 mg) administered as single dose (Weak recommendation).
      • If neither baricitinib or tocilizumab is available or feasible, consider either tofacitinib or sarilumab (Weak recommendation).
      • If baricitinib, tofacitinib, tocilizumab, or sarilumab are not available, dexamethasone 6 mg IV or orally once daily for 10 days or until discharge (Strong recommendation).
      • Consider addition of remdesivir to immunomodulator combination therapy in some patients, including patients with immunocompromise (Weak recommendation).
      • Anticoagulation recommendations:
        • Prophylactic dose of heparin recommended for patients without evidence of venous thromboembolism unless contraindicated (Strong recommendation); consider prophylactic dose for pregnant patients (Weak recommendation).
        • Use of intermediate dose or therapeutic dose of anticoagulation for venous thromboembolism prophylaxis recommended against except in clinical trial (Weak recommendation)
        • If patients transferred to ICU after starting on therapeutic dose of heparin, switch to prophylactic dose unless venous thromboembolism confirmed (Weak recommendation).
  • For hospitalized patients requiring invasive ventilation or ECMO
    • Initiate dexamethasone and promptly add 1 of the following:
      • Baricitinib orally once daily for 14 days or until hospital discharge with dose dependent on estimated glomerular filtration rate (eGFR) (Weak recommendation).
      • Tocilizumab 8 mg/kg actual body weight IV (maximum 800 mg) administered as single dose (Weak recommendation).
      • If neither baricitinib or tocilizumab is available or feasible, consider either tofacitinib or sarilumab (Weak recommendation).
      • If baricitinib, tofacitinib, tocilizumab, or sarilumab are not available, dexamethasone 6 mg IV or orally once daily for 10 days or until discharge (Strong recommendation).
    • In patients initially receiving remdesivir alone who progress to needing invasive mechanical ventilation or ECMO, start dexamethasone and continue remdesivir until treatment course completed.
    • Some experts may consider addition of remdesivir to dexamethasone in patients who have been recently intubated (Weak recommendation).
    • Anticoagulation recommendations:
      • Prophylactic dose of heparin recommended for patients without evidence of venous thromboembolism unless contraindicated (Strong recommendation); consider prophylactic dose for pregnant patients (Weak recommendation).
      • Use of intermediate dose or therapeutic dose of anticoagulation for venous thromboembolism prophylaxis recommended against except in clinical trial (Weak recommendation).
      • If patients transferred to ICU after starting on therapeutic dose of heparin, switch to prophylactic dose unless venous thromboembolism confirmed (Weak recommendation).
  • Considerations for patients hospitalized with COVID-19 who are immunocompromised:
    • Most patients with COVID-19 who are immunocompromised should receive therapies at the doses and durations recommended for the general population (Strong recommendation).
    • In some cases, immunomodulatory drug regimens may need to be adjusted to reduce risk of drug-drug interactions, overlapping toxicities, and secondary infections; consult with appropriate specialists about risks and benefits associated with temporary dose reduction or discontinuation (Weak recommendation).
    • Insufficient evidence for or against high-titer convalescent plasma; some clinicians would consider use in patients with severe or progressive COVID-19 and inadequate response to therapy.
  • For all hospitalized patients meeting criteria for dexamethasone, alternative corticosteroids including prednisone, methylprednisolone, or hydrocortisone may be used if dexamethasone is unavailable (Weak recommendation).
• Additional management may be needed for manifestations of severe disease, including hypoxemia and acute respiratory distress syndrome (ARDS), septic shock, and coagulopathy.

Infection Control and Prevention

• Infection control measures continue to evolve and requirements may differ regionally.
  • General community guidance includes cleaning hands often, avoiding close contact and crowded public settings, wearing a mask in indoor public places with high community transmission (N95 or equivalent preferred), testing to prevent spread, covering coughs and sneezes, cleaning and disinfecting frequently touched surfaces, and health monitoring.
  • Mask use around others is recommended for 10 days for persons with close contact.
  • Isolation is recommended for persons with confirmed or probable COVID-19 regardless of vaccination status.
• Vaccination is the most effective way to prevent COVID-19; no monoclonal antibodies are currently authorized for prophylaxis.
• Screening may be useful to identify persons who are asymptomatic and have no known or suspected exposure to SARS-CoV-2 in schools, workplace settings, for travel, or public surveillance.
• See COVID-19 Infection Control and Prevention for guidance on and efficacy of infection control, immunization, prophylaxis, and screening strategies for the prevention of COVID-19.