Coronavirus Disease 2019 (COVID-19)

William M. Detmer, MD, supported by the Unbound Medicine Team

Updated: January 24, 2022

What’s New

[January 19, 2022]

Therapies for High-Risk, Nonhospitalized Patients With Mild to Moderate COVID-19

For nonhospitalized patients with mild to moderate COVID-19 who are at high risk of disease progression NIH Covid-19 Guideline Panel[1]recommends using 1 of the following therapeutics (listed in order of preference):

  • Nirmatrelvir 300 mg with ritonavir 100 mg (Paxlovid) orally twice daily for 5 days, initiated as soon as possible and within 5 days of symptom onset in those aged ≥12 years and weighing ≥40 kg (AIIa).
    • Ritonavir-boosted nirmatrelvir (Paxlovid) has significant and complex drug-drug interactions, primarily due to the ritonavir component of the combination.
    • Before prescribing ritonavir-boosted nirmatrelvir (Paxlovid), clinicians should carefully review the patient’s concomitant medications, including over-the-counter medications and herbal supplements, to evaluate potential drug-drug interactions. See the Panel’s statement on the drug-drug interactions for ritonavir-boosted nirmatrelvir (Paxlovid) for details.
  • Sotrovimab 500 mg as a single IV infusion, administered as soon as possible and within 10 days of symptom onset in those aged ≥12 years and weighing ≥40 kg (AIIa).
    • Because Omicron has become the dominant VOC in the United States and real-time testing to identify rare, non-Omicron variants is not routinely available, the Panel recommends against using bamlanivimab plus etesevimab or casirivimab plus imdevimab (AIIa).
    • Sotrovimab should be administered in a setting where severe hypersensitivity reactions, such as anaphylaxis, can be managed. Patients should be monitored during the infusion and observed for at least 1 hour after infusion.
  • Remdesivir 200 mg IV on Day 1, followed by remdesivir 100 mg IV daily on Days 2 and 3, initiated as soon as possible and within 7 days of symptom onset in those aged ≥12 years and weighing ≥40 kg (BIIa).
    • Because remdesivir requires IV infusion for 3 consecutive days, there may be logistical constraints to administering remdesivir in many settings.
    • Remdesivir is currently approved by the FDA for use in hospitalized individuals; therefore, outpatient treatment would be an off-label indication.
    • Remdesivir should be administered in a setting where severe hypersensitivity reactions, such as anaphylaxis, can be managed. Patients should be monitored during the infusion and observed for at least 1 hour after infusion.
  • Molnupiravir 800 mg orally twice daily for 5 days, initiated as soon as possible and within 5 days of symptom onset in those aged ≥18 years ONLY when none of the above options can be used (CIIa).
    • The FDA EUA states that molnupiravir is not recommended for use in pregnant patients due to concerns about the instances of fetal toxicity observed during animal studies. However, when other therapies are not available, pregnant people with COVID-19 who are at high risk of progressing to severe disease may reasonably choose molnupiravir therapy after being fully informed of the risks, particularly those who are beyond the time of embryogenesis (i.e., >10 weeks’ gestation). The prescribing clinician should document that a discussion of the risks and benefits occurred and that the patient chose this therapy.
    • There are no data on the use of molnupiravir in patients who have received COVID-19 vaccines, and the risk-to-benefit ratio is likely to be less favorable because of the lower efficacy of this drug.
  • Detailed statement

[January 5, 2022]

Tixagevimab Plus Cilgavimab (Evusheld) for Pre-Exposure Prophylaxis in Specific Groups

The NIH Covid-19 Guideline Panel[1] recommends using tixagevimab plus cilgavimab as SARS-CoV-2 PrEP for adults and adolescents (aged ≥12 years and weighing ≥40 kg) who do not have SARS-CoV-2 infection, who have not been recently exposed to an individual with SARS-CoV-2 infection, AND who:

  • Are moderately to severely immunocompromised and may have an inadequate immune response to COVID-19 vaccination (BIIa); or
  • Are not able to be fully vaccinated with any available COVID-19 vaccines due to a documented history of severe reactions to a COVID-19 vaccine or any of its components (AIIa).
  • Detailed statement

Anticoagulation in Hospitalized Patients With COVID-19

  • Several randomized controlled trials have evaluated the role of therapeutic doses of heparin in reducing venous thromboembolism or mortality in patients hospitalized for COVID-19.
  • The NIH Panel recommendations recommendations on the use of anticoagulation therapy in hospitalized, nonpregnant adults with COVID-19 who are receiving supplemental oxygen, presented according to whether the patient is receiving intensive care unit level of care.

Patient Prioritization for Treatment

Priorities for anti-SARS-CoV-2 mAb therapy based on 4 key elements: age, vaccination status, immune status, and clinical risk factors. The groups are listed by tier in descending order of priority.[1]

1

  • Immunocompromised individuals not expected to mount an adequate immune response to COVID-19 vaccination or SARS-CoV-2 infection due to their underlying conditions, regardless of vaccine status (see Immunocompromising Conditions); or
  • Unvaccinated individuals at the highest risk of severe disease (anyone aged ≥75 years or anyone aged ≥65 years with additional risk factors).

2

  • Unvaccinated individuals at risk of severe disease not included in Tier 1 (anyone aged ≥65 years or anyone aged < 65 years with clinical risk factors)

3

  • Vaccinated individuals at high risk of severe disease (anyone aged ≥75 years or anyone aged ≥65 years with clinical risk factors)
Note: Vaccinated individuals who have not received a COVID-19 vaccine booster dose are likely at higher risk for severe disease; patients in this situation within this tier should be prioritized for treatment.

4

  • Vaccinated individuals at risk of severe disease (anyone aged ≥65 years or anyone aged < 65 with clinical risk factors)
Note: Vaccinated individuals who have not received a COVID-19 vaccine booster dose are likely at higher risk for severe disease; patients in this situation within this tier should be prioritized for treatment.

COVID-19 History

  • In late 2019, a new coronavirus – not seen previously in humans – was identified as the cause of human illness in Wuhan, China and given the name "novel coronavirus" (2019-nCoV).
  • By late January 2020, the outbreak was declared a public health emergency of international concern by WHO and US Centers for Disease Control and Prevention (CDC).[2],[3]
  • By mid February 2020, the virus was renamed Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and the disease it causes was named COVID-19.[4]
  • in March 2020, the outbreak was categorized as a pandemic by WHO.[5]

Epidemiology

  • Spread by human-to-human transmission via respiratory droplets or fomites.
  • Median incubation period from exposure to symptoms onset is 4–5 days; ~97% develop symptoms within 12 days from SARS-CoV-2 infection.[6]
  • Individuals of all ages are at risk for SARS-CoV-2 infection and severe disease. However, the probability of serious COVID-19 disease is higher in people aged ≥60 years, those living in a nursing home or long-term care facility, and those with chronic medical conditions.
  • Spectrum of illness can range from asymptomatic infection to severe pneumonia with acute respiratory distress syndrome and death.

Drug Treatment

General recommendations

  • The NIH COVID-19 Treatment Guidelines Panel recommends the following strategies for managing patients with different severities of disease.[1]
  • Details on each therapeutic agent can be found below this section.
Therapeutic Management of Hospitalized Patients with COVID-19
Drug Treatment of Patient with COVID-19
  • Clarification that the recommendation for using remdesivir without dexamethasone applies to patients who are early in their disease course and who require minimal supplemental oxygen.
  • Rating for the recommendation on using dexamethasone plus remdesivir has been changed from BIII to BIIb based on data from observational studies.
  • A new recommendation has been added: For patients on dexamethasone who have rapidly increasing oxygen needs and systemic inflammation, add a second immunomodulatory drug (e.g., baricitinib, tocilizumab) (CIIa).
NIH COVID-19 Treatment Guidelines Panel’s Recommendations for hospitalized patients with COVID-19.
New as of December 16, 2021
Source: US National Institutes of Health COVID-19 Treatment Guidelines.[1]
Dosing Regimens for the Drugs Recommended

Remdesivir

RDV 200 mg IV once, then RDV 100 mg IV once daily for 4 days or until hospital discharge.

  • If the patient progresses to more severe illness, complete the course of RDV.
  • For a discussion on using RDV in patients with renal insufficiency, see Remdesivir.

Dexamethasone

DEX 6 mg IV or PO once daily for up to 10 days or until hospital discharge.

  • If DEX is not available, an equivalent dose of another corticosteroid may be used.
  • For more information, see Corticosteroids.

Baricitinib

Baricitinib dose is dependent on eGFR; duration of therapy is up to 14 days or until hospital discharge.

  • eGFR ≥60 mL/min/1.73 m2: Baricitinib 4 mg PO once daily
  • eGFR 30 to < 60 mL/min/1.73 m2: Baricitinib 2 mg PO once daily
  • eGFR 15 to < 30 mL/min/1.73 m2: Baricitinib 1 mg PO once daily
  • eGFR < 15 mL/min/1.73 m2: Baricitinib is not recommended.

Tofacitinib

Tofacitinib 10 mg PO twice daily for up to 14 days or until hospital discharge.

  • Use as an alternative immunomodulatory drug if baricitinib is not available or not feasible to use (BIIa).
  • eGFR < 60 mL/min/1.73 m2: Tofacitinib 5 mg PO twice daily

Tocilizumab

Tocilizumab 8 mg/kg actual body weight (up to 800 mg) administered as a single IV dose.

  • In clinical trials, a third of the participants received a second dose of tocilizumab 8 hours after the first dose if no clinical improvement was observed.

Sarilumab

Use the single-dose, prefilled syringe (not the prefilled pen) for SQ injection. Reconstitute sarilumab 400 mg in 100 cc 0.9% NaCl and administer as an IV infusion over 1 hour.

  • Use as an alternative immunomodulatory drug if tocilizumab is not available or not feasible to use (BIIa).
  • In the United States, the currently approved route of administration for sarilumab is SQ injection. In the REMAP-CAP trial, the SQ formulation was used to prepare the IV infusion.

Key: DEX = dexamethasone; eGFR = estimated glomerular filtration rate; IV = intravenous; PO = oral; RDV = remdesivir; SQ = subcutaneous

Recommendation Rating Scheme

Strength of Recommendation

Quality of Evidence for Recommendation

  1. Strong recommendation for the statement
  2. Moderate recommendation for the statement
  3. Optional recommendation for the statement

  1. One or more randomized trials with clinical outcomes and/or validated laboratory endpoints
  2. One or more well-designed, nonrandomized trials or observational cohort studies
    1. Other randomized trials or subgroup analyses of randomized trials
    2. Nonrandomized trials or observational cohort studies
  3. Expert opinion

Overview

  • Care is primarily supportive (see Supportive Therapy below)
  • FDA-approved therapies
    • Remdesivir [October 22, 2020] – recommended for hospitalized patients who require supplemental oxygen. See below for details.
  • Additional therapies recommended by NIH Guidelines Panel
    • Dexamethasone – for hospitalized patients only; see below for details
    • Baricitinib or tocilizumab: for certain hospitalized patients who require high-flow oxygen or non-invasive ventilation. If neither agent is available or feasible, tofacitinib can be substituted for baricitinib and sarilumab can be substituted for tocilizumab.
    • Anti-SARS-CoV-2 monoclonal antibodies: for outpatients with mild to moderate COVID-19 who are at high risk of clinical progression, as defined by the EUA criteria
      • Bamlanivimab plus etesevimab; or
      • Casirivimab plus imdevimab; or
      • Sotrovimab [preferred for regions where the Omicron variant is dominant]
  • Therapies NOT approved nor recommended except in a clinical trial
    • Hydroxychloroquine and chloroquine with or without azithromycin
    • Lopinavir/ritonavir or other HIV protease inhibitors
    • Ivermectin
    • Anti-IL-6 monoclonal antibody (siltuximab)
    • Interferons
    • Bruton’s tyrosine kinase inhibitors (e.g., acalabrutinib, ibrutinib, zanubrutinib)
    • Other Janus kinase inhibitors (e.g., ruxolitinib)
  • Many other treatments are being investigated in clinical trials

Remdesivir (Gilead)

  • On October 22, 2020 the U.S. FDA:
    • Approved remdesivir (Veklury®) for adults and pediatric patients (12 years and older and weighing at least 40 kg) for the treatment of COVID-19 requiring hospitalization. Under its approval, Veklury should only be administered in a hospital or in a healthcare setting capable of providing acute care comparable to inpatient hospital care.[7]
    • Authorized continued emergency use to treat suspected or laboratory-confirmed COVID-19 in hospitalized pediatric patients weighing 3.5 kg to less than 40 kg or hospitalized pediatric patients less than 12 years of age weighing at least 3.5 kg.

Box 1: Remdesivir (RDV) for COVID-19
NIH COVID-19 Treatment Guidelines Panel Recommendations[1]

For Hospitalized Adult and Pediatric Patients (Aged ≥12 Years and Weighing ≥40 kg)

  • For Patients Who Are Not Mechanically Ventilated and/or on ECMO:
    • Remdesivir 200 mg IV over 30–120 minutes on Day 1, followed by remdesivir 100 mg IV on Day 2 through Day 5 (AI)
    • In patients who have not shown clinical improvement after 5 days of therapy, treatment may be extended up to 10 days.
  • For Mechanically Ventilated Patients and/or Patients on ECMO:
    • Remdesivir 200 mg IV over 30–120 minutes on Day 1, followed by remdesivir 100 mg IV on Day 2 through Day 10 (AIII)

Suggested Dose in EUAa for Hospitalized Pediatric Patients Weighing 3.5 kg to < 40 kg or Aged < 12 Years and Weighing ≥3.5 kg

  • For Patients Weighing 3.5 kg to < 40 kg:
    • Remdesivir 5 mg/kg IV over 30–120 minutes on Day 1, followed by remdesivir 2.5 mg/kg once daily starting on Day 2
    • For patients who are not mechanically ventilated and/or on ECMO, the recommended treatment duration is 5 days. If patients have not shown clinical improvement after 5 days of therapy, treatment may be extended up to 10 days.
    • For mechanically ventilated patients and/or patients on ECMO, the recommended treatment duration is 10 days.
  • For Patients Aged < 12 Years and Weighing ≥40 kg:
    • Same dose as for adults and children aged >12 years and weighing >40 kg

Not Recommended

  • If eGFR is < 30 mL/min
  • May need to be discontinued if ALT levels increase to >10 times the upper limit of normal and should be discontinued if there is an increase in ALT level and signs or symptoms of liver inflammation are observed.

aThe FDA EUA permits the emergency use of RDV for the treatment of suspected COVID-19 or laboratory-confirmed SARS-CoV-2 infection in hospitalized pediatric patients weighing 3.5 kg to < 40 kg or aged < 12 years and weighing ≥3.5 kg.

ALT = alanine transaminase; ECMO = extracorporeal membrane oxygenation; eGFR = estimated glomerular filtration rate; EUA = Emergency Use Authorization; FDA = Food and Drug Administration;

Remdesivir Research Studies

  • Broad antiviral activity including against SARS-CoV-2 in vitro.[8]
  • Preliminary results of an NIH-sponsored clinical trial (ACTT; NCT04280705) published in NEJM showed remdesivir accelerated recovery from advanced COVID-19.[9]

Remdesivir

Placebo

Significance

Median Time to Recovery (Days)

11

15

p< 0.001

Mortality

8.0%

11.6%

p=0.059

Preliminary Results from Adaptive COVID-19 Treatment Trial (ACTT).[9]

  • NEJM study in patients with severe COVID-19 not requiring mechanical ventilation did not show a significant difference between a 5-day and 10-day course of remdesivir. With no placebo control, the magnitude of benefit of treatment could not be determined.[10]
  • The Lancet reported on a RCT (ClinicalTrials.gov NCT04257656) at ten hospitals in Hubei, China. Remdesivir was not associated with statistically significant clinical benefits, although some authors have concluded that the study was underpowered to detect a statistical difference.
  • NEJM study of compassionate-use remdesivir in severe COVID-19 showed clinical improvement in 36 of 53 patients (68%). However, no conclusion about true efficacy could be made from this small and non-controlled study.[11]
  • Many additional clinical trials are underway.

Dexamethasone (Corticosteroids)

Box 2: Dexamethasone for COVID-19

NIH COVID-19 Treatment Guidelines Panel[1]

  • Recommends using dexamethasone (at a dose of 6 mg per day for up to 10 days) in patients with COVID-19 who are mechanically ventilated (AI) and in patients with COVID-19 who require supplemental oxygen but who are not mechanically ventilated (BI).
  • Recommends against using dexamethasone in patients with COVID-19 who do not require supplemental oxygen (AI).
  • If dexamethasone is not available, the Panel recommends using alternative glucocorticoids such as prednisone, methylprednisolone, or hydrocortisone (AIII).

Additional Considerations

  • Whether use of other corticosteroids (e.g., prednisone, methylprednisolone, hydrocortisone) for the treatment of COVID-19 provides the same benefit as dexamethasone is unclear. The total daily dose equivalencies to dexamethasone 6 mg (oral or intravenous [IV]) for these drugs are:
    • Prednisone 40 mg
    • Methylprednisolone 32 mg
    • Hydrocortisone 160 mg
  • Half-life, duration of action, and frequency of administration vary among corticosteroids.
    • Long-Acting Corticosteroid: Dexamethasone; half-life: 36 to 72 hours, administer once daily.
    • Intermediate-Acting Corticosteroids: Prednisone and methylprednisolone; half-life: 12 to 36 hours, administer once daily or in two divided doses daily.
    • Short-Acting Corticosteroid: Hydrocortisone; half-life: 8 to 12 hours, administer in two to four divided doses daily.
  • Hydrocortisone is commonly used to manage septic shock in patients with COVID-19; please refer to the Critical Care section for more information. Unlike other corticosteroids previously studied in ARDS, dexamethasone lacks mineralocorticoid activity and thus has minimal effect on sodium balance and fluid volume.

Dexamethasone Research Studies

  • Preliminary results from the UK RECOVERY trial published in NEJM showed Dexamethasone 6 mg once daily, taken orally or by injection for 10 days reduced the 28 day mortality rate by 17% (0.83 (0.74 to 0.92); P=0.0007) with the greatest benefit among patients needing ventilation (see table below).
Table 3: Dexamethasone Effect on 28-Day Mortality

Respiratory Support
at Randomization

Dexamethasone

% mortality

Usual Care

% mortality

Rate Ratio
(95% CI)

Invasive mechanical ventilation

29.3

41.4

0.64 (0.51 to 0.81)

Oxygen only

23.3

26.2

0.82 (0.72 to 0.94)

No oxygen received

17.8

14.0

1.19 (0.91 to 1.55)

Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report.[12]

CI = Confidence Interval

Anti-SARS-CoV-2 Monoclonal Antibodies

Box 3: Anti-SARS-CoV-2 Monoclonal Antibodies

NIH COVID-19 Treatment Guidelines Panel[1]

  • Recommends the using one of the following anti-SARS-CoV-2 monoclonal antibody (mAb) products (listed alphabetically and not in order of preference) to treat nonhospitalized patients with mild to moderate COVID-19 who are at high risk of clinical progression, as defined by criteria in the Food and Drug Administration (FDA) Emergency Use Authorizations (EUAs) for the products:
    • Bamlanivimab 700 mg plus etesevimab 1,400 mg (or weight-based dosing for pediatric patients weighing < 40 kg) administered as an intravenous (IV) infusion in regions where the combined frequency of potentially resistant SARS-CoV-2 variants is low (see the FDA webpage Bamlanivimab and Etesevimab Authorized States, Territories, and U.S. Jurisdictions); or
    • Casirivimab 600 mg plus imdevimab 600 mg administered as an IV infusion (AIIa) or as subcutaneous (SQ) injections (BIII); or
    • Sotrovimab 500 mg administered as an IV infusion
  • Recommends using one of the following anti-SARS-CoV-2 monoclonal antibodies (listed alphabetically) as post-exposure prophylaxis (PEP) for people who are at high risk of progressing to severe COVID-19 if infected with SARS-CoV-2 AND who have the vaccination status AND exposure history outlined in the text below:
    • Bamlanivimab 700 mg plus etesevimab 1,400 mg administered as an intravenous (IV) infusion (BIII); or
    • Casirivimab 600 mg plus imdevimab 600 mg administered as subcutaneous injections (AI) or an IV infusion (BIII).

Blood-Derived Products

Box 5: Blood-Derived Products in COVID-19

NIH COVID-19 Treatment Guidelines Panel[1]

  • Recommends against the use of COVID-19 convalescent plasma for the treatment of COVID-19 in hospitalized patients without impaired humoral immunity (AI).
  • Insufficient evidence to recommend either for or against the use of COVID-19 convalescent plasma for the treatment of COVID-19 in:
    • Nonhospitalized patients without impaired humoral immunity; and
    • Nonhospitalized or hospitalized patients with impaired humoral immunity.
  • Recommends against the use of the following blood-derived products for the treatment of COVID-19, except in a clinical trial:
    • Mesenchymal stem cells (AIIb)
    • Non-SARS-CoV-2-specific intravenous immunoglobulin (IVIG) (AIII). This recommendation should not preclude the use of IVIG when it is otherwise indicated for the treatment of complications that arise during the course of COVID-19.

Convalescent Plasma Research Studies

  • PNAS: In an uncontrolled case series of 10 adult patients with severe COVID-19 who were given one dose of convalescent plasma with the neutralizing antibody titers above 1:640, clinical symptoms significantly improved with an increase of oxyhemoglobin saturation within 3 d, accompanied by rapid neutralization of viremia.[13]
  • JAMA: In an uncontrolled case series of 5 critically ill patients with COVID-19 and ARDS, administration of convalescent plasma containing neutralizing antibody was followed by improvement in clinical status.[14]
  • U.S. FDA has provided guidance for the use of COVID-19 convalescent plasma under an Emergency Investigational New Drug Application
  • Other Convalescent Plasma Clinical Trials are underway.

Hydroxychloroquine (HCQ) and Chloroquine (CQ)

Box 6: Hydroxychloroquine / Chloroquine in COVID-19

NIH COVID-19 Treatment Guidelines Panel[1]

  • Recommends against the use of chloroquine or hydroxychloroquine with or without azithromycin in hospitalized or nonhospitalized patients (AI).
  • Recommends against the use of high-dose chloroquine (600 mg twice daily for 10 days) for the treatment of COVID-19 (AI).

Hydroxychloroquine Research Studies

  • Inhibits growth of SARS-CoV-2 in vitro,[15] but no clinical trials have demonstrated conclusively their effectiveness in humans.
  • NEJM article reported that HCQ, alone or with azithromycin, did not improve clinical status in patients hospitalized with mild-moderate COVID-19 at 15 days as compared with standard care.[16]
  • Annals of Internal Medicine reported on randomized trial of of 491 patients where HCQ given to nonhosptialized adults with early COVID-19 did not substantially reduce symptom severity or improve outcomes
  • UK RECOVERY trial: HCQ treatment arm stopped after preliminary analysis showed HCQ did not reduce mortality or improve other outcomes in hospitalized COVID-19 patients.[17]
  • NEJM reported a randomized trial showing HCQ did not prevent COVID-19 infection when used as postexposure prophylaxis within 4 days after exposure.[18]
  • Observational study published in JAMA showed amongst 1,438 hospitalized COVID-19 patients those receiving hydroxychloroquine, azithromycin, or both had no significant differences in mortality.[19]
  • Observational study published in NEJM showed HCQ not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death.[20]
  • An increasing number of studies have reported clinically significant QT Interval prolongation from CQ/HCQ +/- azithromycin[19], with some authors cautioning "first, do no harm."[21]

Other Antiviral Drugs

Box 7: Other Antiviral Drugs in COVID-19

NIH COVID-19 Treatment Guidelines Panel[1]

  • Insufficient data to recommend either for or against the following drugs except in a clinical trial:
    • Ivermectin for the treatment of COVID-19
  • Recommends against using the following drugs to treat COVID-19 except in a clinical trial:
    • Lopinavir/ritonavir (AI) or other HIV protease inhibitors (AIII) to treat COVID-19.
    • Nitazoxanide for the treatment of COVID-19, except in a clinical trial (BIIa).

Lopinavir-ritonavir (AbbVie; Kaletra, Aluvia)

  • Showed "no benefit" in hospitalized adult patients with severe COVID-19 according to a study published in the New England of Journal of Medicine.[22]
  • Many other trials are underway, see Lopinavir-Ritonavir Clinical Trials.

Other Immunomodulators

Box 8: Other Immunomodulators in COVID-19

NIH COVID-19 Treatment Guidelines Panel[1]

  • There are insufficient data for the Panel to recommend either for or against the use of the following immunomodulators for the treatment of COVID-19:
    • Anakinra
    • Colchicine for nonhospitalized patients
    • Fluvoxamine
    • Granulocyte-macrophage colony-stimulating factor inhibitors for hospitalized patients
    • Inhaled budesonide
    • Interferon beta for the treatment of early (i.e., < 7 days from symptom onset) mild to moderate COVID-19
  • Recommends against the use of the following immunomodulators for the treatment of COVID-19, except in a clinical trial:
    • Baricitinib plus tocilizumab (AIII)
    • Canakinumab (BIIa)
    • Colchicine for hospitalized patients (AI) or nonhospitalized patients with COVID-19, except in a clinical trial (BIIa).
    • Systemic interferon beta for the treatment of hospitalized patients with COVID-19 (AI).
    • Interferon alfa or lambda for the treatment of hospitalized patients with COVID-19, except in a clinical trial (AIIa).
    • Interferons for the treatment of nonhospitalized patients with mild or moderate COVID-19, except in a clinical trial (AIIa).
    • Intravenous immunoglobulin (IVIG) (non-SARS-CoV-2-specific) for the treatment of patients with acute COVID-19 (AIII). This recommendation should not preclude the use of IVIG for multisystem inflammatory syndrome in children (MIS-C) or when it is otherwise indicated.
    • Bruton’s tyrosine kinase inhibitors (e.g., acalabrutinib, ibrutinib, zanubrutinib) (AIII)
    • JAK inhibitors other than baricitinib and tofacitinib (e.g., ruxolitinib) (AIII)
    • Siltuximab (BIII)

Supportive therapy and monitoring

Mild to Moderate Disease

  • Patients with a mild clinical presentation (absence of viral pneumonia and hypoxia) can often manage their illness at home.
  • Outpatient or inpatient monitoring may be required, depending on:
    • Clinical presentation, need for supportive care, risk factors for severe disease, and the ability to self-isolate at home.
    • Risk factors for severe illness: these patients should be monitored closely given the possible risk of progression to severe illness in the second week after symptom onset.

Severe Disease

  • Inpatient management of COVID-19 is supportive and focused on the mmanagement of complications (see below). For details see NEJM review of treatment of severe COVID-19.[23]
Complications of Severe COVID-19

  • Pneumonia
  • Acute Respiratory Distress Syndrome (ARDS)
  • Sepsis and septic shock
  • Cardiomyopathy and arrhythmia
  • Acute kidney injury
  • Complications from prolonged hospitalization
    • Nosocomial infection
    • Thromboembolism
    • Gastrointestinal bleeding
    • Critical illness polyneuropathy/myopathy

See Also

For health professionals

For the Public

References

  1. COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Available at https://www.covid19treatmentguidelines.nih.gov/. Updated: January 5, 2022.
  2. Statement on the second meeting of the International Health Regulations (2005) Emergency Committee regarding the outbreak of novel coronavirus (2019-nCoV). World Health Organization. 30 January 2020. [https://www.who.int/news-room/detail/30-01-2020-statement-on-the-second-me...]
  3. Determination that a Public Health Emergency Exists. US Department of Health and Human Services. 31 January 2020. [https://www.phe.gov/emergency/news/healthactions/phe/Pages/2019-nCoV.aspx]
  4. World Health Organization (WHO) Novel Coronavirus(2019-nCoV) Situation Report – 22. February 11, 2020. [https://www.who.int/docs/default-source/coronaviruse/situation-reports/202...]
  5. WHO Director-General’s opening remarks at the media briefing on COVID-19. World Health Organization. 11 March 2020. [https://www.who.int/dg/speeches/detail/who-director-general-s-opening-rema...]
  6. Lauer SA, Grantz KH, Bi Q, et al. The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application. Ann Intern Med. 2020.  [PMID:32150748]
  7. FDA-Approved Drugs: Remdesivir. Drugs@FDA. Accessed October 22, 2020. [https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm...]
  8. Choy KT, Yin-Lam Wong A, Kaewpreedee P, et al. Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro. Antiviral Res. 2020.  [PMID:32251767]
  9. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the Treatment of Covid-19 - Preliminary Report. N Engl J Med. 2020.  [PMID:32445440]
  10. Goldman JD, Lye DCB, Hui DS, et al. Remdesivir for 5 or 10 Days in Patients with Severe Covid-19. N Engl J Med. 2020.  [PMID:32459919]
  11. Grein J, Ohmagari N, Shin D, et al. Compassionate Use of Remdesivir for Patients with Severe Covid-19. N Engl J Med. 2020.  [PMID:32275812]
  12. RECOVERY Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in Hospitalized Patients with Covid-19 - Preliminary Report. N Engl J Med. 2020.  [PMID:32678530]
  13. Duan K, Liu B, Li C, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci U S A. 2020;117(17):9490-9496.  [PMID:32253318]
  14. Shen C, Wang Z, Zhao F, et al. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. 2020.  [PMID:32219428]
  15. Yao X, Ye F, Zhang M, et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020.  [PMID:32150618]
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