Potential Antiviral Drugs Under Evaluation for the Treatment of COVID-19

Last Updated: July 24, 2020

Summary Recommendations
Summary Recommendations
There are no Food and Drug Administration-approved drugs for the treatment of COVID-19. Definitive clinical trial data are needed to identify safe and effective treatments for COVID-19. In this table, the COVID-19 Treatment Guidelines Panel (the Panel) provides recommendations for using antiviral drugs to treat COVID-19 based on the available data. As in the management of any disease, treatment decisions ultimately reside with the patient and their health care provider. For more information on the antiviral agents that are currently being evaluated for the treatment of COVID-19, see Tables 2a and 2b. Remdesivir Recommendation for Prioritizing Limited Supplies of Remdesivir Because remdesivir supplies are limited, the Panel recommends that remdesivir be prioritized for use in hospitalized patients with COVID-19 who require supplemental oxygen but who are not on high-flow oxygen, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO) (BI). Recommendation for Patients with Mild or Moderate COVID-19 There are insufficient data for the Panel to recommend either for or against the use of remdesivir in patients with mild or moderate COVID-19. Recommendation for Patients with COVID-19 Who Are on Supplemental Oxygen but Who Do Not Require High-Flow Oxygen, Noninvasive or Invasive Mechanical Ventilation, or ECMO The Panel recommends using remdesivir for 5 days or until hospital discharge, whichever comes first (AI). If a patient who is on supplemental oxygen while receiving remdesivir progresses to requiring high-flow oxygen, noninvasive or invasive mechanical ventilation, or ECMO, the course of remdesivir should be completed. Recommendation for Patients with COVID-19 Who Require High-Flow Oxygen, Noninvasive Ventilation, Mechanical Ventilation, or ECMO Because there is uncertainty regarding whether starting remdesivir confers clinical benefit in these groups of patients, the Panel cannot make a recommendation either for or against starting remdesivir. Duration of Therapy for Patients Who Have Not Shown Clinical Improvement After 5 Days of Therapy There are insufficient data on the optimal duration of remdesivir therapy for patients with COVID-19 who have not shown clinical improvement after 5 days of therapy. In this group, some experts extend the total remdesivir treatment duration to up to 10 days (CIII). Chloroquine or Hydroxychloroquine The Panel recommends against the use of chloroquine or hydroxychloroquine for the treatment of COVID-19, except in a clinical trial (AII). The Panel recommends against the use of high-dose chloroquine (600 mg twice daily for 10 days) for the treatment of COVID-19 (AI). Other Antiviral Drugs The Panel recommends against using the following drugs to treat COVID-19, except in a clinical trial: The combination of hydroxychloroquine plus azithromycin (AIII), because of the potential for toxicities. Lopinavir/ritonavir (AI) or other HIV protease inhibitors (AIII), because of unfavorable pharmacodynamics and because clinical trials have not demonstrated a clinical benefit in patients with COVID-19.
Rating of Recommendations: A = Strong; B = Moderate; C = Optional Rating of Evidence: I = One or more randomized trials with clinical outcomes and/or validated laboratory endpoints; II = One or more well-designed, nonrandomized trials or observational cohort studies; III = Expert opinion

Antiviral Therapy

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication leads to many of the clinical manifestations of COVID-19. Antiviral therapies are being investigated for the treatment of COVID-19. These drugs inhibit viral entry (via the angiotensin-converting enzyme 2 [ACE2] receptor and transmembrane serine protease 2 [TMPRSS2]), viral membrane fusion and endocytosis, or the activity of the SARS-CoV-2 3-chymotrypsin-like protease (3CLpro) and the RNA-dependent RNA polymerase.¹ Because viral replication may be particularly active early in the course of COVID-19, antiviral therapy may have the greatest impact before the illness progresses into the hyperinflammatory state that can characterize the later stages of disease, including critical illness.² For this reason, understanding the role of antivirals in treating mild, moderate, severe, and critical illness is necessary to optimize treatment for people with COVID-19.

The following sections describe the underlying rationale for using different antiviral medications, provide the Panel’s recommendations for their roles in treating COVID-19, and summarize the existing clinical trial data. Additional antiviral therapies will be added to this section of the guidelines as new evidence emerges.

References

Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a review. JAMA. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32282022.
Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: a clinical-therapeutic staging proposal. J Heart Lung Transplant. 2020;39(5):405-407. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32362390

Potential Antiviral Drugs Under Evaluation for the Treatment of COVID-19

Remdesivir

Recommendation for Prioritizing Limited Supplies of Remdesivir

Recommendation for Patients with Mild or Moderate COVID-19

Recommendation for Patients with COVID-19 Who Are on Supplemental Oxygen but Who Do Not Require High-Flow Oxygen, Noninvasive or Invasive Mechanical Ventilation, or ECMO

Recommendation for Patients with COVID-19 Who Require High-Flow Oxygen, Noninvasive Ventilation, Mechanical Ventilation, or ECMO

Duration of Therapy for Patients Who Have Not Shown Clinical Improvement After 5 Days of Therapy

Chloroquine or Hydroxychloroquine

Other Antiviral Drugs

Antiviral Therapy

References