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Antiviral Drugs That Are Under Evaluation for the Treatment of COVID-19

Last Updated: October 9, 2020

Summary Recommendations
Summary Recommendations

There are no Food and Drug Administration-approved drugs for the treatment of COVID-19. In this section, 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 Table 2.

Remdesivir

The Remdesivir section of the Guidelines will be updated soon. See Therapeutic Management of Patients with COVID-19 for recommendations on using remdesivir with or without corticosteroids.

Recommendation for Prioritizing Limited Supplies of Remdesivir

  • Because remdesivir supplies are limited, the Panel recommends prioritizing remdesivir for use in hospitalized patients with COVID-19 who require supplemental oxygen but who do not require oxygen delivery through a high-flow device, noninvasive ventilation, invasive 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.

Recommendations for Patients with COVID-19 Who Require Supplemental Oxygen

For Patients Who Do Not Require Oxygen Delivery Through a High-Flow Device, Noninvasive Ventilation, 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 delivery of oxygen through a high-flow device, noninvasive ventilation, invasive mechanical ventilation, or ECMO, the course of remdesivir should be completed.

For Patients Who Require Oxygen Delivery Through a High-Flow Device, Noninvasive Ventilation, Invasive 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 With or Without Azithromycin

  • The Panel recommends against the use of chloroquine or hydroxychloroquine with or without azithromycin for the treatment of COVID-19 in hospitalized patients (AI).
  • In nonhospitalized patients, the Panel recommends against the use of chloroquine or hydroxychloroquine with or without azithromycin for the treatment of COVID-19, except in a clinical trial (AI).
  • The Panel recommends against the use of high-dose chloroquine (600 mg twice daily for 10 days) for the treatment of COVID-19 (AI).

Lopinavir/Ritonavir and Other HIV Protease Inhibitors

  • The Panel recommends against using lopinavir/ritonavir (AI) or other HIV protease inhibitors (AIII) to treat COVID-19, except in a clinical trial.

Ivermectin

  • The Panel recommends against the use of ivermectin for the treatment of COVID-19, except in a clinical trial (AIII).
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

Because 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, it is necessary to understand the role of antivirals in treating mild, moderate, severe, and critical illness in order 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 using these medications to treat 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

  1. Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a review. JAMA. 2020;323(18):1824-1836. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32282022.
  2. 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.