Outpatient Treatment of Confirmed COVID-19: A Living, Rapid Review for the American College of Physicians

Clinicians and patients want to know the benefits and harms of outpatient treatment options for SARS-CoV-2 infection. To assess the benefits and harms of 12 different COVID-19 treatments in the outpatient setting. Epistemonikos COVID-19 L·OVE Platform, searched on 4 April 2022. Two reviewers independently screened abstracts and full texts against a priori-defined criteria. Randomized controlled trials (RCTs) that compared COVID-19 treatments in adult outpatients with confirmed SARS-CoV-2 infection were included. One reviewer extracted data and assessed risk of bias and certainty of evidence (COE). A second reviewer verified data abstraction and assessments. The 26 included studies collected data before the emergence of the Omicron variant. Nirmatrelvir-ritonavir and casirivimab-imdevimab probably reduced hospitalizations (1% vs. 6% [1 RCT] and 1% vs. 4% [1 RCT], respectively; moderate COE). Nirmatrelvir-ritonavir probably reduced all-cause mortality (0% vs. 1% [1 RCT]; moderate COE), and regdanvimab probably improved recovery (87% vs. 72% [1 RCT]; moderate COE). Casirivimab-imdevimab reduced time to recovery by a median difference of 4 days (10 vs. 14 median days [1 RCT]; high COE). Molnupiravir may reduce all-cause mortality, sotrovimab may reduce hospitalization, and remdesivir may improve recovery (low COE). Lopinavir-ritonavir and azithromycin may have increased harms, and hydroxychloroquine may result in lower recovery rates (low COE). Other treatments had insufficient evidence or no statistical difference in efficacy and safety versus placebo. Many outcomes had few events and small samples. Some antiviral medications and monoclonal antibodies may improve outcomes for outpatients with mild to moderate COVID-19. However, the generalizability of the findings to the currently dominant Omicron variant is limited. American College of Physicians. (PROSPERO: CRD42022323440).