• Isolde Sommer, Andreea Dobrescu, Dominic Ledinger, Isabel Moser, Kylie Thaler, Emma Persad, Martin Fangmeyer, Robert Emprechtinger, Irma Klerings, and Gerald Gartlehner.
• Cochrane Austria, Department for Evidence-based Medicine and Evaluation, University for Continuing Education Krems (Danube University Krems), Krems, Austria (I.S., A.D., D.L., I.M., K.T., E.P., M.F., I.K.).
• Ann. Intern. Med. 2023 Jan 1; 176 (1): 9210492-104.

BackgroundClinicians and patients want to know the benefits and harms of outpatient treatment options for SARS-CoV-2 infection.PurposeTo assess the benefits and harms of 12 different COVID-19 treatments in the outpatient setting.Data SourcesEpistemonikos COVID-19 L·OVE Platform, searched on 4 April 2022.Study SelectionTwo 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.Data ExtractionOne reviewer extracted data and assessed risk of bias and certainty of evidence (COE). A second reviewer verified data abstraction and assessments.Data SynthesisThe 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.LimitationMany outcomes had few events and small samples.ConclusionSome 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.Primary Funding SourceAmerican College of Physicians. (PROSPERO: CRD42022323440).

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