Background: Clinicians and patients want to know the benefits and harms of outpatient treatment options for the Omicron variant of SARS-CoV-2.
Purpose: To assess the benefits and harms of 22 different COVID-19 treatments.
Data sources: The Epistemonikos COVID-19 L·OVE platform, the iSearch COVID-19 portfolio, and the World Health Organization (WHO) COVID-19 Research Database from 26 November 2021 to 2 March 2023.
Study selection: Two reviewers independently screened abstracts and full texts against a priori-defined criteria.
Data extraction: One reviewer extracted the data and assessed the risk of bias and certainty of evidence (COE). A second reviewer verified the data abstraction and assessments.
Data synthesis: Two randomized controlled trials and 6 retrospective cohort studies were included. Nirmatrelvir-ritonavir was associated with a reduction in hospitalization due to COVID-19 (for example, 0.7% vs. 1.2%; moderate COE) and all-cause mortality (for example, <0.1% vs. 0.2%; moderate COE). Molnupiravir led to a higher recovery rate (31.8% vs. 22.6%; moderate COE) and reduced time to recovery (9 vs. 15 median days; moderate COE) but had no effect on all-cause mortality (0.02% vs. 0.04%; moderate COE) and the incidence of serious adverse events (0.4% vs. 0.3%; moderate COE). Ivermectin had no effect on time to recovery (moderate COE) and resulted in no difference in adverse events compared with placebo (low COE). Sotrovimab resulted in no difference in all-cause mortality compared with no treatment (low COE). No eligible studies for all other treatments of interest were identified.
Limitation: Evidence for nirmatrelvir-ritonavir and sotrovimab is based on nonrandomized studies only.
Conclusion: Nirmatrelvir-ritonavir and molnupiravir probably improve outcomes for outpatients with mild to moderate COVID-19.
Primary funding source: American College of Physicians. (PROSPERO: CRD42023406456).