Outpatient Treatment of Confirmed COVID-19 in Symptomatic Adults: Living, Rapid Practice Points From the American College of Physicians (Version 3)

The American College of Physicians (ACP) maintains living, rapid practice points on antiviral treatment in the outpatient setting for COVID-19.

The Population Health and Medical Science Committee (PHMSC) developed this version 3 based on evidence from a focused update of a living, rapid review conducted by the ACP Center for Evidence Reviews at Cochrane Austria. This version addresses the SARS-CoV-2 Omicron variant and reaffirms previous practice points on the use of antiviral treatments of confirmed COVID-19 in unvaccinated or vaccinated and symptomatic patients in the outpatient setting.

Consider nirmatrelvir-ritonavir combination therapy to treat symptomatic patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 days of the onset of symptoms and at a high risk for progressing to severe disease.

Consider molnupiravir to treat symptomatic patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 days of the onset of symptoms and at a high risk for progressing to severe disease.

Do not use ivermectin to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting.

Do not use sotrovimab to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting.

The PHMSC is retiring this topic from living status considering that this update and previous surveillance have not yielded important changes to the practice points.

Published by Annals of internal medicine, 2026. The guideline itself is at the source linked here.

doi.org/10.7326/ANNALS-25-03766