Effective antiviral regimens to reduce COVID-19 hospitalizations: a systematic comparison of randomized controlled trials

ABSTRACT

During pandemics, out-of-hospital treatments reduce the health system burden. Controversies persist regarding the best treatment options for COVID-19 outpatients at risk for hospitalization. We assembled data from 47 randomized controlled trials investigating 51 distinct interventions in more than 60,000 outpatients until October 2022 with the endpoint of hospitalization. These trials, largely performed in unvaccinated cohorts during pre-Omicron waves, mostly targeted populations with at least one risk factor for COVID-19 hospitalization. Grouping by class, the COVID-19 convalescent plasma (CCP) (OR=0.69 [95% CI=0.53 to 0.9]), anti-Spike monoclonal antibodies (OR=0.32 [95% CI=0.24-0.42]) and small molecule antivirals (OR=0.57 [95% CI=0.3-1.09]) each had comparable efficacy for hospital relative risk reduction dependent on intervention dose and timing. Repurposed drugs had lower efficacy. The recent Omicron sublineages (XBB and BQ.1.1) in vitro resistance to monoclonal antibodies suggests a pressing need to reevaluate CCP recommendations for COVID-19 outpatients at risk for hospitalization, especially in constrained medical resource settings.