CLINICAL QUESTION

In patients who are fully vaccinated and have a risk factor or in those who are unvaccinated without a risk factor who have COVID-19 and are symptomatic, does nirmatrelvir/ritonavir (Paxlovid) reduce the duration of symptoms or the likelihood of hospitalization?

BOTTOM LINE

Mortality and hospitalization rates due to COVID-19 have fallen since the beginning of the pandemic because of a combination of past infection, vaccination, and improved treatments. The 1% rate of hospitalization in this study is consistent with the hospitalization rate in a series of 19,456 outpatients with the Omicron variant. Although there was a numerical reduction in hospitalizations with treatment in the current study, it was not statistically significant. Even if it were significant, the number needed to treat (100) would be relatively high. (Level of Evidence = 1b)

SYNOPSIS

Nirmatrelvir/ritonavir was shown in a randomized trial to reduce hospitalization by 89% and death by 86% in patients who were unvaccinated and had at least one risk factor for severe disease when the ancestral variant of SARS-CoV-2 was predominant. But it is important that drugs be evaluated in the correct target population, which now includes patients who have been vaccinated and are sick with the Omicron variant. This industry-sponsored study enrolled two groups of patients: (1) fully vaccinated adults with symptomatic, confirmed infection with SARS-CoV-2 and at least one risk factor for severe disease; and (2) unvaccinated adults with a symptomatic infection and no risk factors. Later in the trial, the authors included patients at average risk who had not received a vaccine in the past 12 months.