Should Patients with COVID-19 Who Are at Standard Risk Take Nirmatrelvir/Ritonavir?

U.S. National Institutes of Health guidelines currently recommend nirmatrelvir/ritonavir (Paxlovid) as first-line therapy for outpatients with COVID-19 who are at high risk for progressing to severe disease. This recommendation stems from the initial randomized trial of Paxlovid, which showed that the drug lowered risk for hospitalization and death among high-risk, unvaccinated adults (NEJM JW Gen Med Apr 15 2022 and N Engl J Med 2022; 386:1397). In subsequent observational trials, benefits have varied, depending on the patient population included.

Now, in a manufacturer-sponsored trial, researchers examined the effectiveness of Paxlovid among standard-risk patients. About 1300 adults (median age, 42) with symptomatic COVID-19 received 5-day courses of Paxlovid or placebo. Participants were fully vaccinated with at least one risk factor for severe disease (e.g., smoking, hypertension, obesity), or they had no risk factors and were unvaccinated (i.e., never vaccinated or no vaccine within the past 1 year). Fewer than 2% of patients had heart or lung disease, and only 5% were 65 or older.

The primary outcome — time to sustained alleviation of symptoms — did not differ between the Paxlovid and placebo groups. A secondary outcome (COVID-related hospitalization or death from any cause) occurred in 5 Paxlovid recipients and in 10 placebo recipients; this difference was not significant.