How Effective Is Nirmatrelvir/Ritonavir in Vaccinated Persons with COVID-19?

(NEJM) Preferred therapies for mild-to-moderate COVID-19 include a 3-day intravenous course of remdesivir or nirmatrelvir/ritonavir (Paxlovid). The only published randomized trial of nirmatrelvir/ritonavir was conducted prior to widespread vaccination (N Engl J Med 2022; 386:1397. opens in new tab). Thus, clinicians need further information on the effectiveness of this treatment in more-heavily immune populations. Investigators conducted a retrospective cohort study involving 44,551 patients aged ≥50 (of whom 90% had received at least 3 doses of vaccine) eligible to receive nirmatrelvir/ritonavir. The 28% of patients who received nirmatrelvir/ritonavir had more comorbidities and were more likely to be vaccinated. Black and Hispanic patients — but not patients from disadvantaged neighborhoods — were less likely to receive nirmatrelvir/ritonavir. Hospitalization or death within 28 days of diagnosis occurred in 69 treated patients (0.55%) and 310 untreated patients (0.97%). Adjusted risk ratios for hospitalization (0.60) and death (0.29) favored treatment, particularly in those who were unvaccinated or were >20 weeks from their last immunization. No difference in relative benefit was observed between patients older or younger than 65.