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Nirmatrelvir/ritonavir (N/R; Paxlovid) has been authorized for treatment of high-risk nonhospitalized patients with COVID-19 based on the EPIC-HR study (NEJM JW Infect Dis Apr 2022 and N Engl J Med 2022 Feb 16; [e-pub]), which showed an 88% reduction in hospitalization and death; however, EPIC-HR was conducted in unvaccinated individuals during a time when the Delta variant predominated. Now, investigators have assessed N/R for patients aged 40 and older in a large Israeli healthcare organization during the Omicron era.
In this retrospective cohort study, outcomes were compared in 3902 patients who received N/R versus 105,352 who did not. Overall, about 80% had previous immunity (vaccination, prior infection, or both). Key findings were:
Among patients aged 65 and older, hospitalization was less likely in the treated group (hazard ratio, 0.27). There was benefit regardless of patients' previous immunity status.
Among patients aged 40–64, hospitalization rates were similar in the treated and untreated groups (hazard ratio, 0.74).
Arbel R et al. Nirmatrelvir use and severe Covid-19 outcomes during the Omicron surge. N Engl J Med 2022 Aug 24; [e-pub]. (https://doi.org/10.1056/NEJMoa2204919)
Comment
Recent months have seen vigorous discussion regarding who should receive nirmatrelvir. This debate was prompted in part by a preprint of this study — which does not find clear-cut benefit in younger people (most of whom had previous immunity) — as well as a press release reporting the results of the EPIC-SR study, which found a nonsignificant reduction in hospitalization and death in lower-risk people (a mix of individuals without risk factors and those who had been vaccinated). My own view is that, just as there's a gradient of risk for progression, there will be a corresponding gradient of benefit from treatment, with higher-risk patients deriving more benefit. I recommend nirmatrelvir for older people regardless of vaccination status. For younger people who are vaccinated and boosted, I recommend nirmatrelvir if they have conditions that put them at substantial risk for progression, including obesity, heart or lung disease, immunosuppression, and other high-risk conditions.