Nirmatrelvir–ritonavir (Paxlovid [Pfizer]) is used as first-line therapy for nonhospitalized persons with Covid-191 on the basis of the results of the Evaluation of Protease Inhibition for Covid-19 in High-Risk Patients (EPIC-HR) trial, which showed that this medication reduced the risk of hospitalization or death by 88%.2 The EPIC-HR trial enrolled adults who had not received a SARS-CoV-2 vaccine and who were at high risk for progression to severe Covid-19. Given those results, the question arose as to whether nirmatrelvir–ritonavir conferred a benefit in persons who had been vaccinated or who did not have risk factors for severe disease. [New England Journal of Medicine]

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