LAUSR

Key Points Question Is treatment with nirmatrelvir in the acute phase of SARS-CoV-2 infection associated with a lower risk of post–COVID-19 condition (PCC)? Findings In this cohort study of 281 793 people with SARS-CoV-2 infection who had at least 1 risk factor for progression to severe COVID-19 illness, compared with 246 076 who had no treatment, nirmatrelvir use in the acute phase (n = 35 717) was associated with reduced risk of PCC, including reduced risk of 10 of 13 post–acute sequelae in various organ systems, as well as reduced risk of post–acute death and post–acute hospitalization. Nirmatrelvir was associated with reduced risk of PCC in people who were unvaccinated, vaccinated, and boosted, and in people with primary SARS-CoV-2 infection and reinfection. Meaning In people with SARS-CoV-2 infection and at least 1 risk factor for progression to severe COVID-19 illness, treatment with nirmatrelvir during the acute phase of COVID-19 was associated with reduced risk of PCC.