Oral Nirmatrelvir and Ritonavir in Nonhospitalized Vaccinated Patients With Coronavirus Disease 2019

Background: Treatment of coronavirus disease 2019 (COVID-19) with nirmatrelvir plus ritonavir (NMV-r) in high-risk nonhospitalized unvaccinated patients reduced the risk of progression to severe disease. However, the potential benefits of NMV-r among vaccinated patients are unclear.

Methods: We conducted a comparative retrospective cohort study using the TriNetX research network. Patients ≥18 years of age who were vaccinated and subsequently developed COVID-19 between 1 December 2021 and 18 April 2022 were included. Cohorts were developed based on the use of NMV-r within 5 days of diagnosis. The primary composite outcome was all-cause emergency room (ER) visit, hospitalization, or death at a 30-day follow-up. Secondary outcomes included individual components of primary outcomes, multisystem symptoms, COVID-19-associated complications, and diagnostic test utilization.

Results: After propensity score matching, 1130 patients remained in each cohort. A primary composite outcome of all-cause ER visits, hospitalization, or death in 30 days occurred in 89 (7.87%) patients in the NMV-r cohort compared with 163 (14.4%) patients in the non-NMV-r cohort (odds ratio: .5; 95% confidence interval: .39-.67; P < .005) consistent with 45% relative risk reduction. A significant reduction in multisystem symptom burden and subsequent complications, such as lower respiratory tract infection, cardiac arrhythmia, and diagnostic radiology testing, were noted in NMV-r-treated patients. There was no apparent increase in serious complications between days 10 and 30.

Conclusions: Treatment with NMV-r in nonhospitalized vaccinated patients with COVID-19 was associated with a reduced likelihood of ER visits, hospitalization, or death. Complications and overall resource utilization were also decreased.