Oral Nirmatrelvir and Ritonavir in Nonhospitalized Vaccinated Patients With Coronavirus Disease 2019 (COVID-19)

In this observational analysis of real-world data, treatment with nirmatrelvir plus ritonavir in nonhospitalized vaccinated patients at high risk of disease progression was associated with a significantly reduced likelihood of emergency room visits, hospitalization, or death, with no apparent increase in serious complications between days 10 and 30. 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.

Automated summary

In this observational analysis, treatment with nirmatrelvir plus ritonavir in nonhospitalized vaccinated patients at high risk of disease progression was associated with a significantly reduced likelihood of emergency room visits, hospitalization, or death between days 10 and 30, with no apparent increase in serious complications.