Nirmatrelvir-Ritonavir and COVID-19 Mortality and Hospitalization Among Patients With Vulnerability to COVID-19 Complications

JAMA Netw Open. 2023 Oct 2;6(10):e2336678. doi: 10.1001/jamanetworkopen.2023.36678.


Importance: Postmarket analysis of individuals who receive nirmatrelvir and ritonavir (Paxlovid [Pfizer]) is essential because they differ substantially from individuals included in published clinical trials.

Objective: To examine the association of nirmatrelvir and ritonavir with prevention of death or admission to hospital in individuals with different risks of complications from COVID-19 infection.

Design, setting, and participants: This is a cohort study of adult patients in British Columbia, Canada, between February 1, 2022, and February 3, 2023. Patients were eligible if they belonged to 1 of 4 higher-risk groups of individuals who received priority for COVID-19 vaccination. Two groups included clinically extremely vulnerable (CEV) people who were severely (CEV1) or moderately immunocompromised (CEV2). CEV3 individuals were not immunocompromised but had medical conditions associated with a high risk for complications from COVID-19. A fourth expanded eligibility (EXEL) group was added to allow wider access to nirmatrelvir and ritonavir for certain other higher-risk individuals who were not in a CEV group, such as those older than 70 years who were unvaccinated.

Exposures: Patients with COVID-19 who received nirmatrelvir and ritonavir were matched to patients in the same vulnerability group; who were of the same sex, age, and propensity score for nirmatrelvir and ritonavir treatment; and who were also infected within 1 month of the individual treated with nirmatrelvir and ritonavir.

Main outcomes and measures: The primary outcome was death from any cause or emergency hospitalization with COVID-19 within 28 days.

Results: There were 6866 individuals included in the study, of whom 3888 (56.6%) were female and whose median (IQR) age was 70 (57-80) years. Compared with unexposed controls, treatment with nirmatrelvir and ritonavir was associated with statistically significant relative reductions in the primary outcome in the CEV1 group (560 patients; risk difference [RD], -2.5%, 95% CI, -4.8% to -0.2%) and the CEV2 group (2628 patients; RD, -1.7%; 95% CI, -2.9% to -0.5%). In the CEV3 group, the RD was -1.3%, but the findings were not statistically significant (2100 patients; 95% CI, -2.8% to 0.1%). In the EXEL group, treatment was associated with higher risk of the outcome (RD, 1.0%), but the findings were not statistically significant (1578 patients; 95% CI, -0.9% to 2.9%).

Conclusions and relevance: In this cohort study of 6866 individuals in British Columbia, nirmatrelvir and ritonavir treatment was associated with reduced risk of COVID-19 hospitalization or death in CEV individuals, with the greatest benefit observed in severely immunocompromised individuals. No reduction in the primary outcome was observed in lower-risk individuals, including those aged 70 years or older without serious comorbidities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • British Columbia / epidemiology
  • COVID-19 Drug Treatment
  • COVID-19 Vaccines
  • COVID-19*
  • Cohort Studies
  • Female
  • Hospitalization
  • Humans
  • Male
  • Ritonavir* / therapeutic use


  • nirmatrelvir and ritonavir drug combination
  • Ritonavir
  • COVID-19 Vaccines