• Kevin L Schwartz, Jun Wang, Mina Tadrous, Bradley J Langford, Nick Daneman, Valerie Leung, Tara Gomes, Lindsay Friedman, Peter Daley, and Kevin A Brown.
• Public Health Ontario (Schwartz, Wang, Langford, Daneman, Leung, Friedman, Brown); ICES Central (Schwartz, Wang, Tadrous, Daneman, Gomes, Brown); Leslie Dan Faculty of Pharmacy (Tadrous, Gomes) and Dalla Lana School of Public Health (Langford, Brown, Schwartz), University of Toronto; Toronto East Health Network (Leung); Li Ka Shing Knowledge Institute of St. Michael's Hospital (Gomes); Sunnybrook Health Sciences Centre (Daneman), Toronto, Ont.; Memorial University (Daley), St. John's, NL Kevin.schwartz@oahpp.ca.
• CMAJ. 2023 Feb 13; 195 (6): E220E226E220-E226.

BackgroundA randomized controlled trial involving a high-risk, unvaccinated population that was conducted before the Omicron variant emerged found that nirmatrelvir-ritonavir was effective in preventing progression to severe COVID-19. Our objective was to evaluate the effectiveness of nirmatrelvir-ritonavir in preventing severe COVID-19 while Omicron and its subvariants predominate.MethodsWe conducted a population-based cohort study in Ontario that included all residents who were older than 17 years of age and had a positive polymerase chain reaction test for SARS-CoV-2 between Apr. 4 and Aug. 31, 2022. We compared patients treated with nirmatrelvir-ritonavir with patients who were not treated and measured the primary outcome of hospital admission from COVID-19 or all-cause death at 1-30 days, and a secondary outcome of all-cause death. We used weighted logistic regression to calculate weighted odds ratios (ORs) with confidence intervals (CIs) using inverse probability of treatment weighting (IPTW) to control for confounding.ResultsThe final cohort included 177 545 patients, 8876 (5.0%) who were treated with nirmatrelvir-ritonavir and 168 669 (95.0%) who were not treated. The groups were well balanced with respect to demographic and clinical characteristics after applying stabilized IPTW. We found that the occurrence of hospital admission or death was lower in the group given nirmatrelvir-ritonavir than in those who were not (2.1% v. 3.7%; weighted OR 0.56, 95% CI 0.47-0.67). For death alone, the weighted OR was 0.49 (95% CI 0.39-0.62). Our findings were similar across strata of age, drug-drug interactions, vaccination status and comorbidities. The number needed to treat to prevent 1 case of severe COVID-19 was 62 (95% CI 43-80), which varied across strata.InterpretationNirmatrelvir-ritonavir was associated with significantly reduced odds of hospital admission and death from COVID-19, which supports use to treat patients with mild COVID-19 who are at risk for severe disease.© 2023 CMA Impact Inc. or its licensors.

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