Clinical real-world effectiveness of nirmatrelvir/ritonavir for the treatment of SARS-CoV-2 infection: A meta-analysis

Abstract

Abstract Background: According to the Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients (EPIC-HR) study, compared with a placebo, nirmatrelvir/ritonavir significantly reduced the risk of coronavirus disease 2019 (COVID-19)-related hospitalization or mortality in unvaccinated patients. The Delta variant was the most prevalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant among all treatment recipients in the EPIC-HR study. The Omicron variant is less pathogenic than the Delta variant. The efficacy of nirmatrelvir/ritonavir in partially or fully immunized patients with Omicron variant-related infections must be further evaluated. Objectives: The current meta-analysis aimed to evaluate the therapeutic efficacy of nirmatrelvir/ritonavir based on factors including hospitalization, all-cause mortality, and COVID-19 rebound in patients who were partially or fully immunized against COVID-19. Methods: This meta-analysis aimed to evaluate the therapeutic efficacy of nirmatrelvir/ritonavir based on factors including hospitalization, all-cause mortality, and COVID-19 rebound in patients who were partially or fully immunized against COVID-19. It included 26 studies that directly examined the clinical efficacy of nirmatrelvir/ritonavir versus placebo in adult patients with SARS-CoV-2 infection caused by the Omicron variant. The search criteria comprised keywords such as hospitalization, all-cause mortality, and COVID-19 rebound. Results: The all-cause mortality risk was reduced by 59% in patients aged ≥65 years. However, their hospitalization risk decreased by only 36%. The reduction in all-cause mortality and hospitalization risk was similar between patients with low and high COVID-19 vaccination coverage. Patients receiving nirmatrelvir/ritonavir had a higher incidence of COVID-19 rebound than those receiving a placebo. However, the hospitalization risk and all-cause mortality of adult patients with COVID-19 treated with nirmatrelvir/ritonavir reduced by 53% and 57%, respectively. Conclusion: The current meta-analysis of 26 studies indicates that adult patients with COVID-19 treated with nirmatrelvir/ritonavir reduced the risk of hospitalization by 53% and all-cause mortality by 57% compared to a placebo.