Effectiveness and Safety of Nirmatrelvir-Ritonavir in Hospitalized Patients with COVID-19: A Two-center Cohort Study

Abstract Background: On May 25, 2023, the antiviral medication nirmatrelvir-ritonavir received complete FDA authorization, making it the first oral antiviral to treat mild-to-moderate COVID-19 in high-risk patients for progression to severe COVID-19. While the effect of nirmatrelvir-ritonavir is endorsed in non-hospitalized patients, its effectiveness in hospitalized patients remains uncertain. This study aimed to investigate the effectiveness of nirmatrelvir-ritonavir in treating COVID-19 among hospitalized patients. Materials and Methods: A retrospective observational cohort study involving two centers was carried out in the Makkah and Jazan regions of Saudi Arabia from January 2023 to August 2023. The study included adult patients hospitalized who were diagnosed with COVID-19. Patients were classified into two sub-cohorts based on their nirmatrelvir-ritonavir treatment status within five days following COVID-19 detection. The primary outcome of the study was the in-hospital mortality. The secondary outcomes included ICU admissions, mechanical ventilation needs, acute kidney injury (AKI), and liver injury during hospital stay. Results: A total of 234 patients admitted with COVID-19 were screened, while 74 were included in the study. The in-hospital mortality showed no significant difference between the groups in the crude analysis (10% vs. 14%; P = 0.64). This finding was consistent in the regression analysis after adjusting for potential confounders (aOR = 2.95; 95% CI: 0.45–19.52; P = 0.26). The nirmatrelvir-ritonavir patients (treatment group) had higher odds of COVID-19 complications; however, this difference was not statistically significant (aOR=2.62; 95% CI:0.44–15.76; P = 0.29). Admission to the ICU was lower in the treatment group but did not achieve a statistical difference. There were no significant differences in other complications during hospitalization between the two groups. Conclusion: This study highlights that nirmatrelvir-ritonavir use in hospitalized COVID-19 patients did not result in improved hospital mortality or reduction in COVID-19 related complications.