Effectiveness of Antivirals Nirmatrelvir-Ritonavir and Molnupiravir in Viral Sepsis: Retrospective Cohort Study.

BACKGROUND

Viral infections, including those leading to sepsis, are common but often overlooked in clinical practice, yet the treatment strategies for viral sepsis remain inadequately defined.

OBJECTIVE

This study aims to investigate the effectiveness of antivirals nirmatrelvir-ritonavir and molnupiravir in the treatment of culture-negative sepsis.

METHODS

This retrospective cohort study was conducted across public hospitals in Hong Kong. We included patients diagnosed with COVID-19 between February 22, 2022, and June 30, 2023, who had no secondary bacterial or fungal infections. Propensity score matching was used to assess the efficacy of the antivirals nirmatrelvir-ritonavir and molnupiravir in patient subgroups with or without organ dysfunction at hospital admission, including circulatory shock, respiratory failure, acute kidney injury, coagulopathy, acute liver impairment, a composite of all organ dysfunctions, or no organ dysfunction. Key outcomes were in-hospital mortality and length of stay, reported as hazard ratios (HR) and mean differences, respectively.

RESULTS

The study included 15,599 COVID-19 patients with a mean age of 75.1 (SD 15.9) years. Molnupiravir treatment was associated with a significantly lower risk of mortality in patients in both the presence of any organ dysfunction (HR 0.75, 95% CI 0.58 to 0.96) and without organ dysfunction (HR 0.29, 95% CI 0.15-0.56). Nirmatrelvir-ritonavir was associated with decreased mortality with respiratory failure (absolute risk difference: 9.5%, 95% CI 6.26-12.72) and without organ dysfunction (HR 0.17, 95% CI 0.05-0.56). Antivirals also reduced the length of hospital stay; nirmatrelvir-ritonavir reduced length of stay in respiratory failure by an average of 3.37 (95% CI 2.32-4.42) days, acute kidney injury by 7.25 (95% CI 2.97-11.52) days, and coagulopathy by 7.04 (95% CI 2.99-4.05) days. Molnupiravir reduced the length of stay in acute kidney injury by an average of 6.7 (95% CI 2.39-11.08) days and coagulopathy by 5.68 (95% CI 1.20-10.16) days.

CONCLUSIONS

Antivirals reduced mortality among hospitalized COVID patients, with the greatest reduction observed in patients without organ dysfunction. Antivirals were also effective in reducing the length of hospital stay.