Journal Article

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

Lam, Man Lok, Yip, Edmond Tsz Fung, Wong, Eliza Lai Yi, Chan, Sunny Ching Long, Lee, Shi Yeow, Wai, Abraham Ka Chung, Rainer, Timothy Hudson, Lee, Teddy Tai Loy, Luk, Luke Yik Fung, Tong, Chak Kwan, Jiang, Ting Ting, Yamamoto, Tafu, Wong, Man Sing, Lyu, Alex Chang-Hao, So, Kevin Wang Leong, Tsui, Omar Wai Kiu, Chan, Crystal Ying, Ho, Joshua Wing Kei

2025

Overview

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

• Publisher: JMIR Publications,JMIR Publications Inc
• Subject: Aged / Aged, 80 and over / Antibiotics / Antiviral Agents - therapeutic use / Antiviral drugs / Cohort analysis / COVID-19 / COVID-19 - mortality / COVID-19 Drug Treatment / COVID-19 Vaccination / Cytidine - analogs & derivatives / Cytidine - therapeutic use / Disease / Female / Fungal infections / Health Services Research / Hong Kong - epidemiology / Hospital Mortality / Hospitals / Humans / Hydroxylamines - therapeutic use / Hygiene and Infection Prevention / Infectious Diseases (non-STD/STI) / Kidneys / Length of stay / Liver / Male / Middle Aged / Mortality / Mortality risk / Multimedia / Older people / Original Paper / Patients / Proline - analogs & derivatives / Proline - therapeutic use / Respiratory failure / Respiratory Medicine / Retrospective Studies / Review boards / Ritonavir / Ritonavir - therapeutic use / Sepsis / Sepsis - drug therapy / Sepsis - virology / Shock (Circulatory) / Treatment Outcome / Viral infections