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0 0.5 1 1.5 2+ Mortality 15% Improvement Relative Risk Ventilatory support -0% ICU admission 12% Molnupiravir  Cheng et al.  EARLY TREATMENT Is early treatment with molnupiravir beneficial for COVID-19? Retrospective 9,938 patients in China Lower mortality with molnupiravir (p=0.0025) Cheng et al., Kidney Int. Reports, Feb 2024 Favors molnupiravir Favors control

Effectiveness of molnupiravir and nirmatrelvir–ritonavir in CKD patients with COVID-19

Cheng et al., Kidney International Reports, doi:10.1016/j.ekir.2024.02.009
Feb 2024  
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Retrospective emulated target trial of hospitalized COVID-19 patients with chronic kidney disease in Hong Kong showing lower mortality with molnupiravir and paxlovid treatment. No significant reduction was found in ICU admission or ventilatory support.
Notably, there is no estimated benefit for ventilatory support, the outcome most directly related to severe COVID-19.
The very large difference in vaccine uptake suggests major confounding issues, for example treatment decisions based on vaccine uptake, or confounding by time where control patients are more likely from earlier periods with lower vaccine uptake, which may also correspond to more dangerous variants.
Concerns have been raised that the mutagenic mechanism of action may create dangerous variants or cause cancer Chamod, Hadj Hassine, Huntsman, Marikawa, Swanstrom, Waters, Zhou, Zibat. Multiple analyses have identified variants potentially created by molnupiravir Fountain-Jones, Kosakovsky Pond, Sanderson,
Study covers molnupiravir and paxlovid.
risk of death, 14.6% lower, HR 0.85, p = 0.003, treatment 4,146, control 5,792.
ventilatory support, 0.1% higher, HR 1.00, p = 1.00, treatment 4,146, control 5,792.
risk of ICU admission, 12.5% lower, HR 0.88, p = 0.52, treatment 4,146, control 5,792.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Cheng et al., 9 Feb 2024, retrospective, China, peer-reviewed, 11 authors. Contact:,
This PaperMolnupiravirAll
Effectiveness of molnupiravir and nirmatrelvir–ritonavir in CKD patients with COVID-19.
Franco Wing Tak Cheng, Vincent Ka Chun Yan, Eric Yuk Fai Wan, Celine Sze Ling Chui, Francisco Tsz Tsun Lai, Carlos King Ho Wong, Xue Li, Irene Ran Zhang, Sydney Chi Wai Tang, Ian Chi Kei Wong, Esther Wai Yin Chan
Kidney International Reports, doi:10.1016/j.ekir.2024.02.009
Introduction Even with effective vaccines, patients with CKD have a higher risk of hospitalization and death subsequent to COVID-19 infection compared with those without CKD. Molnupiravir and nirmatrelvir-ritonavir have been approved for emergency use, but their effectiveness for the CKD population is still unknown. This study was conducted to determine the effectiveness of these drugs in reducing mortality and severe COVID-19 in the CKD population. Methods This was a target trial emulation study using electronic health databases in Hong Kong. Patients with CKD aged 18 years or older who were hospitalized with COVID-19 were included. The per-protocol average treatment effect among COVID-19 oral antiviral initiators, including all-cause mortality, ICU admission, and ventilatory support within 28 days, were compared to non-initiators. Results Antivirals have been found to lower the risk of all-cause mortality, with molnupiravir at a hazard ratio (HR) of 0.85 [95% CI, 0.77 to 0.95] and nirmatrelvir-ritonavir at an HR of 0.78 [CI, 0.60 to 1.00]. However, they do not significantly reduce the risk of ICU admission (molnupiravir: HR, 0.88 [CI, 0.59 to 1.30]; nirmatrelvir-ritonavir: HR, 0.86 [CI, 0.56 to 1.32]) or ventilatory support (molnupiravir: HR, 1.00 [CI, 0.76 to 1.33]; nirmatrelvir-ritonavir: HR, 1.01 [CI, 0.74 to 1.37]). There was a greater risk reduction in males and those with higher Charlson Comorbidity Index. The nirmatrelvir-ritonavir trial also showed reduced risk for those who had antiviral treatment and received three or more vaccine doses. Conclusion Both molnupiravir and nirmatrelvir-ritonavir reduced mortality rates for hospitalized COVID-19 patients with CKD.
Supplementary Material STROBE statement (PDF) Supplementary Table S1 Target trial specification and emulation using observational data (PDF) Supplementary Table S2 . Baseline and post-assignment covariates for the construction of inverse probability weights (PDF) Supplementary Table S3 . Survival Probability for Outcomes in COVID-19 Oral Antiviral Initiators Compared With Non-initiators (PDF) Supplementary information is available at KI Report's website. J o u r n a l P r e -p r o o f
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