Nirmatrelvir/ritonavir for patients with SARS-CoV-2 infection and impaired kidney function during the Omicron surge

Yan et al., Frontiers in Pharmacology, doi:10.3389/fphar.2023.1147980

Mar 2023

Retrospective 195 patients with impaired kidney function in China, showing lower combined mortality/ICU/cardiovascular events, and improved viral clearance with paxlovid.

Confounding by contraindication. Hoertel et al. find that over 50% of patients that died had a contraindication for the use of Paxlovid Hoertel. Retrospective studies that do not exclude contraindicated patients may significantly overestimate efficacy.

Black box warning. The FDA notes that "severe, life-threatening, and/or fatal adverse reactions due to drug interactions have been reported in patients treated with paxlovid" FDA.

1. FDA, Fact sheet for healthcare providers: emergency use authorization for paxlovid, www.fda.gov/media/155050/download.fda.gov.

2. Hoertel et al., Prevalence of Contraindications to Nirmatrelvir-Ritonavir Among Hospitalized Patients With COVID-19 at Risk for Progression to Severe Disease, JAMA Network Open, doi:10.1001/jamanetworkopen.2022.42140.jamanetwork.com, doi.org.

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risk of death, 31.2% lower, RR 0.69, p = 0.50, treatment 7 of 73 (9.6%), control 17 of 122 (13.9%), NNT 23.

mortality/ICU/cardiovascular events, 44.0% lower, HR 0.56, p = 0.04, treatment 73, control 122, adjusted per study, multivariable, model 2, primary outcome.

risk of ICU admission, 13.9% lower, RR 0.86, p = 0.61, treatment 17 of 73 (23.3%), control 33 of 122 (27.0%), NNT 27.

hospitalization time, 8.6% lower, relative time 0.91, p = 0.03, treatment 73, control 122.

time to viral-, 61.5% lower, relative time 0.38, p = 0.001, treatment 73, control 122.

risk of no viral clearance, 73.0% lower, HR 0.27, p < 0.001, treatment 73, control 122, adjusted per study, inverted to make HR<1 favor treatment, viral shedding, multivariable, model 2.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Yan et al., 22 Mar 2023, retrospective, placebo-controlled, China, peer-reviewed, median age 74.0, 10 authors, study period 1 April, 2022 - 30 June, 2022. Contact: shan_mou@shsmu.edu.cn, guleyi@aliyun.com, monsoon585@foxmail.com.

This Paper Paxlovid All

Nirmatrelvir/ritonavir for patients with SARS-CoV-2 infection and impaired kidney function during the Omicron surge

Jiayi Yan, Hong Cai, Jieying Wang, Mingli Zhu, Ping Li, Peiying Li, Bin Wu, Xiajing Che, Leyi Gu, Shan Mou

Frontiers in Pharmacology, doi:10.3389/fphar.2023.1147980

Background: Nirmatrelvir/ritonavir has demonstrated effectiveness in high-risk patients with coronavirus disease 2019 . However, investigations on the efficacy and safety of nirmatrelvir/ritonavir in patients with kidney dysfunction are limited. Methods: Data were collected from the patients admitted to a COVID-19 referral center in Shanghai, China. Patients were at least 18 years of age and had a baseline estimated glomerular filtration rate (eGFR) of <60 ml/min/1•73 m 2 . The primary endpoint was a composite of all-cause mortality, intensive care unit admission, or cardiovascular events. The secondary endpoint was viral shedding. Results: Among the 195 participants, 73 received nirmatrelvir/ritonavir. A lower risk of the primary endpoint was observed in nirmatrelvir/ritonavir recipients compared with non-recipients [adjusted HR 0.56 (95% CI: 0.32-0.96); p = 0.035]. Nirmatrelvir/ritonavir recipients experienced a shorter duration of viral shedding ; p < 0.001) and faster viral load clearance versus non-recipients. Among the nirmatrelvir/ritonavir users, earlier initiation of nirmatrelvir/ritonavir within 5 days since COVID-19 diagnosis was related with shorter viral shedding time ; p < 0.001) compared to late initiation. No patients reported serious adverse events during treatment. Conclusion: Our findings support the early initiation of nirmatrelvir/ritonavir for high-risk patients with impaired kidney function. This could improve patient outcomes and shorten the viral shedding period.

Ethics statement The studies involving human participants were reviewed and approved by Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. The ethics committee waived the requirement of written informed consent for participation. Author contributions JY, SM, and LG designed the study. JY, HC, and JW analyzed the data and revised the manuscript. JY and SM drafted and edited the final manuscript. All authors took part in collecting and verifying the Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Supplementary material The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphar.2023.1147980/ full#supplementary-material

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