Clinical characteristics and outcomes of hospitalized kidney transplant recipients with COVID-19 infection in China during the Omicron wave: a single-center cohort study
et al., Journal of Zhejiang University - SCIENCE B (Biomedicine & Biotechnology, doi:10.1631/jzus.B2300538, Jun 2024
Retrospective 324 hospitalized kidney transplant recipients with COVID-19 showing no significant benefit with molnupiravir, paxlovid, or azvudine. The study was conducted during the omicron wave in China between December 2022 and January 2023. Adjusted results are only provided for all antivirals combined, however the results are similar before and after adjustment. Multivariable Cox regression analysis for all antivirals combined showed an adjusted hazard ratio for mortality of 6.06, p=0.099. While adjustment includes factors related to baseline severity, there may be residual confounding by indication.
Resistance. Variants may be resistant to paxlovid1-8. Use may promote the emergence of variants that weaken host immunity and potentially contribute to long COVID9. Confounding by contraindication. Hoertel et al. find that over 50% of patients that died had a contraindication for the use of Paxlovid10. 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 paxlovid11. Kidney and liver injury. Studies show significantly increased risk of acute kidney injury12 and liver injury13.
Standard of Care (SOC) for COVID-19 in the study country,
China, is average with moderate efficacy for approved treatments14.
This study is excluded in the after exclusion results of meta
analysis:
unadjusted results with no group details.
Study covers molnupiravir, paxlovid, and azvudine.
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risk of death, 494.6% higher, RR 5.95, p < 0.001, treatment 35 of 148 (23.6%), control 7 of 176 (4.0%).
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| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
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Thomas et al., Nirmatrelvir-Resistant Mutations in SARS-CoV-2 Mpro Enhance Host Immune Evasion via Cleavage of NF-κB Essential Modulator, bioRxiv, doi:10.1101/2024.10.18.619137.
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Lv et al., 24 Jun 2024, retrospective, China, peer-reviewed, 10 authors, average treatment delay 14.0 days.
Clinical characteristics and outcomes of hospitalized kidney transplant recipients with COVID-19 infection in China during the Omicron wave: a single-center cohort study
doi:10.1631/jzus.B2300538
Background: Following the short-term outbreak of coronavirus disease 2019 in December 2022 in China, clinical data on kidney transplant recipients (KTRs) with COVID-19 are lacking. Methods: We conducted a single-center retrospective study to describe the clinical features, complications, and mortality rates of hospitalized KTRs infected with COVID-19 between Dec. 16, 2022 and Jan. 31, 2023. The patients were followed up until Mar. 31, 2023. Results: A total of 324 KTRs with COVID-19 were included. The median age was 49 years. The median time between the onset of symptoms and admission was 13 d. Molnupiravir, azvudine, and nirmatrelvir/ritonavir were administered to 67 (20.7%), 11 (3.4%), and 148 (45.7%) patients, respectively. Twenty-nine (9.0%) patients were treated with more than one antiviral agent. Forty-eight (14.8%) patients were treated with tocilizumab and 53 (16.4%) patients received baricitinib therapy. The acute kidney injury (AKI) occurred in 81 (25.0%) patients and 39 (12.0%) patients were admitted to intensive care units. Fungal infections were observed in 55 (17.0%) patients. Fifty (15.4%) patients lost their graft. The 28-d mortality rate of patients was 9.0% and 42 (13.0%) patients died by the end of follow-up. Multivariate Cox regression analysis identified that cerebrovascular disease, AKI incidence, interleukin (IL)-6 level of >6.8 pg/mL, daily dose of corticosteroids of >50 mg, and fungal infection were all associated with an increased risk of death for hospitalized patients. Conclusions: Our findings demonstrate that hospitalized KTRs with COVID-19 are at high risk of mortality. The administration of immunomodulators or the late application of antiviral drugs does not improve patient survival, while higher doses of corticosteroids may increase the death risk.
Author contributions Research idea and study design: Duo LV, Jianyong WU, and Jianghua CHEN; Data acquisition: Duo LV, Xishao XIE, Qinyun YANG, Zhimin CHEN, Guangjun LIU, Rending WANG, Wenhan PENG, and Hongfeng HUANG; Data analysis/ interpretation and statistical analysis: Duo LV and Xishao XIE; Supervision or mentorship: Jianyong WU and Jianghua CHEN. All the authors have read and approved the final manuscript, and therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.
Compliance with ethics guidelines Duo LV, Xishao XIE, Qinyun YANG, Zhimin CHEN, Guangjun LIU, Wenhan PENG, Rending WANG, Hongfeng HUANG, Jianghua CHEN, and Jianyong WU declare that they have no conflicts of interest. This study was approved by the Clinical Research Ethics Committee of the First Affiliated Hospital of Zhejiang University (expedition review No. 63 in 2023) . The Ethics Committee authorized the informed consent waiver. This study was performed in accordance with the Declaration of Helsinki.
Supplementary information Table S1
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Late treatment
is less effective
is less effective
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