Effectiveness of remdesivir in patients with COVID-19 and severe renal insufficiency: a nationwide cohort study in Japan.

Gen Yamada, Yusuke Ogawa, Noriko Iwamoto, Michiyo Suzuki, Yoshie Yamada, Takahiro Itaya, Kayoko Hayakawa, Norio Ohmagari, Yosuke Yamamoto
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Abstract

Background: The effectiveness of remdesivir in patients with coronavirus disease 2019 (COVID-19) and severe renal insufficiency remains underexplored.

Objectives: To evaluate whether remdesivir reduces the risk of mortality or invasive mechanical ventilation/extracorporeal membrane oxygenation (IMV/ECMO) in this population.

Methods: This retrospective observational study utilising the COVID-19 Registry Japan (COVIREGI-JP) included noncritical patients with COVID-19 and severe renal insufficiency (defined as serum creatinine levels ≥3 mg/dL, on maintenance dialysis, or kidney transplant recipients) admitted to Japanese hospitals within 7 days of symptom onset between January 1, 2020 and May 8, 2023. Patients were classified into the remdesivir group if remdesivir was initiated within the first 2 days of admission. We estimated the multivariable-adjusted hazard ratio (HR) for mortality and initiation of IMV/ECMO using landmark analysis to address immortal time bias.

Results: Among the 1,449 patients included in the landmark analysis (median age, 74 years [interquartile range 62-84 years]; 992 [68.5%] were male), 272 initiated remdesivir within the first 2 days of admission. During the 28 days from the landmark timepoint, 19 (7.0%) and 136 (11.6%) patients in the remdesivir and control groups, respectively, had an outcome. The remdesivir group had a lower risk of mortality or IMV/ECMO initiation than the control group (adjusted HR, 0.44; 95% confidence interval, 0.23-0.83).

Conclusions: In noncritical patients with COVID-19 and severe renal insufficiency at admission, initiating remdesivir early after disease onset, within the first 2 days of admission, led to a lower risk of mortality or IMV/ECMO initiation, compared with non-initiation of remdesivir.

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雷米替韦对 COVID-19 和严重肾功能不全患者的疗效:日本全国范围的队列研究。
背景:雷米替韦对冠状病毒病2019(COVID-19)和严重肾功能不全患者的疗效仍未得到充分探讨:目的:评估雷米替韦是否能降低该人群的死亡率或侵入性机械通气/体外膜肺氧合(IMV/ECMO)风险:这项回顾性观察研究利用了日本COVID-19登记处(COVIREGI-JP),纳入了2020年1月1日至2023年5月8日期间日本医院收治的发病7天内患有COVID-19和严重肾功能不全(定义为血清肌酐水平≥3 mg/dL、接受维持性透析或肾移植受者)的非危重患者。如果患者在入院后 2 天内开始使用雷米地韦则被归入雷米地韦组。我们采用地标分析法估算了死亡率和开始使用 IMV/ECMO 的多变量调整后危险比 (HR),以消除不死时间偏差:在纳入地标分析的 1,449 名患者中(中位年龄 74 岁[四分位间范围 62-84 岁];992 名[68.5%]为男性),有 272 名患者在入院后 2 天内开始使用雷米替韦。从标志性时间点算起的 28 天内,雷米替韦组和对照组分别有 19 名(7.0%)和 136 名(11.6%)患者出现了治疗结果。与对照组相比,雷米替韦组的死亡或启动IMV/ECMO的风险较低(调整后HR,0.44;95%置信区间,0.23-0.83):结论:对于入院时患有COVID-19和严重肾功能不全的非危重患者,与不使用雷米替韦相比,在发病后2天内尽早使用雷米替韦可降低死亡或启动IMV/ECMO的风险。
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