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

The effectiveness of remdesivir in patients with coronavirus disease 2019 (COVID-19) and severe renal insufficiency remains underexplored. To evaluate whether remdesivir reduces the risk of mortality or invasive mechanical ventilation/extracorporeal membrane oxygenation (IMV/ECMO) in this population. 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. 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). 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.

针对新型冠状病毒肺炎（COVID-19）合并重度肾功能不全患者，瑞德西韦（remdesivir）的治疗有效性仍有待深入探索。本研究旨在评估该类人群中，瑞德西韦是否可降低患者死亡或有创机械通气/体外膜肺氧合（invasive mechanical ventilation/extracorporeal membrane oxygenation, IMV/ECMO）的发生风险。本研究为回顾性观察性研究，依托日本COVID-19登记数据库（COVID-19 Registry Japan, COVIREGI-JP）开展，纳入了2020年1月1日至2023年5月8日期间，在症状出现7天内于日本医疗机构住院的非重症COVID-19合并重度肾功能不全患者。重度肾功能不全定义为血清肌酐≥3mg/dL、接受维持性透析或肾移植受者。若患者在入院后2天内启动瑞德西韦治疗，则将其归入瑞德西韦组。为规避不朽时间偏倚（immortal time bias），本研究采用地标分析（landmark analysis）方法，估算了患者死亡或启动IMV/ECMO的多变量校正风险比（hazard ratio, HR）。本研究地标分析共纳入1449例患者，其中位年龄为74岁（四分位间距62~84岁），男性992例（占比68.5%）；272例患者在入院后2天内启动了瑞德西韦治疗。自地标时间节点起的28天随访期内，瑞德西韦组与对照组分别有19例（7.0%）、136例（11.6%）患者发生了主要结局事件。与对照组相比，瑞德西韦组患者的死亡或启动IMV/ECMO风险更低（校正后HR=0.44；95%置信区间：0.23~0.83）。对于入院时为非重症、合并重度肾功能不全的COVID-19患者，相较于未启动瑞德西韦治疗者，在入院后2天内早期启动瑞德西韦治疗可降低其死亡或启动IMV/ECMO的风险。