A Systematic Review and Meta-analysis of the Effectiveness of Remdesivir to Treat SARS-CoV-2 in Hospitalized Patients: Have the Guidelines Evolved With the Evidence?
Michele Bartoletti, Essy Mozaffari, Alpesh Amin, Yohei Doi, Paul Loubet, Christina G. Rivera, Michael Roshon, Aaditya Rawal, Emily Kaiser, M Nicolae, Shuai Fu, Tom Oppelt, Mel Chiang, Paul E. Sax, André C. Kalil
Abstract
BACKGROUND: With progressive accumulation of knowledge on SARS-CoV-2 infection clinical management, treatment guidelines recommended several options including remdesivir, a broad-spectrum antiviral. Given the evolving nature of coronavirus disease 2019, capturing the totality of scientific evidence from clinical trials and observational studies is critical to inform clinical decision making. We conducted a systematic literature review with meta-analysis to summarize the effectiveness of remdesivir among hospitalized adults. METHODS: We systematically searched MEDLINE, Embase and Cochrane Library databases for interventional and observational studies examining remdesivir efficacy. A rigorous double-reviewer approach was used for source identification, screening, data extraction and risk of bias assessment. A hierarchical random-effects model meta-analysis was used, with subgroup analyses for randomized controlled trials (RCTs) and real-world (RW) studies. RESULTS: From January 2019 to December 2023 >18 000 sources were screened, and 122 unique studies were identified, reporting on 25 174 participants in RCTs and 1 279 859 in RW studies. Remdesivir significantly increased survival in the overall population (odds ratio, 0.69 [95% confidence interval, .55-.86]; P = .001] across SARS-CoV-2 variants and disease severity levels: no supplemental oxygen (0.81 [.75-.88]), low-flow oxygen (0.71 [.64-.79]), high-flow oxygen (0.87 [.83-.91]), and invasive mechanical ventilation (0.78 [.68-.90]). Rehospitalization risk was significantly reduced in patients receiving remdesivir (odds ratio, 0.72 [95% confidence interval, .64-.81]). CONCLUSIONS: Our comprehensive systematic literature review, capturing the totality of evidence, showed a significant survival benefit among patients hospitalized for SARS-CoV-2 infection and receiving remdesivir, across all disease severity levels. To assure that healthcare providers are aware of and deploy evidence-based optimal care, recommendations should rely on both RCT and RW data.