Evaluation of the effectiveness of remdesivir in severe COVID-19 using observational data from a prospective national cohort study

Background Remdesivir has been evaluated in clinical trial populations, but there is a sparsity of evidence evaluating effectiveness in general populations. Methods Adults eligible to be treated with remdesivir, requiring oxygen but not ventilated, were identified from UK patients hospitalised with COVID-19. Patients treated with remdesivir within 24h of hospitalisation were compared with propensity-score matched controls; estimates of effectiveness were calculated for short-term outcomes (14-day mortality, 28-day mortality, time-to-recovery among others) using multivariable modelling. Results 9,278 out of 39,330 patients satisfied eligibility criteria. 1,549 patients were identified as ‘treated’ and matched with 4,964 controls. Patients were 62% male, mean (SD) age 63.1 (15.6) years, 80% ‘White’ ethnicity, and symptomatic for a median of 6 days prior to baseline. There was no statistically significant benefit of remdesivir at 14 days in terms of mortality or clinical status; there were signals of effectiveness in time-to-recovery after day 9, and a reduction in 28-day mortality. Conclusion In a real-world setting, initiation of remdesivir within 24h of hospitalisation in conjunction with standard of care was not associated with a benefit at 14 days but supports clinical trial evidence of a potential reduction in 28-day mortality. ### Competing Interest Statement All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: BNA, ARH, APJ and CGG report: the manufacturer of remdesivir, Gilead, is involved in funding trials that the Liverpool Clinical Trials unit is co-ordinating: a randomised controlled trial (HART-CT) that is fully funded by Gilead and sponsored by the University of Liverpool; and a trial (REALTO) that is part funded by Gilead. APJ is the lead statistician on the HART-CT trial. PJMO reports personal fees from consultancies and from the European Respiratory Society; grants from the Medical Research Council (MRC), MRC Global Challenge Research Fund, EU, NIHR BRC, MRC/GSK, Wellcome Trust, NIHR (Health Protection Research Unit [HPRU] in Respiratory Infection); and is an NIHR senior investigator outside of the submitted work; his role as President of the British Society for Immunology was unpaid but travel and accommodation at some meetings was provided by the Society. MGS reports grants from NIHR UK, MRC UK, and HPRU in Emerging and Zoonotic Infections, University of Liverpool during the conduct of the study. ### Clinical Protocols ### Funding Statement ISARIC4C is funded by two major awards from the Medical Research Council (MRC; grant MC\_PC\_19059), and The National Institute For Health Research (NIHR; award CO-CIN-01). PJMO is supported by a NIHR Senior Investigator Award [award 201385]. The Liverpool clinical trials unit did not receive any direct funding for this work. DK is funded by UK MRC Precision Medicine Training Grant (MR/N013166/1-LGH/MS/MED2525). The views expressed are those of the authors and not necessarily those of the NHIR, or MRC. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval for data collection was given by the South Central - Oxford C Research Ethics Committee in England (Ref: 13/SC/0149) and by the Scotland A Research Ethics Committee (Ref: 20/SS/0028). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes This work uses data provided by patients and collected by the NHS as part of their care and support #DataSavesLives. ISARIC4C welcomes applications for data and material access through our Independent Data and Material Access Committee (https://isaric4c.net).