Effects of Remdesivir in Patients Hospitalised with COVID-19: a Systematic Review and Individual Patient Data Meta-analysis of Randomised Controlled Trials

Background: Interpretation of the evidence from randomised controlled trials (RCTs) of remdesivir in patients treated in hospital for COVID-19 is conflicting. We aimed to assess the benefits and harms of remdesivir compared with placebo or usual care in these patients, and whether treatment effects differed between prespecified patient subgroups.

Methods: For this systematic review and meta-analysis, we searched PubMed, Embase, the Cochrane COVID-19 trial registry, ClinicalTrials.gov, the International Clinical Trials Registry Platform, and preprint servers from Jan 1, 2020, until April 11, 2022, for RCTs of remdesivir in adult patients hospitalised with COVID-19, and contacted the authors of eligible trials to request individual patient data. The primary outcome was all-cause mortality at day 28 after randomisation. We used multivariable hierarchical regression-adjusting for respiratory support, age, and enrollment period-to investigate effect modifiers. This study was registered with PROSPERO, CRD42021257134.

Findings: Our search identified 857 records, yielding nine RCTs eligible for inclusion. Of these nine eligible RCTs, individual data were provided for eight, covering 10 480 patients hospitalised with COVID-19 (99% of such patients included in such RCTs worldwide) recruited between Feb 6, 2020, and April 1, 2021. Within 28 days of randomisation, 662 (12·5%) of 5317 patients assigned to remdesivir and 706 (14·1%) of 5005 patients assigned to no remdesivir died (adjusted odds ratio [aOR] 0·88, 95% CI 0·78-1·00, p=0·045). We found evidence for a credible subgroup effect according to respiratory support at baseline (p=0·019). Of patients who were ventilated-including those who received high-flow oxygen-253 (30·0%) of 844 patients assigned to remdesivir died compared with 241 (28·5%) of 846 patients assigned to no remdesivir (aOR 1·10 [0·88-1·38]; low-certainty evidence). Of patients who received no oxygen or low-flow oxygen, 409 (9·1%) of 4473 patients assigned to remdesivir died compared with 465 (11·2%) of 4159 patients assigned to no remdesivir (0·80 [0·70-0·93]; high-certainty evidence). No credible subgroup effect was found for time to start of remdesivir after symptom onset, age, presence of comorbidities, enrolment period, or corticosteroid use. Remdesivir did not increase the frequency of severe or serious adverse events.

Interpretation: This individual patient data meta-analysis showed that remdesivir reduced mortality in patients hospitalised with COVID-19 who required no or conventional oxygen support, but was underpowered to evaluate patients who were ventilated when receiving remdesivir. The effect size of remdesivir in patients with more respiratory support or acquired immunity and the cost-effectiveness of remdesivir remain to be further elucidated.

Funding: EU-RESPONSE.

Citing Articles

Effect of Early and Delayed Treatment With Remdesivir on Mortality in Patients Hospitalized With COVID-19.

Makkar S, Hansen K, Hotaling N, Toler A, Sidky H Open Forum Infect Dis. 2025; 12(2):ofae740.

PMID: 40041442 PMC: 11878583. DOI: 10.1093/ofid/ofae740.

Characteristics associated with high hospital spending over 1 year among patients hospitalised for COVID-19 in the USA: a cohort study.

Nair-Desai S, Chambers L, Soto M, Behr C, Lovgren L, Zandstra T BMJ Public Health. 2025; 1(1):e000263.

PMID: 40017864 PMC: 11812720. DOI: 10.1136/bmjph-2023-000263.

Thiol-Reactive or Redox-Active: Revising a Repurposing Screen Led to a New Invalidation Pipeline and Identified a True Noncovalent Inhibitor Against Papain-like Protease from SARS-CoV-2.

Kuzikov M, Morasso S, Reinshagen J, Wolf M, Monaco V, Cozzolino F ACS Pharmacol Transl Sci. 2025; 8(1):66-77.

PMID: 39816795 PMC: 11729419. DOI: 10.1021/acsptsci.4c00325.

Real-world evidence of remdesivir in formerly hospitalized COVID-19 patients: patient-reported and functional outcomes.

Fesu D, Barczi E, Csoma B, Polivka L, Boga M, Horvath G BMC Infect Dis. 2025; 25(1):43.

PMID: 39789448 PMC: 11715443. DOI: 10.1186/s12879-024-10398-w.

Cardiac Damage in Patients Infected with Different SARS-CoV-2 Variants of Concern.

Burkert F, Oberhollenzer M, Kresse D, Niederreiter S, Filippi V, Lanser L Microorganisms. 2025; 12(12.

PMID: 39770819 PMC: 11676750. DOI: 10.3390/microorganisms12122617.

References

Janiaud P, Axfors C, Vant Hooft J, Saccilotto R, Agarwal A, Appenzeller-Herzog C . The worldwide clinical trial research response to the COVID-19 pandemic - the first 100 days. F1000Res. 2020; 9:1193. PMC: 7539080. DOI: 10.12688/f1000research.26707.2. View

White I, Royston P, Wood A . Multiple imputation using chained equations: Issues and guidance for practice. Stat Med. 2011; 30(4):377-99. DOI: 10.1002/sim.4067. View

Nevalainen O, Horstia S, Laakkonen S, Rutanen J, Mustonen J, Kalliala I . Effect of remdesivir post hospitalization for COVID-19 infection from the randomized SOLIDARITY Finland trial. Nat Commun. 2022; 13(1):6152. PMC: 9579198. DOI: 10.1038/s41467-022-33825-5. View

Brown A, Won J, Graham R, Dinnon 3rd K, Sims A, Feng J . Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase. Antiviral Res. 2019; 169:104541. PMC: 6699884. DOI: 10.1016/j.antiviral.2019.104541. View

Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y . Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020; 395(10236):1569-1578. PMC: 7190303. DOI: 10.1016/S0140-6736(20)31022-9. View

Dodd L, Follmann D, Wang J, Koenig F, Korn L, Schoergenhofer C . Endpoints for randomized controlled clinical trials for COVID-19 treatments. Clin Trials. 2020; 17(5):472-482. PMC: 7611901. DOI: 10.1177/1740774520939938. View

Osuchowski M, Winkler M, Skirecki T, Cajander S, Shankar-Hari M, Lachmann G . The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity. Lancet Respir Med. 2021; 9(6):622-642. PMC: 8102044. DOI: 10.1016/S2213-2600(21)00218-6. View

Mahajan L, Singh A, Gifty . Clinical outcomes of using remdesivir in patients with moderate to severe COVID-19: A prospective randomised study. Indian J Anaesth. 2021; 65(Suppl 1):S41-S46. PMC: 7993042. DOI: 10.4103/ija.IJA_149_21. View

Lingas G, Neant N, Gaymard A, Belhadi D, Peytavin G, Hites M . Effect of remdesivir on viral dynamics in COVID-19 hospitalized patients: a modelling analysis of the randomized, controlled, open-label DisCoVeRy trial. J Antimicrob Chemother. 2022; 77(5):1404-1412. PMC: 9383489. DOI: 10.1093/jac/dkac048. View

10.

. A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis. 2020; 20(8):e192-e197. PMC: 7292605. DOI: 10.1016/S1473-3099(20)30483-7. View

11.

Stewart L, Clarke M, Rovers M, Riley R, Simmonds M, Stewart G . Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data: the PRISMA-IPD Statement. JAMA. 2015; 313(16):1657-65. DOI: 10.1001/jama.2015.3656. View

12.

Barratt-Due A, Olsen I, Nezvalova-Henriksen K, Kasine T, Lund-Johansen F, Hoel H . Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19 : A Randomized Trial. Ann Intern Med. 2021; 174(9):1261-1269. PMC: 8279143. DOI: 10.7326/M21-0653. View

13.

Takashita E, Yamayoshi S, Simon V, van Bakel H, Sordillo E, Pekosz A . Efficacy of Antibodies and Antiviral Drugs against Omicron BA.2.12.1, BA.4, and BA.5 Subvariants. N Engl J Med. 2022; 387(5):468-470. PMC: 9342381. DOI: 10.1056/NEJMc2207519. View

14.

Skoetz N, Goldkuhle M, van Dalen E, Akl E, Trivella M, Mustafa R . GRADE guidelines 27: how to calculate absolute effects for time-to-event outcomes in summary of findings tables and Evidence Profiles. J Clin Epidemiol. 2019; 118:124-131. DOI: 10.1016/j.jclinepi.2019.10.015. View

15.

Riley R, Legha A, Jackson D, Morris T, Ensor J, Snell K . One-stage individual participant data meta-analysis models for continuous and binary outcomes: Comparison of treatment coding options and estimation methods. Stat Med. 2020; 39(19):2536-2555. DOI: 10.1002/sim.8555. View

16.

Guyatt G, Oxman A, Kunz R, Vist G, Falck-Ytter Y, Schunemann H . What is "quality of evidence" and why is it important to clinicians?. BMJ. 2008; 336(7651):995-8. PMC: 2364804. DOI: 10.1136/bmj.39490.551019.BE. View

17.

Williamson B, Feldmann F, Schwarz B, Meade-White K, Porter D, Schulz J . Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Nature. 2020; 585(7824):273-276. PMC: 7486271. DOI: 10.1038/s41586-020-2423-5. View

18.

Horby P, Lim W, Emberson J, Mafham M, Bell J, Linsell L . Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2020; 384(8):693-704. PMC: 7383595. DOI: 10.1056/NEJMoa2021436. View

19.

Pan H, Peto R, Henao-Restrepo A, Preziosi M, Sathiyamoorthy V, Abdool Karim Q . Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results. N Engl J Med. 2020; 384(6):497-511. PMC: 7727327. DOI: 10.1056/NEJMoa2023184. View

20.

Jackson D, Law M, Rucker G, Schwarzer G . The Hartung-Knapp modification for random-effects meta-analysis: A useful refinement but are there any residual concerns?. Stat Med. 2017; 36(25):3923-3934. PMC: 5628734. DOI: 10.1002/sim.7411. View