Skip to main navigation menu Skip to main content Skip to site footer

Original article

Vol. 153 No. 8 (2023)

Treatment effect of remdesivir on the mortality of hospitalised COVID-19 patients in Switzerland across different patient groups: a tree-based model analysis

  • Janne Estill
  • Plamenna Venkova-Marchevska
  • Huldrych F. Günthard
  • Sara Botero-Mesa
  • Amaury Thiabaud
  • Maroussia Roelens
  • Laure Vancauwenberghe
  • Lauro Damonti
  • Ulrich Heininger
  • Anne Iten
  • Peter W. Schreiber
  • Rami Sommerstein
  • Sarah Tschudin-Sutter
  • Nicolas Troillet
  • Danielle Vuichard-Gysin
  • Andreas Widmer
  • Torsten Hothorn
  • Olivia Keiser
Cite this as:
Swiss Med Wkly. 2023;153:40095


AIMS OF THE STUDY: Remdesivir has shown benefits against COVID-19. However, it remains unclear whether, to what extent, and among whom remdesivir can reduce COVID-19-related mortality. We explored whether the treatment response to remdesivir differed by patient characteristics.

METHODS: We analysed data collected from a hospital surveillance study conducted in 21 referral hospitals in Switzerland between 2020 and 2022. We applied model-based recursive partitioning to group patients by the association between treatment levels and mortality. We included either treatment (levels: none, remdesivir within 7 days of symptom onset, remdesivir after 7 days, or another treatment), age and sex, or treatment only as regression variables. Candidate partitioning variables included a range of risk factors and comorbidities (and age and sex unless included in regression). We repeated the analyses using local centring to correct the results for the propensity to receive treatment.

RESULTS: Overall (n = 21,790 patients), remdesivir within 7 days was associated with increased mortality (adjusted hazard ratios 1.28–1.54 versus no treatment). The CURB-65 score caused the most instability in the regression parameters of the model. When adjusted for age and sex, patients receiving remdesivir within 7 days of onset had higher mortality than those not treated in all identified eight patient groups. When age and sex were included as partitioning variables instead, the number of groups increased to 19–20; in five to six of those branches, mortality was lower among patients who received early remdesivir. Factors determining the groups where remdesivir was potentially beneficial included the presence of oncological comorbidities, male sex, and high age.

CONCLUSIONS: Some subgroups of patients, such as individuals with oncological comorbidities or elderly males, may benefit from remdesivir.


  1. Cihlar T, Mackman RL. Journey of remdesivir from the inhibition of hepatitis C virus to the treatment of COVID-19. Antivir Ther. 2022 Apr;27(2):13596535221082773. 10.1177/13596535221082773 DOI:
  2. Warren TK, Jordan R, Lo MK, Ray AS, Mackman RL, Soloveva V, et al. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature. 2016 Mar;531(7594):381–5. 10.1038/nature17180 DOI:
  3. Sheahan TP, Sims AC, Graham RL, Menachery VD, Gralinski LE, Case JB, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med. 2017 Jun;9(396):eaal3653. 10.1126/scitranslmed.aal3653 DOI:
  4. Saint-Raymond A, Sato J, Kishioka Y, Teixeira T, Hasslboeck C, Kweder SL. Remdesivir emergency approvals: a comparison of the U.S., Japanese, and EU systems. Expert Rev Clin Pharmacol. 2020 Oct;13(10):1095–101. 10.1080/17512433.2020.1821650 DOI:
  5. U.S. Food & Drug Administration. FDA news release: FDA Approves First Treatment for COVID-19. October 22, 2020. Available from: DOI:
  6. Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al.; ACTT-1 Study Group Members. Remdesivir for the Treatment of Covid-19 - Final Report. N Engl J Med. 2020 Nov;383(19):1813–26. 10.1056/NEJMoa2007764 DOI:
  7. Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020 May;395(10236):1569–78. 10.1016/S0140-6736(20)31022-9
  8. Moynihan R, Macdonald H, Bero L, Godlee F. Commercial influence and COVID-19. BMJ 2020 Jun 24;369:m2456. 10.1136/bmj.m2456 DOI:
  9. WHO Solidarity Trial Consortium. Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO Solidarity randomised trial and updated meta-analyses. Lancet. 2022 May;399(10339):1941–53. 10.1016/S0140-6736(22)00519-0 DOI:
  10. World Health Organization. WHO recommends against the use of remdesivir in COVID-19 patients. 20 November 2020, Geneva, Switzerland: World Health Organization. Available from:
  11. World Health Organization. Therapeutics and COVID-19: living guideline. 14 July 2022, Geneva, Switzerland: World Health Organization. Available from:
  12. Thiabaud A, Iten A, Balmelli C, Senn L, Troillet N, Widmer A, et al. Cohort profile: SARS-CoV-2/COVID-19 hospitalised patients in Switzerland. Swiss Med Wkly. 2021 Feb;151(708):w20475. 10.4414/smw.2021.20475 DOI:
  13. Gil-Sierra MD, Briceño-Casado MP, Alegre-Del Rey EJ, Sánchez-Hidalgo M. Efficacy of early use of remdesivir: a systematic review of subgroup analysis. Rev Esp Quimioter. 2022 Jun;35(3):249–59. 10.37201/req/154.2021 DOI:
  14. Seibold H, Zeileis A, Hothorn T. Model-Based Recursive Partitioning for Subgroup Analyses. Int J Biostat. 2016 May;12(1):45–63. 10.1515/ijb-2015-0032 DOI:
  15. Seibold H, Zeileis A, Hothorn T. Individual treatment effect prediction for amyotrophic lateral sclerosis patients. Stat Methods Med Res. 2018 Oct;27(10):3104–25. 10.1177/0962280217693034 DOI:
  16. Hothorn T, Hornik K, Zeileis A. Ctree: Conditional Inference Trees. Available from:
  17. Hothorn T, Hornik K, Zeileis A. Unbiased Recursive Partitioning: A Conditional Inference Framework. J Comput Graph Stat. 2006;15(3):651–74. 10.1198/106186006X133933 DOI:
  18. Athey S, Tibshirani J, Wager S. Generalized random forests. Ann Stat. 2019;47(2):1148–78. 10.1214/18-AOS1709 DOI:
  19. Robinson PM. Root-N-consistent semiparameteric regression. Econometrica. 1988;56(4):931–54. 10.2307/1912705 DOI:
  20. Gao Z, Hastie T. Estimating Heterogeneous Treatment Effects for General Responses [preprint]. 2022; arXiv:2103.04277.v4.
  21. Hothorn T, Seibold H, Zeileis A. partykit: A Toolkit for Recursive Partytioning. Version 1.2-15. 2021; Available from:
  22. Mahamat-Saleh Y, Fiolet T, Rebeaud ME, Mulot M, Guihur A, El Fatouhi D, et al. Diabetes, hypertension, body mass index, smoking and COVID-19-related mortality: a systematic review and meta-analysis of observational studies. BMJ Open. 2021 Oct;11(10):e052777. 10.1136/bmjopen-2021-052777 DOI:
  23. Izcovich A, Ragusa MA, Tortosa F, Lavena Marzio MA, Agnoletti C, Bengolea A, et al. Prognostic factors for severity and mortality in patients infected with COVID-19: A systematic review. PLoS One. 2020 Nov;15(11):e0241955. 10.1371/journal.pone.0241955 DOI:
  24. Mahendra M, Nuchin A, Kumar R, Shreedhar S, Mahesh PA. Predictors of mortality in patients with severe COVID-19 pneumonia - a retrospective study. Adv Respir Med. 2021;89(2):135–44. 10.5603/ARM.a2021.0036 DOI:
  25. Jdiaa SS, Mansour R, El Alayli A, Gautam A, Thomas P, Mustafa RA. COVID-19 and chronic kidney disease: an updated overview of reviews. J Nephrol. 2022 Jan;35(1):69–85. 10.1007/s40620-021-01206-8 DOI:
  26. Lim WS, van der Eerden MM, Laing R, Boersma WG, Karalus N, Town GI, et al. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax. 2003 May;58(5):377–82. 10.1136/thorax.58.5.377 DOI:
  27. Satici C, Demirkol MA, Sargin Altunok E, Gursoy B, Alkan M, Kamat S, et al. Performance of pneumonia severity index and CURB-65 in predicting 30-day mortality in patients with COVID-19. Int J Infect Dis. 2020 Sep;98:84–9. 10.1016/j.ijid.2020.06.038 DOI:
  28. Han HJ, Nwagwu C, Anyim O, Ekweremadu C, Kim S. COVID-19 and cancer: from basic mechanisms to vaccine development using nanotechnology. Int Immunopharmacol. 2021 Jan;90:107247. 10.1016/j.intimp.2020.107247 DOI:
  29. Yeoh CB, Lee KJ, Rieth EF, Mapes R, Tchoudovskaia AV, Fischer GW, et al. COVID-19 in the Cancer Patient. Anesth Analg. 2020 Jul;131(1):16–23. 10.1213/ANE.0000000000004884 DOI:
  30. Belsky JA, Tullius BP, Lamb MG, Sayegh R, Stanek JR, Auletta JJ. COVID-19 in immunocompromised patients: A systematic review of cancer, hematopoietic cell and solid organ transplant patients. J Infect. 2021 Mar;82(3):329–38. 10.1016/j.jinf.2021.01.022 DOI:
  31. Kaka AS, MacDonald R, Linskens EJ, Langsetmo L, Vela K, Duan-Porter W, et al. Major Update 2: Remdesivir for Adults With COVID-19: A Living Systematic Review and Meta-analysis for the American College of Physicians Practice Points. Ann Intern Med. 2022 May;175(5):701–9. 10.7326/M21-4784 DOI:
  32. Humeniuk R, Mathias A, Cao H, Osinusi A, Shen G, Chng E, et al. Safety, Tolerability, and Pharmacokinetics of Remdesivir, An Antiviral for Treatment of COVID-19, in Healthy Subjects. Clin Transl Sci. 2020 Sep;13(5):896–906. 10.1111/cts.12840 DOI:
  33. Marrone A, Nevola R, Sellito A, et al. Remdesivir plus dexamethasone versus dexamethasone alone for the treatment of COVID-19 patients requiring supplemental O2 therapy: a prospective controlled non-randomized study. Clin Infect Dis. 2022 Aug 24;75(1):e403-9. DOI:
  34. Hussain Alsayed HA, Saheb Sharif-Askari F, Saheb Sharif-Askari N, Hussain AA, Hamid Q, Halwani R. Early administration of remdesivir to COVID-19 patients associates with higher recovery rate and lower need for ICU admission: A retrospective cohort study. PLoS One. 2021 Oct;16(10):e0258643. 10.1371/journal.pone.0258643 DOI:
  35. Falcone M, Suardi LR, Tiseo G, Barbieri C, Giusti L, Galfo V, et al. Early Use of Remdesivir and Risk of Disease Progression in Hospitalized Patients With Mild to Moderate COVID-19. Clin Ther. 2022 Mar;44(3):364–73. 10.1016/j.clinthera.2022.01.007 DOI:
  36. Wong CK, Lau KT, Au IC, et al. Optimal Timing of Remdesivir Initiation in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) Administered With Dexamethasone. Clin Infect Dis. 2022 Aug 24;75(1):e499-508. DOI:
  37. ACTIV-3-Therapeutics for Inpatients with COVID-19 (TICO) Study Group. Tixagevimab-cilgavimab for treatment of patients hospitalised with COVID-19: a randomized, double-blind, phase 3 trial. Lancet Respir Med. 2022 Oct;10(10):972-84. DOI:
  38. König IR, Fuchs O, Hansen G, von Mutius E, Kopp MV. What is precision medicine? Eur Respir J. 2017 Oct;50(4):1700391. 10.1183/13993003.00391-2017 DOI:

Most read articles by the same author(s)

1 2 3 4 > >>