The efficacy of remdesivir in coronavirus disease 2019 (COVID-19): a systematic review

  • Amirhossein Roshanshad Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran AND Department of MPH, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
  • Alireza Kamalipour Department of MPH, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran AND Department of Ophthalmology, Hamilton Glaucoma Center, Shiley Eye Institute, University of California, San Diego, California, United States
  • Mohammad Ali Ashraf Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
  • Romina Roshanshad Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
  • Sirous Jafari Department of Infectious Diseases, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
  • Pershang Nazemi Department of Infectious Diseases, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  • Mohammadreza Akbari Mail Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran AND Department of MPH, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Keywords:
Coronavirus disease 2019 (COVID-19);, SARS-CoV-2;, Remdesivir;, Efficacy

Abstract

Background and Objectives: Researchers all around the world are working hard to find an effective treatment for the new coronavirus 2019. We performed a comprehensive systematic review to investigate the latest clinical evidence on the efficacy and safety of treatment with Remdesivir in hospitalized patients with COVID-19.
Materials and Methods: We performed a systematic search in Pubmed, Embase, Web of Science, Google scholar and MedRxiv for relevant observational and interventional studies. The outcomes measures were mortality rates, improvement rates, time to clinical improvement, all adverse event rates and severe adverse event rates.
Results: Three randomized controlled trials and 2 cohort studies were included in our study. In the 2 cohort studies, patients received Remdesivir for 10 days. 2 RCTs evaluated 10-day efficacy of treatment with Remdesivir versus placebo group and the other RCT compared its 5-day regimen versus 10-day regimen. Visual inspection of the forest plots revealed that the efficacy of Remdesivir was not much different in reducing 28-day mortality versus 14-day mortality rates. Besides, 10-day treatment regimen overpowered 5-day treatment and placebo in decreasing time to clinical improvement. All adverse event rates did not have a significant difference; however, severe adverse event rate was lower in the 5-day Remdesivir group compared to the 10-day and placebo groups.
Conclusion: 5-day course of Remdesivir therapy in COVID-19 patients is probably efficacious and safe, and patients without invasive mechanical ventilation benefit the most. Treatment can be extended to 10 days if satisfactory improvement is not seen by day 5. Most benefits from Remdesivir therapy take place in the first 14 days of the start of the treatment.

References

1. Coronavirus disease (COVID-19) Weekly Epidemiological Update WHO; 2020 [updated September 27, 2020]. Available from: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200928-weekly-epi-update.pdf?sfvrsn=9e354665_6.
2. Nicola M, Alsafi Z, Sohrabi C, Kerwan A, Al-Jabir A, Iosifidis C, et al. The socio-economic implications of the coronavirus pandemic (COVID-19): A review. Int J Surg 2020; 78: 185-193.
3. Tang D, Comish P, Kang R. The hallmarks of COVID-19 disease. PLoS Pathog 2020; 16(5): e1008536.
4. Baden L, Rubin E. Covid-19 — The Search for Effective Therapy. N Engl J Med 2020; 382: 1851-1852.
5. Siegel D, Hui H, Doerffler E, Clarke M, Chun K, Zhang L, et al. Discovery and synthesis of a phosphoramidate prodrug of a pyrrolo[2,1-f][triazin-4-amino] adenine C-nucleoside (GS-5734) for the treatment of Ebola and Emerging viruses. J Med Chem 2017; 60: 1648-1661.
6. 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; 9:eaal3653.
7. Williamson BN, Feldmann F, Schwarz B, Meade-White K, Porter DP, Schulz J, et al. Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Nature 2020; 585: 273-276.
8. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020; 30: 269-271.
9. Norrie J. Remdesivir for COVID-19: challenges of underpowered studies. Lancet 2020; 395: 1525-1527.
10. U.S. Food and Drug Administration. Coronavirus (COVID-19) Update: FDA Issues Emergency Use Authorization for Potential COVID-19 Treatment [Internet]. 2020 [cited 20 June, 2020]. Available from: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-issues-emergency-use-authorization-potential-covid-19-treatment
11. Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 2015; 4: 1.
12. Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011; 343:d5928.
13. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010; 25: 603-605.
14. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 2005; 5: 13.
15. Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A, et al. Compassionate use of Remdesivir for patients with severe Covid-19. N Engl J Med 2020; 382:2327-2336.
16. Antinori S, Cossu MV, Ridolfo AL, Rech R, Bonazzetti C, Pagani G, et al. Compassionate remdesivir treatment of severe Covid-19 pneumonia in intensive care unit (ICU) and Non-ICU patients: Clinical outcome and differences in post-treatment hospitalisation status. Pharmacol Res 2020; 158:104899.
17. Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the treatment of Covid-19 - preliminary report. N Engl J Med 2020; NEJMoa2007764.
18. Goldman JD, Lye DCB, Hui DS, Marks KM, Bruno R, Montejano R, et al. Remdesivir for 5 or 10 Days in Patients with Severe Covid-19. N Engl J Med 2020;NEJMoa2015301.
19. 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; 395:1569-1578.
20. Flanagan C. Gilead’s Virus Drug Seen in Short Supply for Americans [Internet]. 2020. [cited 20 June, 2020]. Available from: https://www.bloomberg.com/news/articles/2020-05-11/gilead-s-covid-19-drug-seen-in-short-supply-for-americans
21. Wu J, Wu B, Lai T. Compassionate use of Remdesivir in Covid-19. N Engl J Med 2020; 382:e101.
Published
2020-10-31
How to Cite
1.
Roshanshad A, Kamalipour A, Ashraf MA, Roshanshad R, Jafari S, Nazemi P, Akbari M. The efficacy of remdesivir in coronavirus disease 2019 (COVID-19): a systematic review. Iran J Microbiol. 12(5):376-387.
Section
Review Article(s)