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Anti-Infective Agents

Editor-in-Chief

ISSN (Print): 2211-3525
ISSN (Online): 2211-3533

Meta-Analysis

The Effectiveness and Safety of Remdesivir for the Treatment of Patients With COVID-19: A Systematic Review and Meta-Analysis

Author(s): Timotius Ivan Hariyanto, Felix Kwenandar, Karunia Valeriani Japar, Vika Damay and Andree Kurniawan*

Volume 19, Issue 3, 2021

Published on: 09 October, 2020

Page: [333 - 340] Pages: 8

DOI: 10.2174/2211352518999201009124433

Price: $65

Abstract

Background: Coronavirus disease 2019 (COVID-19) is a pandemic disease that has significant implications on the global health burden. Currently, there is no widely accepted pharmacologic treatment for COVID-19. Remdesivir has been shown effective against various types of viruses, including coronaviruses. This study aimed at synthesizing the latest evidence regarding the effectiveness and safety of remdesivir as a potential treatment candidate against COVID-19.

Methods: This systematic review has been registered in PROSPERO (CRD42020183707). A systematic search of the literature was conducted in PubMed, PubMed Central, and Google Scholar through June 5th, 2020. Statistical analysis was done by using the Review Manager 5.4 tool. The risk of bias was evaluated using the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) and GRADE analysis was performed to determine the certainty of the evidence.

Results: Two studies with a total of 1,300 patients were included. Meta-analysis showed that remdesivir was associated with faster time to clinical improvement (MD -4.75 days; 95% CI -4.84 days to -4.65 days; p < 0.00001), reduction in mortality rate (RR 0.39; 95% CI 0.27 – 0.56; p < 0.00001) and fewer incidence of serious adverse events (RR 0.77; 95% CI 0.63 – 0.94; p = 0.01). GRADE analysis showed a high certainty for serious adverse events and moderate certainty for time to clinical improvement and mortality rate.

Conclusion: Remdesivir is more effective and safer compared with standard care of treatment for the treatment of COVID-19 because it was associated with faster time to clinical improvement, reduction in mortality rate, and fewer incidence of serious adverse events.

Keywords: COVID-19, SARS-CoV-2, coronavirus, remdesivir, PROSPERO, GRADE.

Graphical Abstract

[1]
Helmy, Y.A.; Fawzy, M.; Elaswad, A.; Sobieh, A.; Kenney, S.P.; Shehata, A.A. The COVID-19 pandemic: a comprehensive review of taxonomy, genetics, epidemiology, diagnosis, treatment, and control. J. Clin. Med., 2020, 9(4), E1225.
[http://dx.doi.org/10.3390/jcm9041225] [PMID: 32344679]
[2]
Who Health Organization. Coronavirus disease 2019 (COVID-19) Situation Report –138, 2020. Available from: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200606-covid-19-sitrep-138.pdf?sfvrsn=c8abfb17_44
[3]
Zhu, N.; Zhang, D.; Wang, W.; Li, X.; Yang, B.; Song, J.; Zhao, X.; Huang, B.; Shi, W.; Lu, R.; Niu, P.; Zhan, F.; Ma, X.; Wang, D.; Xu, W.; Wu, G.; Gao, G.F.; Tan, W. A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med., 2020, 382(8), 727-733.
[http://dx.doi.org/10.1056/NEJMoa2001017] [PMID: 31978945]
[4]
Rodriguez-Morales, A.J.; Cardona-Ospina, J.A.; Gutiérrez-Ocampo, E.; Villamizar-Peña, R.; Holguin-Rivera, Y.; Escalera-Antezana, J.P.; Alvarado-Arnez, L.E.; Bonilla-Aldana, D.K.; Franco-Paredes, C.; Henao-Martinez, A.F.; Paniz-Mondolfi, A.; Lagos-Grisales, G.J.; Ramírez-Vallejo, E.; Suárez, J.A.; Zambrano, L.I.; Villamil-Gómez, W.E.; Balbin-Ramon, G.J.; Rabaan, A.A.; Harapan, H.; Dhama, K.; Nishiura, H.; Kataoka, H.; Ahmad, T.; Sah, R. Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis. Travel Med. Infect. Dis., 2020, 34, 101623.
[http://dx.doi.org/10.1016/j.tmaid.2020.101623] [PMID: 32179124]
[5]
Kwenandar, F.; Japar, K.V.; Damay, V.; Hariyanto, T.I.; Tanaka, M.; Lugito, N.P.H.; Kurniawan, A. Coronavirus disease 2019 and cardiovascular system: A narrative review. Int. J. Cardiol. Heart Vasc., 2020, 29, 100557.
[http://dx.doi.org/10.1016/j.ijcha.2020.100557] [PMID: 32550259]
[6]
Liu, J.; Liu, Y.; Xiang, P.; Pu, L.; Xiong, H.; Li, C.; Zhang, M.; Tan, J.; Xu, Y.; Song, R.; Song, M.; Wang, L.; Zhang, W.; Han, B.; Yang, L.; Wang, X.; Zhou, G.; Zhang, T.; Li, B.; Wang, Y.; Chen, Z.; Wang, X. Neutrophil-to-lymphocyte ratio predicts severe illness patients with 2019 novel coronavirus in the early stage. J. Transl. Med., 2020, 18, 206.
[http://dx.doi.org/10.1186/s12967-020-02374-0] [PMID: 32434518]
[7]
Hariyanto, T.I.; Kurniawan, A. Dyslipidemia is associated with severe coronavirus disease 2019 (COVID-19) infection. Diabetes Metab. Syndr., 2020, 14(5), 1463-1465.
[http://dx.doi.org/10.1016/j.dsx.2020.07.054] [PMID: 32771919]
[8]
Hariyanto, T.I.; Kurniawan, A. Anemia is associated with severe coronavirus disease 2019 (COVID-19) infection; Transfus Apher Sci, 2020, p. 102926.
[http://dx.doi.org/10.1016/j.transci.2020.102926] [PMID: 32893135] [PMCID: PMC7452827]
[9]
Sheahan, T.P.; Sims, A.C.; Graham, R.L.; Menachery, V.D.; Gralinski, L.E.; Case, J.B.; Leist, S.R.; Pyrc, K.; Feng, J.Y.; Trantcheva, I.; Bannister, R.; Park, Y.; Babusis, D.; Clarke, M.O.; Mackman, R.L.; Spahn, J.E.; Palmiotti, C.A.; Siegel, D.; Ray, A.S.; Cihlar, T.; Jordan, R.; Denison, M.R.; Baric, R.S. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci. Transl. Med., 2017, 9(396), eaal3653.
[http://dx.doi.org/10.1126/scitranslmed.aal3653] [PMID: 28659436]
[10]
Pizzorno, A.; Padey, B.; Julien, T.; Trouillet-Assant, S.; Traversier, A.; Errazuriz-Cerda, E.; Fouret, J.; Dubois, J.; Gaymard, A.; Lescure, F.X.; Dulière, V.; Brun, P.; Constant, S.; Poissy, J.; Lina, B.; Yazdanpanah, Y.; Terrier, O.; Rosa-Calatrava, M. Characterization and Treatment of SARS-CoV-2 in Nasal and Bronchial Human Airway Epithelia. Cell Rep Med, 2020, 1(4), 100059.
[http://dx.doi.org/10.1016/j.xcrm.2020.100059] [PMID: 32835306]
[11]
Centre for reviews and dissemination (CRD): PROSPERO: inter-nation prospective register for systematic reviews; University of York: UK, 2019.
[12]
Schardt, C.; Adams, M.B.; Owens, T.; Keitz, S.; Fontelo, P. Utilization of the PICO framework to improve searching PubMed for clinical questions. BMC Med. Inform. Decis. Mak., 2007, 7, 16.
[http://dx.doi.org/10.1186/1472-6947-7-16] [PMID: 17573961]
[13]
Polus, S.; Pieper, D.; Burns, J.; Fretheim, A.; Ramsay, C.; Higgins, J.P.T.; Mathes, T.; Pfadenhauer, L.M.; Rehfuess, E.A. Heterogeneity in application, design, and analysis characteristics was found for controlled before-after and interrupted time series studies included in Cochrane reviews. J. Clin. Epidemiol., 2017, 91, 56-69.
[http://dx.doi.org/10.1016/j.jclinepi.2017.07.008] [PMID: 28750849]
[14]
Moher, D.; Liberati, A.; Tetzlaff, J.; Altman, D.G. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J. Clin. Epidemiol., 2009, 62(10), 1006-1012.
[http://dx.doi.org/10.1016/j.jclinepi.2009.06.005] [PMID: 19631508]
[15]
Jadad, A.R.; Moore, R.A.; Carroll, D.; Jenkinson, C.; Reynolds, D.J.; Gavaghan, D.J.; McQuay, H.J. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control. Clin. Trials, 1996, 17(1), 1-12.
[http://dx.doi.org/10.1016/0197-2456(95)00134-4] [PMID: 8721797]
[16]
Sterne, J.A.C.; Savović, J.; Page, M.J.; Elbers, R.G.; Blencowe, N.S.; Boutron, I.; Cates, C.J.; Cheng, H.Y.; Corbett, M.S.; Eldridge, S.M.; Emberson, J.R.; Hernán, M.A.; Hopewell, S.; Hróbjartsson, A.; Junqueira, D.R.; Jüni, P.; Kirkham, J.J.; Lasserson, T.; Li, T.; McAleenan, A.; Reeves, B.C.; Shepperd, S.; Shrier, I.; Stewart, L.A.; Tilling, K.; White, I.R.; Whiting, P.F.; Higgins, J.P.T. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ, 2019, 366, l4898.
[http://dx.doi.org/10.1136/bmj.l4898] [PMID: 31462531]
[17]
Wan, X.; Wang, W.; Liu, J.; Tong, T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med. Res. Methodol., 2014, 14, 135.
[http://dx.doi.org/10.1186/1471-2288-14-135] [PMID: 25524443]
[18]
Wang, Y.; Zhang, D.; Du, G.; Du, R.; Zhao, J.; Jin, Y.; Fu, S.; Gao, L.; Cheng, Z.; Lu, Q.; Hu, Y.; Luo, G.; Wang, K.; Lu, Y.; Li, H.; Wang, S.; Ruan, S.; Yang, C.; Mei, C.; Wang, Y.; Ding, D.; Wu, F.; Tang, X.; Ye, X.; Ye, Y.; Liu, B.; Yang, J.; Yin, W.; Wang, A.; Fan, G.; Zhou, F.; Liu, Z.; Gu, X.; Xu, J.; Shang, L.; Zhang, Y.; Cao, L.; Guo, T.; Wan, Y.; Qin, H.; Jiang, Y.; Jaki, T.; Hayden, F.G.; Horby, P.W.; Cao, B.; Wang, C. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet, 2020, 395(10236), 1569-1578.
[http://dx.doi.org/10.1016/S0140-6736(20)31022-9] [PMID: 32423584]
[19]
Beigel, J.H.; Tomashek, K.M.; Dodd, L.E.; Mehta, A.K.; Zingman, B.S.; Kalil, A.C.; Hohmann, E.; Chu, H.Y.; Luetkemeyer, A.; Kline, S.; Lopez de Castilla, D.; Finberg, R.W.; Dierberg, K.; Tapson, V.; Hsieh, L.; Patterson, T.F.; Paredes, R.; Sweeney, D.A.; Short, W.R.; Touloumi, G.; Lye, D.C.; Ohmagari, N.; Oh, M.D.; Ruiz-Palacios, G.M.; Benfield, T.; Fätkenheuer, G.; Kortepeter, M.G.; Atmar, R.L.; Creech, C.B.; Lundgren, J.; Babiker, A.G.; Pett, S.; Neaton, J.D.; Burgess, T.H.; Bonnett, T.; Green, M.; Makowski, M.; Osinusi, A.; Nayak, S.; Lane, H.C. Remdesivir for the Treatment of Covid-19 - Preliminary Report. N. Engl. J. Med., 2020.
[http://dx.doi.org/10.1056/NEJMoa2007764] [PMID: 32445440]
[20]
Martinez, M.A. Compounds with therapeutic potential against novel respiratory 2019 coronavirus. Antimicrob. Agents Chemother., 2020, 64(5), e00399-e20.
[http://dx.doi.org/10.1128/AAC.00399-20] [PMID: 32152082]
[21]
Agostini, M.L.; Andres, E.L.; Sims, A.C.; Graham, R.L.; Sheahan, T.P.; Lu, X.; Smith, E.C.; Case, J.B.; Feng, J.Y.; Jordan, R.; Ray, A.S.; Cihlar, T.; Siegel, D.; Mackman, R.L.; Clarke, M.O.; Baric, R.S.; Denison, M.R. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) Is mediated by the viral polymerase and the proofreading exoribonuclease. MBio, 2018, 9(2), e00221-e18.
[http://dx.doi.org/10.1128/mBio.00221-18] [PMID: 29511076]
[22]
Morse, J.S.; Lalonde, T.; Xu, S.; Liu, W.R. Learning from the past: possible urgent prevention and treatment options for severe acute respiratory infections caused by 2019-nCoV. ChemBioChem, 2020, 21(5), 730-738.
[http://dx.doi.org/10.1002/cbic.202000047] [PMID: 32022370]
[23]
Williamson, B.N.; Feldmann, F.; Schwarz, B.; Meade-White, K.; Porter, D.P.; Schulz, J.; van Doremalen, N.; Leighton, I.; Kwe Yinda, C.; Pérez-Pérez, L.; Okumura, A.; Lovaglio, J.; Hanley, P.W.; Saturday, G.; Bosio, C.M.; Anzick, S.; Barbian, K.; Cihlar, T.; Martens, C.; Scott, D.P. Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2 bioRxiv, 2020. 2020.04.15.043166

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