Hydroxychloroquine in the treatment of COVID-19 disease: a systematic review and meta-analysis

  • Amahirany Manzo-Toledo Facultad de Odontología, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca, México https://orcid.org/0000-0002-0457-092X
  • Rafael Torres-Rosas Laboratorio de Inmunología, Centro de Estudios en Ciencias de la Salud y la Enfermedad, Facultad de Odontología, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca, México
  • Hugo Mendieta-Zerón Facultad de Medicina, Universidad Autónoma del Estado de México, Toluca de Lerdo, México https://orcid.org/0000-0003-3492-8950
  • Lourdes Arriaga-Pizano Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades Bernardo Sepúlveda, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México
  • Liliana Argueta-Figueroa Cátedras-Conacyt - Facultad de Odontología, Universidad Autónoma Benito Juárez de Oaxaca, México
DOI: https://doi.org/10.13181/mji.oa.205012
Keywords: COVID-19, hydroxychloroquine, mortality, SARS-CoV-2
Abstract viewed: 1581 times
PDF downloaded: 990 times
HTML downloaded: 234 times
EPUB downloaded: 156 times

Abstract

BACKGROUND Given the urgency of finding a specific treatment for coronavirus disease 2019 (COVID-19), several approaches have been carried out, including the use of chloroquine (CQ) and hydroxychloroquine (HCQ). This study was aimed to systematically evaluate the available evidence on the effectiveness of HCQ in the treatment of COVID-19 disease.

METHODS We searched 3 databases (PubMed, Google Scholar, and ClinicalTrials) until May 31, 2020 for clinical studies in patients diagnosed with COVID-19 comparing conventional treatment with and without HCQ combined with or without azithromycin. The risk of bias assessment and quality evaluation was carried out according to the Cochrane recommendations.

RESULTS 5 articles (1 randomized clinical trial [RCT], 1 non-RCT, and 3 cohort studies) were included. The main outcome measure in 2 articles was the virological conversion determined by reverse transcription-polymerase chain reaction; however, the findings of both studies were contrary. The main objective of the other studies was to determine the effects of HCQ on COVID-19 mortality, and the studies showed similar results. In general, the studies showed methodological limitations, risk of bias, and variable quality. A meta-analysis from 2,041 patients showed the odds ratio of mortality for patients having HCQ and standard care was 1.38 (95% CI 0.93–2.04).

CONCLUSIONS Considering the limited data available and the very low-to-moderate quality of the studies included in this systematic review, the evidence suggests that the HCQ administration does not decrease the risk of death from COVID-19.

References

  1. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72,314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239−42. https://doi.org/10.1001/jama.2020.2648

  2. Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020;71(15):732−9. https://doi.org/10.1093/cid/ciaa237

  3. Cumpston M, Li T, Page MJ, Chandler J, Welch VA, Higgins JP, et al. Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev. 2019;10:ED000142. https://doi.org/10.1002/14651858.ED000142

  4. Sterne JA, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898. https://doi.org/10.1136/bmj.l4898

  5. Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919. https://doi.org/10.1136/bmj.i4919

  6. Schünemann H, Brożek J, Guyatt G, Oxman A, editors. GRADE handbook [Internet]. 2013 [cited 2020 Apr 10]. Available from: https://gdt.gradepro.org/app/handbook/handbook.html.

  7. Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020;56(1):105949. https://doi.org/10.1016/j.ijantimicag.2020.105949

  8. Tang W, Cao Z, Han M, Wang Z, Chen J, Sun W, et al. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. BMJ. 2020;369:m1849. https://doi.org/10.1136/bmj.m1849

  9. Mahévas M, Tran VT, Roumier M, Chabrol A, Paule R, Guillaud C, et al. Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data. BMJ. 2020;369:m1844. https://doi.org/10.1136/bmj.m1844

  10. Rosenberg ES, Dufort EM, Udo T, Wilberschied LA, Kumar J, Tesoriero J, et al. Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York State. JAMA. 2020;323(24):2493-502. https://doi.org/10.1001/jama.2020.8630

  11. Geleris J, Sun Y, Platt J, Zucker J, Baldwin M, Hripcsak G, et al. Observational study of hydroxychloroquine in hospitalized patients with Covid-19. N Engl J Med. 2020;382:2411-8. https://doi.org/10.1056/NEJMoa2012410

  12. Sharma A. Chloroquine paradox may cause more damage than help fight COVID-19. Microbes Infect. 2020;22(4):154-6. https://doi.org/10.1016/j.micinf.2020.04.004

  13. Shibata M, Aoki H, Tsurumi T, Sugiura Y, Nishiyama Y, Suzuki S, et al. Mechanism of uncoating of influenza B virus in MDCK cells: action of chloroquine. J Gen Virol. 1983;64(Pt 5):1149-56. https://doi.org/10.1099/0022-1317-64-5-1149

  14. Vigerust DJ, McCullers JA. Chloroquine is effective against influenza A virus in vitro but not in vivo. Influenza Other Respir Viruses. 2007;1(5-6):189-92. https://doi.org/10.1111/j.1750-2659.2007.00027.x

  15. Helal GK, Gad MA, Abd-Ellah MF, Eid MS. Hydroxychloroquine augments early virological response to pegylated interferon plus ribavirin in genotype-4 chronic hepatitis C patients. J Med Virol. 2016;88(12):2170-8. https://doi.org/10.1002/jmv.24575

  16. Vaccari M, Fenizia C, Ma ZM, Hryniewicz A, Boasso A, Doster MN, et al. Transient increase of interferon-stimulated genes and no clinical benefit by chloroquine treatment during acute simian immunodeficiency virus infection of macaques. AIDS Res Hum Retroviruses. 2014;30(4):355-62. https://doi.org/10.1089/aid.2013.0218

  17. Jacobson JM, Bosinger SE, Kang M, Belaunzaran-Zamudio P, Matining RM, Wilson CC, et al. The effect of chloroquine on immune activation and interferon signatures associated with HIV-1. AIDS Res Hum Retroviruses. 2016;32(7):636-47. https://doi.org/10.1089/aid.2015.0336

  18. Routy JP, Angel JB, Patel M, Kanagaratham C, Radzioch D, Kema I, et al. Assessment of chloroquine as a modulator of immune activation to improve CD4 recovery in immune nonresponding HIV-infected patients receiving antiretroviral therapy. HIV Med. 2015;16(1):48-56. https://doi.org/10.1111/hiv.12171

  19. Keyaerts E, Li S, Vijgen L, Rysman E, Verbeeck J, Van Ranst M, et al. Antiviral activity of chloroquine against human coronavirus OC43 infection in newborn mice. Antimicrob Agents Chemother. 2009;53(8):3416-21. https://doi.org/10.1128/AAC.01509-08

  20. Deeks J, Fellow J, Altman D. Analysing data and undertaking meta‐analyses. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al, editors. Cochrane handbook for systematic reviews of interventions version 6.0 (updated July 2019). Cochrane; 2019 [cited 2020 Feb 21]. p. 243-96.

  21. White IR, Royston P. Imputing missing covariate values for the Cox model. Stat Med. 2009;28(15):1982-98. https://doi.org/10.1002/sim.3618

  22. Pankratz VS, de Andrade M, Therneau TM. Random-effects Cox proportional hazards model: general variance components methods for time-to-event data. Genet Epidemiol. 2005;28(2):97-109. https://doi.org/10.1002/gepi.20043

  23. Million M, Lagier JC, Gautret P, Colson P, Fournier PE, Amrane S, et al. Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: a retrospective analysis of 1061 cases in Marseille, France. Travel Med Infect Dis. 2020;35:101738. https://doi.org/10.1016/j.tmaid.2020.101738

  24. Wolfe F, Marmor MF. Rates and predictors of hydroxychloroquine retinal toxicity in patients with rheumatoid arthritis and systemic lupus erythematosus. Arthritis Care Res. 2010;62(6):775−84. https://doi.org/10.1002/acr.20133

  25. National Institues of Health, U.S. Department of Health and Human Services. NIH halts clinical trial of hydroxychloroquine: study shows treatment does no harm, but provides no benefit [Internet]. 2020 [cited 2020 Aug 14]. Available from: https://www.nih.gov/news-events/news-releases/nih-halts-clinical-trial-hydroxychloroquine.

  26. Pan H, Peto R, Karim QA, Alejandria M, Henao-Restrepo AM, García CH, et al. Repurposed antiviral drugs for COVID-19 -interim WHO SOLIDARITY trial results. medRxiv. 2020:2020.10.15.20209817.

  27. Meo SA, Klonoff DC, Akram J. Efficacy of chloroquine and hydroxychloroquine in the treatment of COVID-19. Eur Rev Med Pharmacol Sci. 2020;24(8):4539−47. https://doi.org/10.26355/eurrev_202004_21038

  28. Sarma P, Kaur H, Kumar H, Mahendru D, Avti P, Bhattacharyya A, et al. Virological and clinical cure in COVID-19 patients treated with hydroxychloroquine: a systematic review and meta-analysis. J Med Virol. 2020;92(7):776−85. https://doi.org/10.1002/jmv.25898

  29. Deeks JJ, Altman DG, Bradburn MJ. Statistical methods for examining heterogeneity and combining results from several studies in meta-analysis. In: Egger M, Smith GD, Altman DG, editors. Systematic reviews in health care: meta‐analysis in context. 2nd ed. London: BMJ Publishing Groups; 2001. p. 285−312. https://doi.org/10.1002/9780470693926.ch15

  30. Shah S, Das S, Jain A, Misra DP, Negi VS. A systematic review of the prophylactic role of chloroquine and hydroxychloroquine in coronavirus disease-19 (COVID-19). Int J Rheum Dis. 2020;23(5):613−9. https://doi.org/10.1111/1756-185X.13842

Published
2021-01-26
How to Cite
1.
Manzo-Toledo A, Torres-Rosas R, Mendieta-Zerón H, Arriaga-Pizano L, Argueta-Figueroa L. Hydroxychloroquine in the treatment of COVID-19 disease: a systematic review and meta-analysis. Med J Indones [Internet]. 2021Jan.26 [cited 2024Apr.26];30(1):20–32. Available from: http://mji.ui.ac.id/journal/index.php/mji/article/view/5012
Issue
Vol. 30 No. 1 (2021): March
Section
Clinical Research

Copyright (c) 2021 Amahirany Manzo-Toledo, Rafael Torres-Rosas, Hugo Mendieta-Zerón, Lourdes Arriaga-Pizano, Liliana Argueta-Figueroa

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Authors who publish with Medical Journal of Indonesia agree to the following terms:

  1. Authors retain copyright and grant Medical Journal of Indonesia right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial License that allows others to remix, adapt, build upon the work non-commercially with an acknowledgment of the work’s authorship and initial publication in Medical Journal of Indonesia.
  2. Authors are permitted to copy and redistribute the journal's published version of the work non-commercially (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in Medical Journal of Indonesia.