Hydroxychloroquine for COVID-19: A review and a debate based on available clinical trials/case studies

Authors

  • Kirtikumar Chandulal Badgujar Assistant Professor, Department of Chemistry, SIES College of Arts Science and Commerce, Sion West, Mumbai 400022, India, Contact no: (+91) 9860180002
  • Ashish B. Badgujar Ophthalmologist, Municipal Eye Hospital, Kamathipura, Mumbai 400008, Maharashtra, India
  • Vikrant P. Patil Consulting Physician, Dwarka Clinic Amalner 425401, Maharashtra, India
  • Dipak V. Dhangar DNB Respiratory medicine resident, Bombay hospital and Medical Research Centre, Mumbai 400020, Maharashtra, India

Abstract

Hydroxychloroquine (HCQ) as a drug grabbed serious attention of whole world in dealing with COVID-19 pandemic. Recently some in-vitro and in-vivo study showing possible inhibition of SARS-CoV-2 by use of HCQ. However at the same time, some case studies showing NO clinical benefit/ poor clinical outcome with substantial detrimental adverse effects by use of HCQ in treatment of coronavirus disease-2019. Thus, the HCQ use (in COVID-19 treatment) is of current international interest, although a consensus has not yet been reached. More evidences are still required to prove efficacy of HCQ against COVID-19. In view of this, the present review highlights the current ongoing research related to use of HCQ in treatment coronavirus disease-2019. The present review will discuss the possible anti-viral mechanism of HCQ, prophylaxis strategy and effect of HCQ against SARS-CoV-2 virus in-vitro study. Further this review also summarizes and debates all available clinical trials/ case studies of HCQ use against COVID-19 (with clinical outcome). Finally possible detrimental adverse effects are also discussed considering the public health and pharmacovigilance concern.

Keywords: Potency of hydroxychloroquine; COVID-19; Coronavirus disease-2019; Clinical trials; SARS-CoV-2; Adverse effects of hydroxychloroquine; Pharmacovigilance concern

Keywords:

hydroxychloroquine, COVID-19, Coronavirus disease-2019, SARS-CoV-2

DOI

https://doi.org/10.22270/jddt.v10i3.4110

Author Biographies

Kirtikumar Chandulal Badgujar, Assistant Professor, Department of Chemistry, SIES College of Arts Science and Commerce, Sion West, Mumbai 400022, India, Contact no: (+91) 9860180002

Assistant Professor, Department of Chemistry, SIES College of Arts Science and Commerce, Sion West, Mumbai 400022, India, Contact no: (+91) 9860180002

Ashish B. Badgujar, Ophthalmologist, Municipal Eye Hospital, Kamathipura, Mumbai 400008, Maharashtra, India

Ophthalmologist, Municipal Eye Hospital, Kamathipura, Mumbai 400008, Maharashtra, India

Vikrant P. Patil, Consulting Physician, Dwarka Clinic Amalner 425401, Maharashtra, India

Consulting Physician, Dwarka Clinic Amalner 425401, Maharashtra, India

Dipak V. Dhangar, DNB Respiratory medicine resident, Bombay hospital and Medical Research Centre, Mumbai 400020, Maharashtra, India

DNB Respiratory medicine resident, Bombay hospital and Medical Research Centre, Mumbai 400020, Maharashtra, India

References

Andersen KG, Rambaut A, Lipkin W, et al. The proximal origin of SARS-CoV-2. Nat Med, 2020. Accepted manuscript https://doi.org/10.1038/s41591-020-0820-9

Badgujar KC, Patil DV, Dhangar DV, Patil VP, Badgujar AB. COVID-19: Epidemiology, clinical characteristics and potential possible treatment based on available studies, submitted manuscript, Coronaviruses Journal, Bentham Science.

https://www.worldometers.info/coronavirus/

https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-daily-roundup-march-30-2020

Chen J, Liu D, Liu L, et al. A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19). J Zhejiang Univ (Med Sci) 2020; published online March 3. Pre-print DOI:10.3785/j.issn.1008-9292.2020.03.03 DOI: http://www.zjujournals.com/med/EN/10.3785/j.issn.1008-9292.2020.03.03

Gautret P, Lagier JC, Parola P, 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. Accepted manuscript DOI:10.1016/j.ijantimicag.2020.105949

Molina JM, Delaugerre C, Le Goff J, et al. No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection. Med Mal Infect. Accepted manuscript 2020. DOI:10.1016/j.medmal.2020.03.006.

Chen Z, Hu J, Zhang Z, et al. Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. Pre-print medRxiv 2020; published online March 31. DOI:10.1101/2020.03.22.20040758

Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Sevestre J, et al. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: a pilot observational study, 2020, Travel Medicine and Infectious disease. Accepted manuscript 2020 DOI: https://doi.org/10.1016/j.tmaid.2020.101663

Chorin E, Dai M, Shulman E, Wadhwani L, Cohen RB, Barbhaiya C, et al. The QT Interval in Patients with SARS-CoV-2 Infection Treated with Hydroxychloroquine/Azithromycin. Pre-print 2020 DOI: doi: https://doi.org/10.1101/2020.04.02.20047050

Sperber K, Quraishi H, Kalb TH, Panja A, Stecher V, Mayer L. Selective regulation of cytokine secretion by HCQ: inhibition of interleukin 1 alpha (IL-1-alpha) and IL-6 in human monocytes and T cells. J Rheumatol 1993;20:803–808

Chang TC, Wang LF, Lin YS, Yang CS, Yu CY, Lin YL. 25: HCQ activates host antiviral innate immunity. Cytokine 2014;70:33-34

Sperber K, Hom C, Chao P, Shapiro D, Ash J, Aberientos C. Systematic Review of HCQ Use in Pregnant Patients with Autoimmune Diseases. Pediatric Rheumatol. 2009;7: 910-915. DOI: 10.1186/1546-0096-7-9

Sharma OP. Effectiveness of CQ and HCQ in treating selected patients with sarcoidosis with neurological involvement. Archives of Neurology, 1998;55:1248-1254. DOI: 10.1001/archneur.55.9.1248

Runge LA. Risk/benefit analysis of HCQ sulfate treatment in rheumatoid arthritis. The American Journal of Medicine 1983;75:52-56. DOI: 10.1016/0002-9343(83)91271-8

Yun D, Silverberg NB, Stein SL. Alopecia areata treated with HCQ: A retrospective study of nine pediatric cases. Pediatric Dermatology 2018;35:361-365.

Antón Vázquez V, Pascual L, Corominas H, Torrecilla GI. Relapsed HCQ induced thrombocytopenia in a systemic lupus erythematosus patient. Reumatologia Clinica, 2017;13:294-296. DOI: 10.1016/j.reuma.2016.04.008

Petri M. Thrombosis and systemic lupus erythematosus: the Hopkins Lupus Cohort perspective. Scand J Rheumatol 1996;25:191-193 DOI: 10.3109/03009749609069986

Rahim R, Strobl JS. HCQ, CQ, and all-trans retinoic acid regulate growth, survival, and histone acetylation in breast cancer cells. Anticancer Drugs 2009;20:736-745

Haque A, Hober D, Blondiaux J. Ebola and marburg: Addressing Therapeutic Options for Ebola Virus Infection in Current and Future Outbreaks. Antimicrobial agents and Chemotherapy. 2015;59: 5892-5902. DOI: 10.1128/AAC.01105-15

Kumar A, Liang B, Aarthy M, Singh SK, Garg N, Mysorekar IU, HCQ Inhibits Zika Virus NS2B-NS3 Protease ACS Omega. 2018;31:18132-18141.DOI: 10.1021/acsomega.8b01002

Romanelli F, Smith KM, Hoven AD. CQ and HCQ as inhibitors of human immune-deficiency virus (HIV-1) activity. Curr Pharm Des. 2004;21:2643-2648.

Wang L, Lin Y, Huang N, Yu C, Tsai W, Chen J, Kubota T, Matsuoka M, Chen S, Yang C et al. HCQ-Inhibited Dengue Virus Is Associated with Host Defense Machinery. J. Interferon Cytokine Res. 2015, 35, 143-156. DOI: 10.1089/jir.2014.0038.

Pandya S. Methotrexate and HCQ combination therapy in chronic chikungunya arthritis: a 16 week study Indian Journal of Rheumatology 2008;3:93-97

Chandramohan M, Vivekananthan CS, Sivakumar D, Selvam P et al., Preliminary report of anti-hepatitis C virus activity of CQ and HCQ in huh-5-2 cell line. DOI: 10.4103/0250-474X.27842

Dyall J, Coleman CM, Hart BJ, Venkataraman T, Holbrook MR, Kindrachuk J, Johnson RF, Olinger GG Jr, Jahrling PB, Laidlaw M, Johansen LM, Lear-Rooney CM, Glass PJ, Hensley LE, Frieman MB Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother. 2014 Aug; 58(8):4885-93

Yao X, Ye F. Zhang M, Cui C, Huang B, Niu P. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of HCQ for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. Accepted manuscript 2020 . DOI:10.1093/cid/ciaa237.

Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of chloroquine on viral infections: an old drug against today’s diseases? THE LANCET Infectious Diseases 2003;3;722-727

Liu J, Cao R, Xu M, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov 2020; 6: 16-22

Haibo Zhang, Penninger JM, Li Y, Zhong N,Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020; 46(4): 586-590.

Chiang G, Sassaroli M, Louie M, Chen H, Stecher VJ, and Sperber K. Inhibition of HIV-1 replication by hydroxychloroquine: mechanism of action and comparison with zidovudine. Clin Ther. 1996; 18:1080-1092.

Paton NI, Aboulhab J, Karim F. Hydroxychloroquine, hydroxycarbamide, and didanosine as economic treatment for HIV-1. Lancet 2002; 359: 1667-1668.

Tang W, Cao Z, Han M, Wang Z, Chen J, Sun W, et al. Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial. doi: Pre-print 2020 https://doi.org/10.1101/2020.04.10.20060558

Mahévas M, Tran VT, Roumier MR, Chabrol AC, Paule R, Guillaud C. No evidence of clinical efficacy of hydroxychloroquine in patients hospitalised for COVID-19 infection and requiring oxygen: results of a study using routinely collected data to emulate a target trial. 2020 pre-print, doi: https://doi.org/10.1101/2020.04.10.20060699

Magagnoli J, Narendran S, Hardin JW, Pereira F, Sutton S, Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19. 2020. doi: pre-print 2020 https://doi.org/10.1101/2020.04.16.20065920

Principi N, Esposito S. Chloroquine or hydroxychloroquine for prophylaxis of COVID-19, The Lancet, Accepted paper, 2020, DOI:https://doi.org/10.1016/S1473-3099(20)30296-6

https://www.mohfw.gov.in/pdf/AdvisoryontheuseofHydroxychloroquinasprophylaxisforSARSCoV2infection.pdf

Owens B. Excitement around hydroxychloroquine for treating COVID-19 causes challenges for rheumatology, The Lancet Rheumatology. Accepted manuscript 2020, DOI:https://doi.org/10.1016/S2665-9913(20)30089-8

https://www.newsweek.com/hydroxychloroquine-coronavirus-france-heart-cardiac-1496810

https://www.newsweek.com/swedish-hospitals-chloroquine-covid-19-side-effects-1496368

https://www.axios.com/chloroquine-coronavirus-death-09c91a91-4fe7-472c-9de9-79b890aa8fff.html

Lover AA. Quantifying treatment effects of hydroxychloroquine and azithromycin for COVID-19: a secondary analysis of an open label non-randomized clinical trial (Gautret et al, 2020). 2020 Pre-print doi: https://doi.org/10.1101/2020.03.22.20040949

Hancox JC. AZT, cardiovascular risks, QTc interval prolongation and regulatory issues: A narrative review based on the study of case reports. Ther Adv Infect Dis. 2013;1:155-165.doi: 10.1177/2049936113501816

Prakash, B, Kumar H, Palaniswami S, Lakshman B. Ocular side effects of systemic drugs used in dermatology. Indian Journal of Dermatology, 2019;64:423-430

Stein M, Bell MJ, Ang LC. HCQ neuromyotoxicity. J. Rheumatol. 2000 Dec; 27(12):2927-31.

Srinivasa A, Tosounidou S, Gordon C. Increased incidence of gastrointestinal side effects in patients taking HCQ: A brand-related issue? Journal of Rheumatology, 2017;44:368. DOI: 10.3899/jrheum.161063

Djennane M, Tablit I, Billhot M, Banal F. Acute generalized exanthematic pustulosis induced by HCQ: Case report. Revue de Medecine Interne 2010;31:e7-e8. DOI: 10.1016/j.revmed.2009.03.350

Mustafa U, Mediha A, Engin G. Hypoglycemia Induced by HCQ in a Patient Treated for Rheumatoid Arthritis Journal of Clinical Rheumatology 2011;17:46-47 doi: 10.1097/RHU.0b013e3182098e1f

Leckie MJ, Rees RG. Stevens - Johnson syndrome in association with HCQ treatment for rheumatoid arthritis. Rheumatology, 2002; 41:473-474, https://doi.org/10.1093/rheumatology/41.4.473

https://www.rxlist.com/plaquenil-side-effects-drug-center.htm#consumer (Allergic action: Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat

Published

2020-05-15
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How to Cite

1.
Badgujar KC, Badgujar AB, Patil VP, Dhangar DV. Hydroxychloroquine for COVID-19: A review and a debate based on available clinical trials/case studies. J. Drug Delivery Ther. [Internet]. 2020 May 15 [cited 2026 Jan. 22];10(3):304-11. Available from: https://jddtonline.info/index.php/jddt/article/view/4110

How to Cite

1.
Badgujar KC, Badgujar AB, Patil VP, Dhangar DV. Hydroxychloroquine for COVID-19: A review and a debate based on available clinical trials/case studies. J. Drug Delivery Ther. [Internet]. 2020 May 15 [cited 2026 Jan. 22];10(3):304-11. Available from: https://jddtonline.info/index.php/jddt/article/view/4110