|LETTER TO EDITOR
|Ahead of print publication
Utility of hydroxychloroquine for COVID-19: Are we hoping against hope?
KC Manish1, Shailesh Advani2, Latika Gupta3
1 Department of Internal Medicine, KIST Medical College and Teaching Hospital, Kathmandu, Nepal
2 MBBS Student, Social Behavioural Research Unit, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA
3 Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
|Date of Submission||07-Sep-2020|
|Date of Acceptance||07-Sep-2020|
|Date of Web Publication||08-May-2021|
Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
We read with a great interest the article by Gurjar and Agarwal, which advocates continued preexposure prophylaxis of hydroxychloroquine (HCQ) in high-risk individuals and that timing of administration of HCQ remains crucial for its effectiveness in the management of COVID-19. HCQ works by suppressing the activity of the coronavirus in vitro. HCQ prevents the attachment of the viral spike protein to the gangliosides. It also plays a role in interrupting viral replication by creating a basic pH in the endosomes. In vitro efficacy has been demonstrated for HCQ for various viruses (HIV, dengue, and COVID-19) and it is considered to be the safer immunomodulator in patients with rheumatic diseases (RDs) and concomitant viral infection. Both HCQ and chloroquine (CQ) are equally effective in terms of treatment, but HCQ is associated with fewer side effects and can be used in pregnancy. Despite a promising mechanism of action and acceptable safety profile, unfortunately, evidence of efficacy from most of the clinical trials using HCQ as a treatment for COVID-19 is unconvincing and inconsistent. The only successful trials have been retracted, while other similar ones have demonstrated varying results.,
One randomized clinical trial in 62 patients in China whose findings were supposed to hasten clinical recovery has been criticized for not being peer-reviewed. In an observational study done in over 1400 hospitalized COVID-19 patients in New York, it was found that HCQ was not effective in decreasing the incidence of intubation or mortality when compared with COVID-19 patients who receive a placebo. The UK RECOVERY trial also concluded that HCQ was ineffective in reducing mortality and was associated with risks in hospitalized COVID-19 patients. To date, no precise data on the efficacy and safety of HCQ or CQ in the management of COVID-19 patients have been available. Rheumatologists are well acquiesced and comfortable with the use of HCQ with a large experience base in RDs. The cost, ease of administration, and immunomodulatory action make it a particularly attractive option for treatment. However, the main dictum in medicine is “primum non nocere.” Whether the large experience base of rheumatologists with respect to the safety of HCQ in RDs will translate into similar experience in COVID-19 remains to be proven, particularly so amid concerns of sudden cardiac death in patients with severe COVID-19. Thus, more clinical trials and registry-based data are required in well-stratified subsets of the population with various comorbidities before we can comment on the efficacy and safety of HCQ in the prevention and treatment of coronavirus.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Gurjar M, Agarwal V. Usefulness of hydroxychloroquine for COVID-19: Does answer lie in timing to start? Indian J Rheumatol 2020; 15:249. [Full text]
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;71:732-9. doi:10.1093/cid/ciaa237. PMID: 32150618; PMCID: PMC7108130.
Fantini J, Di Scala C, Chahinian H, Yahi N. Structural and molecular modelling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection. Int J Antimicrob Agents. 2020;55:105960. doi: 10.1016/j.ijantimicag.2020.105960. Epub 2020 Apr 3. PMID: 32251731; PMCID: PMC7128678.
Naghipour S, Ghodousi M, Rahsepar S, and Elyasi S. Repurposing of well-known medications as antivirals: hydroxychloroquine and chloroquine; from HIV-1 infection to COVID-19. Expert Rev Anti Infect Ther. 2020;18:1119-33. doi: 10.1080/14787210.2020.1792291. Epub 2020 Jul 13. PMID: 32631083.
Zhou D, Dai SM, Tong Q. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression. J Antimicrob Chemother. 2020;75:1667-70. doi: 10.1093/jac/dkaa114. PMID: 32196083; PMCID: PMC7184499.
Hernandez AV, Roman YM, Pasupuleti V, Barboza JJ, White CM. Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review. Ann Intern Med. 2020;173:287-296. doi: 10.7326/M20-2496. Epub 2020 May 27. PMID: 32459529.
Kim AHJ, Sparks JA, Liew JW, Putman MS, Berenbaum F, Duarte-García A, et al
. A Rush to Judgment? Rapid Reporting and Dissemination of Results and Its Consequences Regarding the Use of Hydroxychloroquine for COVID-19. Ann Intern Med. 2020;172:819-21. doi: 10.7326/M20-1223. Epub 2020 Mar 30. Erratum in: Ann Intern Med. 2020 Jun 16;172(12):844. PMID: 32227189; PMCID: PMC7138335.
Molina JM, Delaugerre C, Le Goff J, Mela-Lima B, Ponscarme D, Goldwirt L, 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. 2020;50:384. doi: 10.1016/j.medmal.2020.03.006. Epub 2020 Mar 30. PMID: 32240719; PMCID: PMC7195369.
Chen Z, Hu J, Zhang Z, Jiang S, Han S, Yan D, et al
. Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial medRxiv 2020;03:22.20040758; doi:https://doi.org/10.1101/2020.03.22.20040758
Qaseem A, Yost J, Etxeandia-Ikobaltzeta I, Miller MC, Abraham GM, Obley AJ, et al
. Should Clinicians Use Chloroquine or Hydroxychloroquine Alone or in Combination with Azithromycin for the Prophylaxis or Treatment of COVID-19? Living Practice Points from the American College of Physicians (Version 1). Ann Intern Med. 2020;173:137-42. doi: 10.7326/M20-1998. Epub 2020 May 13. Erratum in Ann Intern Med. 2020 May 26; PMID: 32422063; PMCID: PMC7281715.
Torjesen I. Covid-19: Hydroxychloroquine does not benefit hospitalised patients, UK trial finds. BMJ. 2020;369:m2263. doi: 10.1136/bmj.m2263. PMID: 32513810.