Response to: “Risks of hydroxychloroquine use for COVID-19 prophylaxis”
Authors: Jane M. Grant-Kels
Journal: Journal of the American Academy of Dermatology (2020)

To the Editor: Thank you to Sachdeva et al1Sachdeva M. Shah M. Ziv M. Leshem E. Dodiuk-Gad R.P. Risks of hydroxychloroquine use for COVID-19 prophylaxis.J Am Acad Dermatol. 2020; 83: e73-e74Abstract Full Text Full Text PDF Scopus (5) Google Scholar for their interest in our letter, "Does hydroxychloroquine combat COVID-19? A timeline of evidence."2Alia E. Grant-Kels J.M. Does hydroxychloroquine combat COVID-19? A timeline of evidence.J Am Acad Dermatol. 2020; 83: e33-e34Abstract Full Text Full Text PDF Scopus (23) Google Scholar As they noted, we reviewed the current literature supporting the preliminary evidence regarding the efficacy and safety of hydroxychloroquine (HCQ) as a treatment or prophylaxis for COVID-19. What we tried to emphasize is that many of these pilot studies, in our opinion, have been done under duress during a pandemic and are flawed. There is a vital need for additional high-quality prospective, randomized, placebo-controlled clinical studies to establish efficacy, safety, and guidelines for the use of HCQ to combat this virus before mainstreaming this therapy.3Taccone F.A. Gorham J. Vincent J.-L. Hydroxychloroquine in the management of critically ill patients with COVID-19: the need for an evidence base.Lancet Respir Med. 2020; https://doi.org/10.1016/S2213-2600(20)30172-7Abstract Full Text Full Text PDF Scopus (91) Google Scholar The oft quoted French studies4Gautret P. Lagier J.C. 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; https://doi.org/10.1016/j.ijantimicag.2020.105949Crossref PubMed Scopus (3759) Google Scholar,5Gautret P. Lagier J.C. Parola P. 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: an observational study.https://www.mediterranee-infection.com/wp-content/uploads/2020/03/COVID-IHU-2-1.pdfDate accessed: April 18, 2020Google Scholar have been touted by the media and have obviously impressed several leaders of governments because these studies suggested that HCQ, a relatively cheap and heretofore readily available medication, could reduce the viral load in patients with COVID-19 and was noted to be especially efficacious if combined with azithromycin. However, the first study4Gautret P. Lagier J.C. 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; https://doi.org/10.1016/j.ijantimicag.2020.105949Crossref PubMed Scopus (3759) Google Scholar was small, with only 20 patients, lacked randomization, and had a short observation period. The second study5Gautret P. Lagier J.C. Parola P. 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: an observational study.https://www.mediterranee-infection.com/wp-content/uploads/2020/03/COVID-IHU-2-1.pdfDate accessed: April 18, 2020Google Scholar lacked a control arm. A recent Chinese trial involving 62 patients6Chen Z. Hu J. Zhang Z. et al.Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial (preprint).medRxiv. 2020; https://doi.org/10.1101/2020.03.22.20040758Crossref Google Scholar showed that HCQ treatment was associated with a shorter time to clinical recovery, manifested by a reduction in temperature and cough, than placebo. However, the participants in this study had mild disease. Therefore, it is not possible to extrapolate these results to those who are critically ill from COVID-19. Questions to be answered include but are not limited to:1.Does the severity of the illness or amount of viral load impact whether the HCQ can be effectual?2.Will HCQ be proven helpful in a larger prospective double-blinded and randomized study?3.What dosage and schedule are the most appropriate in view of the potential for cardiac toxicity?4.What are the guidelines for when this treatment should be initiated? HCQ has been demonstrated to be antiviral but is also known for its successful anti-inflammatory actions that has resulted in it being used extensively in autoimmune diseases; it can significantly decrease the production of cytokines and, in particular, proinflammatory factors.7Adams E.M. Yocum D.E. Bell C.L. Hydroxychloroquine in the treatment of rheumatoid arthritis.Amer J Med. 1983; 75: 321-326Abstract Full Text PDF PubMed Scopus (35) Google Scholar Although the rheumatologic literature has demonstrated that HCQ is less toxic than chloroquine and a very safe medication, prolonged use and overdosing can still cause problems for our patients. Major concerns surround the potential for ventricular arrhythmias, QT prolongation, and other cardiac toxicities. I applaud those at the front line trying desperately to help those suffering with this virus. A recent Wall Street Journal article reported data compiled from the Global Rheumatology Alliance (a coalition of rheumatologists); they reported that more than 5 dozen "people taking hydroxychloroquine and other treatments for chronic rheumatologic diseases have become infected with COVID-19, according to an analysis of emerging data that is a sign the drugs may not protect people from the new coronavirus."8Hopkins J.S. Hydroxychloroquine and Other Autoimmune Drugs Don't Fully Protect Against Coronavirus, Early Data Suggest. Wall Street Journal, April 18, 2020.https://www.wsj.com/articles/hydroxychloroquine-and-other-autoimmune-drugs-dont-fully-protect-against-coronavirus-early-data-suggest-11587222001Date accessed: April 18, 2020Google Scholar These findings cast doubt on the effectiveness of HCQ prophylaxis. Risks of hydroxychloroquine use for COVID-19 prophylaxisJournal of the American Academy of DermatologyVol. 83Issue 1PreviewTo the Editor: We were very pleased to read the article by Alia et al,1 "Does hydroxychloroquine combat COVID-19? A timeline of evidence." After thoroughly summarizing the literature studies on the efficacy and safety of hydroxychloroquine (HCQ), they rightly concluded that there is currently no robust evidence to support prescribing HCQ as a treatment or prophylaxis for COVID-19. As they mentioned, the United States President Donald Trump tweeted on March 21, 2020, that HCQ and azithromycin "taken together, have a real chance to be one of the biggest game changers in the history of medicine" and further urged that these drugs "be put in use IMMEDIATELY. Full-Text PDF