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Usefulness of hydroxychloroquine for COVID-19: Does answer lie in timing to start?

1 Department of Critical Care Medicine, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
2 Department of Clinical Immunology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Date of Submission26-Jun-2020
Date of Acceptance26-Jun-2020
Date of Web Publication20-Jul-2020

Correspondence Address:
Mohan Gurjar,
Department of Critical Care Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow - 226 014, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/injr.injr_167_20

How to cite this URL:
Gurjar M, Agarwal V. Usefulness of hydroxychloroquine for COVID-19: Does answer lie in timing to start?. Indian J Rheumatol [Epub ahead of print] [cited 2020 Aug 7]. Available from:

To Editor,

Two recent studies on the efficacy of hydroxychloroquine (HCQ) for COVID-19 published in The New England Journal of Medicine, one large observational study for the treatment of hospitalized patients by Geleris et al. and another randomized controlled trial (RCT) as postexposure prophylaxis by Boulware et al., did not show beneficial effect on the use of HCQ either as treatment or as postexposure prophylaxis, when compared to standard of care or placebo, respectively.[1],[2] The results of these studies are more provocative than definitive.

In fact, the results of RCT of HCQ for postexposure prophylaxis with the primary outcome of incidence of either laboratory confirmed or illness compatible with COVID-19 within 14 days, should be interpreted with caution, as above 80% of participants were enrolled after 24 h of exposure, including one-third on the 4th day (means one-third received drug at least after 96 h of exposure). By delaying in drug administration, severe acute respiratory syndrome-coronavirus-2 had already replicated and affected target cells in the body, if incubated.In vitro studies suggest that delaying in drug administration even by 2–5 h reduces the inhibition of virus replication.[3],[4] In the RCT, results might be simply affected by the timing of the drug after exposure. Almost half of the participants who developed illness had onset by the 5th day of either HCQ or placebo, while cumulative incidence of illness among placebo group showed a trend of continuous rise, higher than HCQ group, at days 10 and 14.

Considering the risk–benefit ratio and evidences fromin vitro studies, the use of HCQ could be continued as preexposure prophylaxis, especially in high-risk individuals including health-care personnel, as recommended by the Indian Council of Medical Research, till we have more evidences.[5]

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Conflicts of interest

There are no conflicts of interest.

  References Top

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.  Back to cited text no. 1
Boulware DR, Pullen MF, Bangdiwala AS, Pastick KA, Lofgren SM, Okafor EC, et al. A randomized trial of hydroxychloroquine as postexposure prophylaxis for COVID-19. N Engl J Med 2020. doi: 10.1056/NEJMoa2016638. [Online ahead of print].  Back to cited text no. 2
Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek TG, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J 2005;2:69.  Back to cited text no. 3
Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020;30:269-71.  Back to cited text no. 4
Indian Council of Medical Research: Recommendation for Empiric use of Hydroxychloroquine for Prophylaxis of SARS-CoV-2 Infection; 22nd March, 2020. Available from: [Last accessed on 2020 Jun 25].  Back to cited text no. 5


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