Authors’ response

We thank Yadav and Madkaikar for reading our article with interest and commenting regarding prophylactic use of hydroxychloroquine sulphate (HCQS) in asymptomatic healthcare workers (HCWs). Yadav et al1 raised a relevant point that perhaps the HCQS prophylaxis reduced or abated symptomatic disease, the duration and dosage of HCQS prophylaxis influenced the outcome.

We reported that 769 HCWs received HCQS prophylaxis and 99 of 769 were seropositive compared to 388 of 2970 HCWs who did not receive HCQS prophylaxis (P=0.89)2. On analyzing the correlation of symptomatic disease with HCQS prophylaxis, it was found that among the seropositive HCWs, 70.77 per cent (70/99) of those who received HCQS prophylaxis were symptomatic compared to 52.3 per cent (203/388) HCWs who were not on HCQS prophylaxis (P<0.01). In our study, higher numbers of HCWs with HCQS were symptomatic compared to those who did not take the HCQS prophylaxis, and thus, the HCQS prophylaxis did not seem to improve upon the symptomatic status in HCWs2. Yadav et al1 have reported the presence of symptoms in comparable numbers of patients with or without HCQS prophylaxis (39.78 vs. 35.3%; P=0.3).

Another relevant comment was on the correlation of the duration and dosage of HCQS prophylaxis with the likelihood of seropositivity or RT-PCR–positive SARS-CoV-2 infection. In this regard, Chatterjee et al3 have reported a relatively fewer numbers of HCWs infected with SARS-CoV-2 in the subgroup who received more than six doses of HCQS (n=12), whereas the difference in incidence was not different in those who received less doses of HCQS. Goenka et al4 reported lower seroprevalence for SARS-CoV-2 in those who received adequate, i.e., more than six doses of HCQS versus rest of the HCWs. However, we have concerns regarding the interpretations in the study by Yadav et al1. First of all, the data shown for comparison within seropositive subjects (n=55) are for HCQS exposure of <4h versus >4h versus no HCQS, whereas the HCWs with HCQS prophylaxis were otherwise divided into those with <6, 6-10 and >10 wk of HCQS. The criterion on how the patients were divided into HCQS exposure of <4h versus >4h is not mentioned in this paper. Further, the data on dosage and duration of HCQS prophylaxis were not available in 36.2 per cent (101/279) of the HCWs in this study who were excluded from the subgroup analysis. As a result, the patients in the seropositive group on HCQS prophylaxis (<22; exact numbers not mentioned) in this study were perhaps too few for a meaningful subgroup analysis when split into three further subgroups2.

A few randomized controlled trials of HCQS as pre or post-exposure prophylaxis for COVID-19 suggested that HCQS did not significantly reduce laboratory confirmed COVID-19 or COVID-19–compatible illness among HCWs5,6,7. Kumar et al8 and Kashour et al9 in their meta-analysis studies also concluded that HCQS therapy for COVID-19 lacked efficacy in reducing short-term mortality in patients hospitalized with COVID-19 or risk of hospitalization in outpatients with COVID-19 and was associated with an increase in mortality and the negative effects were more pronounced in the hospitalized patients.

On March 28, 2020, the Food and Drugs Administration (FDA) granted emergency use authorization (EUA) for hydroxychloroquine as a COVID-19 prophylaxis. The emerging scientific data suggest that dosing for HCQS is unlikely to kill or inhibit the SARS-CoV-2 virus, and on June 15, 2020, the FDA revoked EUA to use HCQS and chloroquine to treat COVID-19 in hospitalized patients5,6,7,8,9,10. FDA also cautions against the use of HCQS for COVID-19 outside of the hospital setting or in a clinical trial due to risk of heart rhythm problems8,9,10. Therefore, use of HCQS for its potential benefits in COVID-19 does not outweigh its known and potential risks.