Interpreting the impact of hydroxychloroquine prophylaxis on SARS-CoV-2 infection

Sir,

We read with interest the study by Gupta et al1 which presented the findings of SARS-CoV-2 seroprevalence in a large cohort of healthcare workers (HCWs) from a tertiary healthcare facility in north India and examined the effect of various infection control measures. Various strategies were adopted during the SARS-CoV-2 pandemic for reducing transmission as a result of occupational exposure among HCWs. One such strategy included search for medication that would reduce this risk by repurposing of existing drugs2. Among these, hydroxychloroquine (HCQ) has attracted the attention of the scientific community globally, and there are many studies supporting or refuting the efficacy of HCQ in providing effective prophylaxis to those at a high risk of contracting the disease34567.

HCQ prophylaxis was recommended by the ICMR National Task Force for COVID-19 for asymptomatic HCWs exposed to COVID-19 patients and asymptomatic household contacts of COVID-19 patients8. HCQ elevates the pH of endosomes and inhibits SARS-CoV-2 RNA-mediated inflammatory response9.

Gupta et al1 reported that there was no difference in seropositivity between the subgroup of HCWs who did/did not receive the HCQ pre-exposure prophylaxis. Further, around 45 per cent of HCWs who developed antibodies against SARS-CoV-2 in the study were asymptomatic. Since the information on the percentage of HCWs who were on HCQ prophylaxis and asymptomatic despite developing seropositivity is lacking, this precludes commenting on the ability of HCQ in preventing clinically apparent disease in those who took the medication prophylactically. The present study1 also has not taken into account the adequacy of doses of HCQ consumed by the HCWs which is considered to be protective as reported in a case–control investigation conducted by Chatterjee et al10.

Findings from our cross-sectional serosurveillance study11 has suggested that pre-exposure prophylaxis with HCQ may have a role in reducing the vulnerability to infection as depicted by the univariate and multivariate analysis [adjusted odds ratio (OR) 0.55, 95% confidence interval (CI) 0.3-0.9, P=0.047]. The HCWs who took HCQ were divided into four groups – no HCQ and intake of HCQ for <6, 6-10 and >10 weeks. Running the HCQ prophylaxis numbers through logistic regression, for each increasing category of HCQ use, there exists a dose–response OR=0.70 (95% CI 0.50-0.99, P=0.032). This trend is much stronger among the ever-exposed categories (i.e., excluding the never-used HCQ people), per-category OR=0.27 (95% CI 0.11-0.65, P=0.0036)11. Two other observational studies from India1213 have supported the evidence in favour of HCQ pre-exposure prophylaxis. All these observational studies from India taken together enrolled a total of 2660 participants and provided a corroborative evidence of the effectiveness of HCQ prophylaxis for frontline HCWs.

Although Gupta et al1 have reported findings which do not suggest any added benefit of the use of HCQ as prophylaxis among HCWs, analyzing the relationship between the number of doses of HCQ consumed and seropositivity and the severity of disease among those who developed symptoms while on HCQ prophylaxis may be helpful in further refining the analysis. This might be particularly useful in the current situation of ongoing pandemic, with measures such as social distancing becoming increasingly difficult to practise and the vaccine yet to reach the masses.