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. 2021 Aug 5;14(9):1161–1163. doi: 10.1016/j.jiph.2021.08.001

Hydroxychloroquine Pre-Exposure Prophylaxis for COVID-19 in Healthcare Workers from India: A Meta-Analysis

Raphael B Stricker 1,, Melissa C Fesler 1
PMCID: PMC8340552  PMID: 34391171

Abstract

To date, the COVID-19 pandemic has resulted in more than 200 million cases of SARS-CoV-2 infection and more than four million deaths world-wide. 1 Although novel COVID-19 vaccines have become clinically available, the safety and efficacy of these vaccines remains open to question. 2 Alternate approaches to prevention of disease have received little attention, and one medication, hydroxychloroquine (HCQ), has been attacked and dismissed based on flawed studies and political controversy that obscured the value of this treatment as pre-exposure prophylaxis (PrEP) for SARS-CoV-2 infection.

Keywords: COVID-19, SARS-CoV-2, Pre-exposure prophylaxis, Hydroxychloroquine, Vaccine


To date, the COVID-19 pandemic has resulted in more than 200 million cases of SARS-CoV-2 infection and more than four million deaths world-wide [1]. Although novel COVID-19 vaccines have become clinically available, the safety and efficacy of these vaccines remains open to question [2]. Alternate approaches to prevention of disease have received little attention, and one medication, hydroxychloroquine (HCQ), has been attacked and dismissed based on flawed studies and political controversy that obscured the value of this treatment as pre-exposure prophylaxis (PrEP) for SARS-CoV-2 infection.

A British study of 120,075 healthcare workers (HCWs) found that these subjects had a 7–8 fold greater risk of developing severe COVID-19 compared to non-HCWs [3]. With this background, the Indian Council of Medical Research (ICMR) National Taskforce for COVID-19 formulated guidelines for weekly HCQ PrEP in high-risk HCWs [4]. We used internet search engines to identify 11 cohort studies of weekly HCQ PrEP in HCWs from India based on the ICMR protocol [[5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15]]. These case-control studies enrolled a total of 7616 high-risk HCWs who were tested for SARS-CoV-2 infection as an endpoint after varying lengths of time following weekly HCQ PrEP or no treatment.

We have performed a preliminary meta-analysis of these studies, as shown in Table 1 . In the 11 studies that included HCWs who used any HCQ PrEP, the infection rate was significantly decreased (RR 0.56, p = 0.0040). In the five studies that included HCWs who took at least six doses of weekly HCQ PrEP, the infection rate was reduced even further (RR 0.25, p < 0.0001). The uniform ICMR treatment protocol used in these studies argues against bias related to variations in dosing of HCQ. There were minimal adverse events reported in the HCQ-treated subjects, consistent with other safety reports for HCQ use in COVID-19 trials [16,17].

Table 1.

HCQ PrEP studies in healthcare workers from India.

Study HCQ (n) No HCQ (n) RR (95% CI) P-valuea
1. Chatterjee et al., 2020 365 386
 HCQ any dose infection 172 193 0.90 (0.60-1.35) 0.62
 HCQ ≥ 6 doses infection 12/68 0.04 (0.01-0.16) <0.0001
2. Bhattacharya et al., 2020 54 52
 HCQ any dose infection 4 20 0.19 (0.07-0.53) 0.0013
 HCQ ≥ 6 doses infection NA
3. Khurana et al., 2021 90 91
 HCQ any dose infection 54 40 1.36 (1.02-1.82) 0.033
 HCQ ≥ 6 doses infection 6/22 0.62 (0.30-1.28) 0.19
4. Goenka et al., 2020 237 885
 HCQ any dose infection 19 115 0.62 (0.39-0.98) 0.041
 HCQ ≥ 6 doses infection 1/77 0.10 (0.01-0.71) 0.021
5. Yadav et al., 2021 178 221
 HCQ any dose infection 17 27 0.78 (0.44-1.39) 0.40
 HCQ ≥ 6 doses infection 6/125 0.39 (0.17-0.93) 0.033
6. Kadnur et al., 2020 248 86
 HCQ any dose infection 2 5 0.14 (0.03-0.70 0.017
 HCQ ≥ 6 doses infection NA
7. Dev et al., 2021 260 499
 HCQ any dose infection 155 351 0.74 (0.61-0.90) 0.0024
HCQ > 6 doses infection NA
8. Mathai et al., 2020 491 113
 HCQ any dose infection 10 22 0.10 (0.05-0.21) <0.0001
 HCQ ≥ 6 doses infection NA
9. Datta et al., 2020 146 135
 HCQ any dose infection 16 19 0.78 (0.42-1.45) 0.43
 HCQ ≥ 6 doses infection NA
10. Behera et al., 2021 186 186
 HCQ any dose infection 7 12 0.56 (0.19-1.63) 0.29
 HCQ ≥ 6 doses infection NA
11. Badyal et al., 2021 1,234 1,473
 HCQ any dose infection 415 611 0.81 (0.73-0.90) <0.0001
 HCQ ≥ 6 doses infection 247/981 0.28 (0.21-0.37) <0.0001
Total
 HCQ any dose 3,489 4,127
Infection 871 (25%) 1,428 (35%) 0.56 (0.37-0.83) 0.0040
 HCQ ≥ 6 doses 1,273
Infection 272 (21%) 0.25 (0.13-0.50) <0.0001

HCQ, hydroxychloroquine; PrEP, pre-exposure prophylaxis; NA, not available; RR, adjusted risk ratio; CI, confidence interval.

a

Treated subjects versus untreated controls.

Our meta-analysis suggests that weekly HCQ PrEP is safe and effective in preventing COVID-19 in a high-risk group of HCWs. Although severity of disease was not reported for infected subjects in most of the studies, prevention of infection implies a lower risk of severe illness in treated HCWs. It is important to recognize that these studies exclusively analyzed HCQ PrEP and excluded HCQ post-exposure prophylaxis (PEP) or treatment of SARS-CoV-2-infected individuals. Lumping of these groups in prior studies has resulted in flawed analysis and inaccurate conclusions about the safety and efficacy of HCQ PrEP [18]. Although the cohort studies have limitations in terms of retrospective design and subject homogeneity, they suggest that HCQ PrEP could serve as a stop-gap approach to COVID-19 prevention until universal vaccination is achieved. Further randomized trials of HCQ PrEP should be conducted to evaluate this promising method of prevention for COVID-19 and future pandemics.

Funding

No funding sources.

Competing interests

None declared.

Ethical approval

Not required.

Acknowledgement

The authors thank Dr. Harvey Risch and Peter Shabe for help with statistical analysis.

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