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.
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.
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.
References
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