Can Hydroxychloroquine Prophylaxis be Useful among Health Care Workers in Prevention of COVID-19?

Received: 23-Feb-2021 Accepted Date: Mar 23, 2021 ; Published: 30-Mar-2021

Introduction

Health Care Workers (HCW) are at significant risk for disease transmission while fighting COVID-19. A considerable number of HCW have been infected with SARS COV-2 worldwide, and some had, unfortunately, lost their lives. In the People’s Republic of China, as of February 24, 2020, 3387 of 77.262 patients infected with COVID-19 were reported to be HCW involved in the management of COVID-19 patients [1]. In Italy, in March 2020, 20% of HCW who took part in managing COVID-19 patients became infected, and several of them died [2]. These events justified the search for extra measures in addition to using personal protective equipment and isolation precautions to protect HCW before developing the disease. In-vitro studies demonstrated the inhibitory effect of hydroxychloroquine on virus entry to the cell [3,4]. Therefore, repurposing hydroxychloroquine to use in prophylaxis is of interest.

A recent study proposed the use of hydroxychloroquine in prophylaxis for COVID-19 [5]. Zhou, et al. also suggested that hydroxychloroquine may be useful in preventing the development of disease [6]. Many HCW obtained hydroxychloroquine before and after exposure without valid clinical evidence.

Except for one comparative study among healthcare professionals evaluating the efficacy of hydroxychloroquine in pre-exposure prophylaxis many of them have not been published so far [7-9]. In this study, we aimed to evaluate the effectiveness of hydroxychloroquine in pre-exposure and post-exposure prophylaxis on the prevention of COVID-19 among HCWs.

Methods

Setting and Data Collection

We conducted a single-center retrospective cohort study in an affiliated tertiary care hospital. We obtained ethical approval from the Institute Ethics Committee, and signed informed consent was waived (2020/0320). The procedures followed were as per the ethical standards of the responsible committee on human experimentation (institutional or regional) and with the Helsinki Declaration (1964, amended most recently in 2008) of the World Medical Association.

This study was conducted between March 20 and June 20 of 2020. During the study period, the participating HCW had been informed about the use of masks in their social lives, compliance with the social distance rule, and avoiding crowded areas, and encouraged to be in line with preventive measures. We applied pre-exposure prophylaxis to HCWs according to their self-decision and willingness with hydroxychloroquine 200 mg PO weekly in consecutive weeks during the study period. Post-exposure prophylaxis was initiated with hydroxychloroquine, given 200 mg twice daily orally for three consecutive days to HCW after exposure in the hospital or social area in the first 96 hours of exposure to a SARS-CoV-2 PCR positive patient, as per the recommendations of the Ministry of Health of Turkey in April 2020 [10]. High-risk exposure was defined as exposure to a COVID-19 patient without protective equipment. Medium-risk exposure was defined as exposure using protective equipment inappropriately, while low-risk exposure was defined as exposure using personal protective equipment properly. Personal protective equipment was a surgical mask (or N95 respirator), protective eyeglasses, and disposable protective clothing. We defined the appropriate use of protective equipment as wearing a medical mask, respirator (in the presence of aerosol-generating procedures), glasses, and disposable clothing before exposure and disposing of all protective equipment followed by hand hygiene immediately after exposure. We followed the HCWs, who had a risky exposure history, with active symptom monitoring. We performed a PCR test on the symptom day if symptoms developed, and on the 7th day if not.

The primary outcome for the pre-exposure prophylaxis group was symptomatic or asymptomatic COVID-19 infection confirmed by PCR during the study period. The primary outcome for the post-exposure prophylaxis group was symptomatic or asymptomatic COVID-19 infection confirmed by PCR within 5 to 14 days from exposure. PCR test was performed immediately at the onset of COVID-19 symptoms or whenever an HCW requested for a PCR test.

At the end of the study period, we conducted an online structured survey. We contacted participants where necessary to resolve conflicts among survey responses. Medical records of the hospital also validated the data.

Statistical Analysis

For statistical comparisons, we used the open-source platform R (Vienna, Austria). Variables that violate the normality assumption were presented as the median and Interquartile Range (IQR). We applied the Student’s t-test or the Wilcoxon rank-sum test to analyze continuous variables and the Chi-square test or Fisher’s exact test to analyze categorical variables where required.

We constrıcted logistic models using the “RMS” package. We fit the final logistic model using potentially confounding variables. We tested collinearity and interactions between predictors and presented estimates of marginal effects.

Results

A total of 492 HCW who worked in our hospital were recruited for the study. Table 1 presents the characteristics of the study cohort. Briefly, the median (IQR) age of participants was 30 (26, 38) years, and the frequency of female gender was 64% (314). A total of 213 (43%) participants were nurses, midwives, and health technicians, and 133 (27%) were resident doctors. A total of 456 participants had a risky exposure history; 420 (92.1%) had contact in the hospital, 36 (7.9%) had contact outside the hospital (family or social exposure). 46 of 456 participants reported more than one risky exposure. Among the participants, 8.1% (40/492) and 31% (152/492) obtained pre and post-exposure prophylaxis. A total of 47 (9.6%) patients had at least one positive PCR test.

Table 1 Characteristics of the cohort

Table 2 displays univariate comparisons of factors according to the PCR status of participants. Briefly, age and gender were not different, while prophylaxis status and occupation had some variations. Residents and hospital cleaners were the most frequently infected HCWs, while participants who had medium and high-risk exposures were most commonly infected.

Table 2 Characteristics of patients according to PCR results

Table 3 displays the frequency of prophylaxis types according to exposure risk rating. Most patients declared that they had a medium risk exposure. The final logistic model displayed an inverse association between post-exposure prophylaxis and COVID-19 infection (effect-1.179; 95% limits, (-1.969; -0.390)) (Table 4).

Except for transient palpitations, none of the participants had severe side effects due to hydroxychloroquine utilization.

Table 3 The frequency of prophylaxis types among exposure risk rating

Table 4 Effect estimates from the final logistic model

Discussion

We found that hydroxychloroquine post-exposure prophylaxis had an inverse association with COVID-19 infection among HCWs. On the other hand, the hydroxychloroquine pre-exposure prophylaxis had no association with the outcome. A recently published randomized, double-blind, placebo-controlled clinical trial also reported that there was no clinical benefit of hydroxychloroquine administered daily for 8 weeks as pre-exposure prophylaxis in hospitalbased HCWs exposed to patients with COVID-19 [11].

A recently published randomized controlled, double-blind study found no significant difference in post-exposure prophylaxis between participants receiving hydroxychloroquine compared to those receiving placebo. Side effects were more common in the hydroxychloroquine arm [12]. A study from South Korea reported no PCR positivity in HCWs who had potential exposure to the index case. These patients instituted 400 mg/day hydroxychloroquine prophylaxis within 58 hours of exposure and were used for 14 days. However, in this study, there was no control group, and only nine HCWs were considered high-risk exposure [13]. In a recent retrospective study conducted in Italy, patients who were in hydroxychloroquine drug regimens due to chronic dermatologic or rheumatologic diseases were phone interviewed. Among these patients, none had SARS-CoV-2 infection-related symptoms in the last two months. However, the main limitation of the study by Lee SH et al was the absence of exposure to COVID-19 cases [14]. Other randomized controlled clinical trials evaluating the effectiveness of post-exposure prophylaxis in adults have not yet been concluded [15]. In our study, post-exposure prophylaxis was associated with a favorable outcome.

Conclusion and Limitations

Interestingly, we found that PCR-proven COVID-19 infection was higher among those who received pre-exposure prophylaxis than all other groups, including those who did not receive any prophylaxis. It is also possible that the prophylactic use of hydroxychloroquine may create false confidence, and so may cause HCW to neglect personal protective measures.

The limitation of our study is that it is a single-center study, and participating groups were not randomized. Although the data were confirmed by the hospital automation system and by phone call when necessary, the data were collected through an online questionnaire. On the other hand, the inclusion of only the volunteers in the study causes selection bias.

We have observed in our hospital that hydroxychloroquine is not effective in preventing disease in pre-exposure prophylaxis. On the other hand, post-exposure prophylaxis was associated with decreased PCR-confirmed COVID-19 cases among HCW. However, to make strong inferences, more studies should be undertaken.

Declarations

Conflicts of Interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Fundings

The authors received no specific funding for this work.

References

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