Prophylactic use of hydroxychloroquine (HCQS) in COVID-19: A questionnaire-based study in health care professionals.

Background: Coronavirus disease-2019 (COVID-19) pandemic has engulfed the whole world with millions getting infected and losing their lives. Health care professionals (HCPs) who are in the front line of fighting with COVID-19 are particularly vulnerable and it is crucial to protect them from COVID-19. In this regard, the Indian Council of Medical Research (ICMR) has recommended hydroxychloroquine (HCQS) chemoprophylaxis in HCPs. However, considering the lack of sufficient evidence the HCP are in a dilemma about this aspect. Moreover, there is a paucity of data on use of HCQS as a chemoprophylaxis among Indian HCP. Hence, this study was carried out to study the extent of use and also the perception of Indian HCP toward use of HCQS as a chemoprophylaxis for COVID-19. Materials and
Methods: This was a cross-sectional study done on 205 HCPs working across India. The responses were collected electronically using a prevalidated semi-structured questionnaire.
Results: 62.9% (129/205) respondents reported having taken HCQS chemo-prophylaxis for COVID-19 while 34.7% (76/205) did not take it. Among HCP, who did not take the prophylaxis, the main reasons cited were concern about adverse effects (61.5%) and lack of robust evidence (24%). Only 14% of respondents felt that there was sufficient evidence to justify use of HCQS for prophylaxis while an overwhelming majority (86%) felt otherwise or were uncertain.
Conclusion: The majority of participants felt that despite a lack of proven efficacy, ICMR guidelines on HCQS prophylaxis in COVID-19 are justified considering the pandemic situation. Our study also found that HCQS is well tolerated by participants and there was no reported serious adverse effect and cardiac-related side effects among them.

INTRODUCTION

Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an international public health emergency. About 15% of the cases of COVID-19 suffer from severe form of disease and 6% being fatal.[12] The first case of COVID-19 was diagnosed in December 2019 in Wuhan province of China.[3] The infection spread very rapidly within a short span of time throughout the world and became a pandemic.[4] India had shown a staggered course of SARS-CoV-2 transmission initially. However, there has been a surge in cases with 7,597,063 confirmed cases of coronavirus disease with 115,197 deaths as of October 20, 2020. India stands at the number 2 among all countries in total number of cases, next only to the USA.[5]

Health care professionals (HCPs) are in the front line fighting this pandemic and in many parts of the world, they have been infected by SARS-CoV-2 during the course of their work leading to many of them to lose their lives. This creates an extra burden on the already stretched human health resource and it is imperative that adequate steps including due personal protective measures are provided to protect these health workers.

As of now, there is no effective, proven, pharmacological treatment for this viral disease. In the absence of any known therapy and because of the situation of a “public-health emergency,” many drugs have been tried in the treatment for COVID-19 with limited results.[6]

Hydroxychloroquine (HCQS) has emerged as a drug which may have some effect on the viral multiplication of SARS-CoV-2. It is also postulated that HCQS impairs the terminal glycosylation of the angiotensin-converting-enzyme 2 receptor, where envelope spike glycoprotein of corona virus binds, leading to reduced entry of the virus inside the host cells.[7] There have been a few in vitro studies that have suggested that HCQS which is an imunomodulator is effective in reducing viral replication in other infections, including the SARS-associated CoV and Middle East respiratory syndrome-CoV.[891011]

The Indian Council of Medical Research (ICMR), under the Ministry of Health and Family Welfare, has recommended chemoprophylaxis with HCQS (400 mg twice on day 1, then 400 mg once a week thereafter) for healthcare workers treating patients with suspected or confirmed COVID-19, and for asymptomatic household contacts of confirmed cases.[12]

Although there is some in vitro evidence that supports the antiviral activity of HCQS as mentioned above, there are no randomized trials that have evaluated HCQS prophylaxis for SARS-CoV-2 infection and no data that can show clinical improvement.[13]

Because of scarcity of evidence, there are conflicting views among health care workers including doctors and nurses who are in dilemma about the use of HCQS as a chemoprophylaxis for COVID-19. Moreover, there is no available data about the perception of Indian health care workers toward HCQS as a chemoprophylaxis for COVID-19.

Hence, this study was carried out to study the awareness and perception of Indian HCPs toward HCQS as a chemoprophylaxis for COVID-19 as recommended by ICMR. The findings of the study will greatly help to measure the extent of use of HCQS and the perceptions of health care workers for the prophylaxis of COVID-19.

MATERIALS AND METHODS

This was a cross-sectional study done on HCPs including doctors and nurses working throughout India. A prevalidated semi-structured questionnaire was prepared in English language by using Google form. The Google form consisted of two sections, the first section for study information and electronic consent form and second section consisted of the actual questionnaire. A snowball sampling technique was used to capture responses wherein the link of the questionnaire was sent to HCPs working in India through digital/electronic platform like E-mail, WhatsApp. They were encouraged to circulate this questionnaire among their colleagues. The responses were anonymous and totally secure. The data was collected over a period of 15 days. A total of 205 responses were received from HCPs from across various states of India.

Statistical analysis

The data were compiled using and analyzed using IBM SPSS V23 (IBM Corp. Released 2015. IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp). Descriptive statistics represented with Percentage.

Ethical approval

The Ethical approval was obtained from the Institutional Ethics Committee for conducting this study.

RESULTS

Table 1 shows a total of 205 respondents participated in this study. Out of 205 respondents, most of the subjects were male 128 (62.4%), 107 (52.2%) subjects were in the age group of 30–40 years. A majority of the respondents 125/205 (61%) were clinical doctors and 174/205 (84.9%) respondents had more than 5 years of professional experience.

Table 1

Profile of the health care professionals (n=205)

Personal profile	Number of responses (%)
Age (years)
≤29	28 (13.7)
30-39	107 (52.2)
40-49	38 (18.5)
50-59	26 (12.7)
≥60	6 (2.9)
Mean age (SD)	37.69 (9.74)
Gender
Male	128 (62.4)
Female	77 (37.6)
Specialization
Para clinical/preclinical doctor	55 (26.8)
Clinical doctor	125 (61.0)
Nursing professional	25 (12.2)
Professional experience (years)
≤5	31 (15.1)
6-10	89 (43.4)
11-20	43 (21.0)
≥21	42 (20.5)

SD=Standard deviation

The majority of respondents were from Maharashtra (38%), while Delhi (18%), Rajasthan (17.6%), Andhra Pradesh (8.4%), and other states (12%) [Figure 1].

Figure 1

Distribution of respondents by state (n = 205)

More than half of study subjects 118/205 (58%) were involved in COVID-19 patient care at various level [Figure 2].

Figure 2

Percentage of respondents involved in COVID care (n = 205)

Out of 205 respondents, 34 (16.5%) subjects were suffering from one or more co-morbidities, hypertension (10.7%) and diabetes (4.4%) being the most common. On the question of awareness about the advisory of ICMR, an overwhelming number 199 out of 205 (97%) were aware that HCQS is recommended by ICMR for chemo-prophylaxis of COVID-19 in HCPs.

Majority of the respondents (40%) reported social media sites/WhatsApp to be their main source of information while for 33% it was the ministry of health and family welfare website. 18% received information from multiple sources while 9% reported newspaper to be their main source of information.

More than half of the subjects 120 (58.5%) searched the literature on the use of HCQS as prophylaxis for COVID-19 [Table 2].

Table 2

Time spent in searching the literature on hydroxychloroquine sulfate (n=120)

Time (min)	Frequency (%)
≤29	41 (34.2)
30-120	54 (45)
≥121	25 (20.8)

When asked whether sufficient evidence exists to justify the use of HCQS prophylaxis of COVID-19 to respondents, 111 (54.2%) subjects answered No, while 65 (31.7%) were not sure and only about 29 (14.1%) were convinced of the evidence.

62.9% (129) of the total respondents had used HCQS chemoprophylaxis for COVID-19 while 37.1% respondent did not take HCQS chemoprophylaxis [Figure 3].

Figure 3

Respondents taking HCQS chemoprophylaxis for COVID-19 (n = 205)

Out of 129 who had taken HCQS as prophylaxis, 76 (59%) made the arrangements for the drug by themselves while 53 (41%) responded that their institute had organized the drug centrally for them. For the respondents who did not take HCQS, the reasons cited for not taking HCQs chemoprophylaxis were HCQS was not available 11 (14.5%), 47 (61.5%) worried about adverse effects and 18 (24%) responded that there was no evidence to suggest HCQS is effective [Table 3].

Table 3

Use of hydroxychloroquine sulfate chemo-prophylaxis among respondents

Total respondents	n=205, n (%)	Remarks
Patient who took HCQS	129 (63)	Made arrangement themselves - 76
		Drug arranged by institute - 53
Patient did not take HCQS	76 (37)	Reason  Fear of adverse effect - 47 There was no evidence to suggest HCQS is effective - 18 HCQS was not available - 11

HCQS=Hydroxychloroquine sulfate

Among those who took HCQS <5% respondents encountered side effects such as gastritis, epigastric discomfort, sore throat, myalgia, headache with half of these subjects’ required intervention in the form of OPD treatment.

On the question of HCQS prophylaxis by HCPs giving a false sense of security and encouraging the general population to self-medicate on HCQS, the respondents were divided. Further, 2/3rd of the respondents were in favor of electrocardiography (ECG) recording before starting HCQS. More than half of the respondents believed that HCQS does not cause serious adverse effects in a normal healthy individual. Majority of the respondents agreed that HCQS would be effective as chemoprophylaxis in COVID-19 and supported wide spread use of HCQS in a community for chemoprophylaxis. Majority of respondents are agreed that there is a possibility of shortage of HCQS for patients with lupus and Rheumatoid Arthritis (RA) if its supply is diverted for chemoprophylaxis [Figure 4].

Figure 4

Perception of respondents regarding HCQs prophylaxis (n = 205)

More than 60% of respondents felt that the ICMR guidelines on the use of HCQS for chemoprophylaxis are justified considering the overall pandemic situation [Figure 5].

Figure 5

Perception of study subjects towards Indian Council of Medical Research guidelines (n = 205)

DISCUSSION

In an effort to protect the front-line HCPs, ICMR issued an advisory recommending use of HCQS for chemo-prophylaxis against COVID-19. The advisory is significant considering that there is no clear-cut evidence showing efficacy of HCQS in treatment of COVID-19 with the jury still out on this.[1415] Because of conflicting data on HCQS usage it is still not clear to the extent of compliance of these ICMR guidelines regarding HCQS prophylaxis among HCPs. To our knowledge, there are no published studies that have investigated the extent of usage of HCQS as prophylaxis and also the perceptions of health care workers towards this aspect.

A majority of the respondents were aware about ICMR guidelines on HCQS prophylaxis. This is not surprising considering that ICMR is a premier national agency spearheading the fight against COVID-19 and HCPs closely follow its recommendations. Further, our study highlighted that even though most of the respondents acknowledged that there is no evidence suggesting the efficacy of HCQS as a prophylactic in COVID-19, they had taken HCQS as recommended by ICMR. This could be because of nonavailability of any other proven treatment and the HCPs felt that the risk-benefit ratio is not adverse in case of HCQS being taken for chemo-prophylaxis. However, around 34.7% respondents did not take HCQS prophylaxis because of fear of HCQS related adverse effects, and because of lack of evidence of HCQS as a prophylactic agent in COVID-19.

Importantly, this study also showed the occurrence of adverse effects to be low (4.7%), with GI discomfort and gastritis being the most common which are known adverse effects of HCQS.[16] There was no reported cardiac adverse effect due to HCQS among the respondents. Overall, our study shows that HCQS was well tolerated by respondents. A large percentage of respondents were in favor of ECG to be done before HCQS prophylaxis. Even though the ICMR guidelines mention that cardiac adverse effects can occur due to HCQS, there is no mandatory ECG required as per the guidelines. This aspect is noteworthy and considering that ECG is a widely available noninvasive investigation, there could be a case for mandatory ECG before HCQS prophylaxis. Majority of the respondents agreed that there will be a shortage of HCQS for patients of autoimmune disorders like RA and SLE which may lead to a flare up of these disorders. On the question of HCQS prophylaxis by HCPs giving a false sense of security and encouraging the general population to self-medicate on HCQS, the respondents were divided. Finally, our study highlighted that even though there is no published literature available, majority of respondents (64.9%) had justified the ICMR guidelines on HCQS prophylaxis for COVID-19 in health care workers. This is further highlighted by the fact that 62.9% took HCQS even though only 14% of respondents felt that there was sufficient evidence to justify use of HCQS for prophylaxis. This could be because of the fact there is no other proven drug for prophylaxis and treatment for COVID-19 till date. In such a situation, the use of HCQS, which has been widely used for a long time, presents a window of opportunity to try and protect the HCPs, and as such its use in chemo-prophylaxis may be justified.

CONCLUSION

About two-thirds of the respondents in this study took HCQS for chemo-prophylaxis of COVID-19. Further, although there is no published literature available on the efficacy of HCQS chemoprophylaxis in COVID-19, majority of respondents felt that the ICMR guidelines on HCQS prophylaxis in COVID-19 are justified. This study also found that HCQS is well tolerated and there was no reported serious adverse effect and cardiac related side effects among them.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.