Role of ivermectin in the prevention of SARS-CoV-2 infection among healthcare workers in India: A matched case-control study
Ivermectin is one among several potential drugs explored for its therapeutic and preventive role in SARS-CoV-2 infection. The study was aimed to explore the association between ivermectin prophylaxis and the development of SARS-CoV-2 infection among healthcare workers.
A hospital-based matched case-control study was conducted among healthcare workers of AIIMS Bhubaneswar, India, from September to October 2020. Profession, gender, age, and date of diagnosis were matched for 186 case-control pairs. Cases and controls were healthcare workers who tested positive and negative, respectively, for COVID-19 by RT-PCR. Exposure was defined as the intake of ivermectin and/or hydroxychloroquine and/or vitamin C and/or other prophylaxis for COVID-19. Data collection and entry were done in Epicollect5, and analysis was performed using STATA version 13. Conditional logistic regression models were used to describe the associated factors for SARS-CoV-2 infection.
Ivermectin prophylaxis was taken by 76 controls and 41 cases. Two-dose ivermectin prophylaxis (AOR 0.27, 95% CI, 0.15–0.51) was associated with a 73% reduction of SARS-CoV-2 infection among healthcare workers for the following month. Those involved in physical activity (AOR 3.06 95% CI, 1.18–7.93) for more than an hour/day were more likely to contract SARS-CoV-2 infection. Type of household, COVID duty, single-dose ivermectin prophylaxis, vitamin-C prophylaxis, and hydroxychloroquine prophylaxis was not associated with SARS-CoV-2 infection.
Two-dose ivermectin prophylaxis at a dose of 300 μg/kg with a gap of 72 hours was associated with a 73% reduction of SARS-CoV-2 infection among healthcare workers for the following month. Chemoprophylaxis has relevance in the containment of pandemics.
The SARS-CoV-2pandemic has claimed over 2,041,426 lives and affected over 95,567,167 persons worldwide by 18th January 2021. Meanwhile, the subcontinent of India has reported 10,572,672 active coronavirus disease 2019 (COVID-19) confirmed cases and 152,458 deaths related to the same virus ]. The respiratory system is commonly involved in COVID-19, causing fever, cough, and dyspnoea . Alteration of the smell and taste, gastrointestinal symptoms, headache, and cutaneous manifestations are other associated symptoms that have been reported with COVID-19 ].
Worldwide, healthcare workers (HCW) working on the frontline are at risk of exposure to the virus as they battle to save patients with COVID-19. A systematic review on infection and deaths in HCWs due to COVID-19 found that the number of infected HCWs workers ranged from 1,716 to 17,306, varying from country to country . Another report in September 2020 stated that COVID-19 had infected nearly 570,000 HCWs while as many as 2,500 had succumbed to the disease in the region of the Americas . Organizations at international and national levels have shared advisories and guidelines with measures to ensure the safety of HCWs while they serve amidst the COVID-19 pandemic. Provision of Personal Protective Equipment (PPE) while on duty, free-of-cost SARS-CoV-2 testing, timely payments, support helplines, online discussions, training, and capacity building for infection prevention and control are some of the measures taken to prevent the infection and spread of COVID-19 among HCWs .
Materials and methods
The present study is a hospital-based matched case-control study conducted among HCWs of the All India Institute of Medical Sciences (AIIMS) in Bhubaneswar, Odisha, India, during September-October 2020. To calculate sample size, we assumed ivermectin prophylaxis in the control group to be 22% as there were no data available from prior studies. Considering, 80% power, 5% alpha, 1:1 matching of cases to controls, minimum discordant pairs to be detected was set to 54, with an expected odds ratio of 0.5, the sample size was estimated to be 186 pairs, i.e., 372 individuals . Cases and controls were identified from the existing line list, which was prepared by the contact tracing team at AIIMS Bhubaneswar. The line list contained the list of the AIIMS Bhubaneswar HCWs’ risk of exposure to SARS-CoV-2based on the assessment carried out using the WHO risk assessment guidelines]. This risk assessment helped in identifying the population of cases and controls having similar risks. Cases were HCWs who were diagnosed as positive for COVID-19 by Reverse Transcription Polymerase Chain Reaction (RT-PCR). Controls were defined as HCWs who were diagnosed as negative for COVID-19 by RT-PCR with a similar risk of exposure towards-CoV-2. For every enrolled case, a control was selected from the existing line list. Individual matching was carried out for profession, gender, and age. In addition, an attempt was made to match the date of diagnosis. However, when the match was not possible for the same date, the control was selected from the nearest possible date of diagnosis. In the majority of cases, it was within a week. The average number of days for a difference in date of diagnosis was 3.8 days between cases and controls. Exposure was defined as the prophylaxis viz., ivermectin and/or (HCQ) and/or vitamin C and/or other agent took for the prevention of COVID-19. The HCWs of AIIMS Bhubaneswar were advised to take HCQ prophylaxis as per Indian Council of Medical Research (ICMR) guidelines from 11th April 2020 [, in addition to using appropriate PPE depending on the place they were posted. However, the uptake was not encouraging on account of known cardiovascular adverse effects of HCQ. Further, on 17th September 2020, a decision to provide all HCWs with ivermectin for prophylactic use was announced, based on a consensus statement that was released at the institute ().
A total of 904 individuals working in AIIMS, Bhubaneswar, got tested for SARS-CoV-2 during one month (20th September 2020-19th October 2020). Out of 904 persons who were tested, 234 persons tested positive, and 670 persons tested negative for COVID-19. After matching with the profession, gender, age, and date of diagnosis, there were 190 cases for which controls were available. Out of 190 cases, four did not give consent for participation. Therefore,186 matched pairs or 372 participants were finally included in our study. Participants had a mean (SD) age of 29± 6.83 years, and the mean difference in date of diagnosis between cases and control was 3.8 days. In one matched case-control pair, one intern was matched with a final year undergraduate student, which was the closest possible match for the case. The profession of the remaining 185 case-control pairs was perfectly matched. Out of 186 cases, 18 (9.7%) cases were admitted to a hospital, while 168 (91.3%) cases opted for home isolation.
Credited to PLoS one