Open Access Original

Article DOI: 10.7759/cureus.16897

Prophylactic Role of Ivermectin in Severe Acute

Respiratory Syndrome Coronavirus 2 Infection
Among Healthcare Workers
Priyamadhaba Behera 1 , Binod K. Patro 1 , Biswa M. Padhy 2 , Prasanta R. Mohapatra 3 , Shakti K. Bal 3 ,
Pradnya D. Chandanshive 1 , Rashmi R. Mohanty 4 , SR Ravikumar 1 , Arvind Singh 1 , Sudipta R. Singh 5 ,
Siva Santosh Kumar Pentapati 1 , Jyolsna Nair 1 , Gitanjali Batmanbane 6

1. Community Medicine and Family Medicine, All India Institute of Medical Sciences Bhubaneswar, Bhubaneswar, IND
2. Pharmacology, All India Institute of Medical Sciences Bhubaneswar, Bhubaneswar, IND 3. Pulmonary Medicine and
Critical Care, All India Institute of Medical Sciences Bhubaneswar, Bhubaneswar, IND 4. General Medicine, All India
Institute of Medical Sciences Bhubaneswar, Bhubaneswar, IND 5. Forensic Medicine, All India Institute of Medical
Sciences Bhubaneswar, Bhubaneswar, IND 6. Medicine, All India Institute of Medical Sciences Bhubaneswar,
Bhubaneswar, IND

Corresponding author: Gitanjali Batmanbane, [email protected]

Abstract
Introduction
Healthcare workers (HCWs) are vulnerable to getting infected with severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2). Preventing HCWs from getting infected is a priority to maintain healthcare
services. The therapeutic and preventive role of ivermectin in coronavirus disease 2019 (COVID-19) is being
investigated. Based on promising results of in vitro studies of oral ivermectin, this study was conducted with
the aim to demonstrate the prophylactic role of oral ivermectin in preventing SARS-CoV-2 infection among
HCWs at the All India Institute of Medical Sciences (AIIMS) Bhubaneswar.

Methods
A prospective cohort study was conducted at AIIMS Bhubaneswar, which has been providing both COVID
and non-COVID care since March 2020. All employees and students of the institute who provided written
informed consent participated in the study. The uptake of two doses of oral ivermectin (300 μg/kg/dose at a
gap of 72 hours) was considered as exposure. The primary outcome of the study was COVID-19 infection in
the following month of ivermectin consumption, diagnosed as per Government of India testing criteria (real-
time reverse transcriptase polymerase chain reaction [RT-PCR]) guidelines. The log-binomial model was used
to estimate adjusted relative risk (ARR), and the Kaplan-Meier failure plot was used to estimate the
probability of COVID-19 infection with follow-up time.

Results
Review began 07/04/2021
Of 3892 employees, 3532 (90.8%) participated in the study. The ivermectin uptake was 62.5% and 5.3% for
Review ended 07/26/2021 two doses and single dose, respectively. Participants who took ivermectin prophylaxis had a lower risk of
Published 08/05/2021 getting symptoms suggestive of SARS-CoV-2 infection (6% vs 15%). HCWs who had taken two doses of oral
© Copyright 2021
ivermectin had a significantly lower risk of contracting COVID-19 infection during the following month
Behera et al. This is an open access (ARR 0.17; 95% CI, 0.12-0.23). Females had a lower risk of contracting COVID-19 than males (ARR 0.70; 95%
article distributed under the terms of the CI, 0.52-0.93). The absolute risk reduction of SARS-CoV-2 infection was 9.7%. Only 1.8% of the participants
Creative Commons Attribution License reported adverse events, which were mild and self-limiting.
CC-BY 4.0., which permits unrestricted
use, distribution, and reproduction in any
medium, provided the original author and Conclusion
source are credited.
Two doses of oral ivermectin (300 μg/kg/dose given 72 hours apart) as chemoprophylaxis among HCWs
reduced the risk of COVID-19 infection by 83% in the following month. Safe, effective, and low-cost
chemoprophylaxis has relevance in the containment of pandemic alongside vaccine.

Categories: Preventive Medicine, Infectious Disease, Public Health

Keywords: covid-19, ivermectin, chemoprophylaxis, healthcare workers, cohort study

Introduction
The coronavirus disease 2019 (COVID-19) pandemic that started as an outbreak in Wuhan, Hubei Province
of China, in December 2019 has affected around 199 million people worldwide and caused the death of
approximately 4 million people [1]. In India, about 31 million people have been infected with this, and
425,195 people have died due to this disease [2]. Although healthcare workers (HCWs) represent less than
3% of the population in the large majority of countries and less than 2% in almost all low- and middle-
income countries, around 14% of COVID-19 cases reported to the World Health Organization (WHO) are

How to cite this article

Behera P, Patro B K, Padhy B M, et al. (August 05, 2021) Prophylactic Role of Ivermectin in Severe Acute Respiratory Syndrome Coronavirus 2
Infection Among Healthcare Workers. Cureus 13(8): e16897. DOI 10.7759/cureus.16897
 among HCWs, with the proportion reaching as high as 35% in some countries [3]. HCWs are more vulnerable
to infection due to the very nature of their occupation, and ensuring their safety is of paramount
importance in a functioning health system. Therefore, the prevention of COVID-19 disease among HCWs is
a priority for all administrators and governments.

Despite the high advocacy on behavioral prophylaxis since the start of the pandemic, cases and deaths have
not declined, indicating that only behavioral prophylaxis may not be enough to control the COVID-19
pandemic. In addition to behavioral prophylaxis, there is a need for an alternate safe intervention that can
provide protection against COVID-19. To date, there is no effective cure available to treat [4]. The beneficial
role of ivermectin in the prevention, as well as treatment of COVID-19, has been explored in the recent past
[5-8]. The well-known in vitro study by Caly et al., observational studies, and an open-label randomized
controlled trial (RCT) conducted so far have suggested the potential role of ivermectin as chemoprophylaxis
for the prevention of COVID-19 [5-8].

This article was previously posted on the Research Square preprint platform on February 15, 2021.

Materials And Methods

The aim of this study was to demonstrate the prophylactic role of oral ivermectin in preventing severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among HCWs at the All India Institute of
Medical Sciences (AIIMS), Bhubaneswar, India. A prospective cohort study was conducted at the
AIIMS Bhubaneswar during September to November 2020. All staff members of the institute formed the
study cohort, which included the clinical staff engaged in inpatient care activities, administrative staff, and
students. The protocol was approved by the Institutional Ethics Committee of AIIMS Bhubaneswar (T/IM-
NF/CM&FM/20/142). All methods were performed in accordance with the relevant guidelines and
regulations. Written informed consent was obtained from each participant. Efforts were taken to maintain
the anonymity of the participants throughout the process. Telephonic data collection was done for the
consumption of ivermectin tablets, appearance of symptoms (influenza-like illness [ILI]) and results of real-
time reverse transcriptase polymerase chain reaction (RT-PCR) testing for COVID-19. The study participants
were enrolled from September 17, 2020. They received ivermectin during September 20-30, 2020, and were
followed up after one month of taking oral ivermectin from October 20 to October 30, 2020, to assess the
outcome.

Based on a consensus statement prepared by experts from the hospital's various departments, on September
17, 2020, the prophylactic dose of oral ivermectin were made available to HCWs and students [8]. The
consensus statement recommended and approved a regimen of 300 μg/kg/dose body weight with the first
two doses taken 72 hours apart, followed by a once-monthly dose on the 30th day from the last dose.
Ivermectin was made available free of cost to the HCWs. The intake of two doses of oral ivermectin (300
μg/kg/dose in a gap of 72 hours) was considered as exposure. HCWs were provided the oral ivermectin
according to the bodyweight in the form of multiple of tablets, and dosage was similar to the doses used in
the RCT by Shouman [7]. The outcome was defined as a confirmed case of COVID-19 detected by RT-PCR.
HCWs were tested following the Government of India testing strategy for COVID-19 at the institute [9]. All
participants who had symptoms (for ILI) or had high-risk contact with an RT-PCR-confirmed COVID-19
case were tested during the follow-up. Furthermore, the HCWs were followed up through telephonic calls to
confirm their COVID-19 status after a month of distribution of ivermectin prophylaxis.

Statistical analysis was done using Stata 13.0 software (StataCorp, College Station, TX). The means and
standard deviations were reported for continuous variables and proportions for categorical variables. The
log-binomial model was used to estimate adjusted relative risk (ARR) [10]. Relative risk was adjusted for age,
gender and profession. We also performed a sensitivity analysis, excluding those who were COVID-19
positive before the ivermectin prophylaxis. The Kaplan-Meier failure plot was used to estimate the
probability of SARS-CoV-2 infection with follow-up time. COVID-19-positive HCWs and students during the
study period were treated at the institute.

Results
The institute was functioning with 3892 members during September 2020. Out of 3892, 262 were excluded
from the study as they did not consent to participate in the study. Another 98 participants could not be
followed up and were excluded from the study. A total of 3532 participants were included in the study. The
mean (SD) age was 30.6 (8.6) years. Over half of the study participants were less than 30 years of age (53.4%),
while one-third (32.3%) were in the 30- to 39-year age group. The majority of participants were male
(67.6%). Approximately three-fourths (72.7%) of the participants were involved in the direct management of
COVID-19 patients. Administrative staff and students comprised 13.9% and 13.4%, respectively. Among the
2567 participants, who were involved in COVID-19 patient care, 812 were doctors, 717 were nursing officers,
and 1038 were supporting staff.

Uptake of ivermectin was 67.5% (62.2% two doses and 5.3% single dose). Rest of the 1147 (32.5%)
participants did not consume ivermectin as prophylaxis. The symptoms suggestive of SARS-CoV-2 infection
(as per WHO guideline) were present among 331 (9.4%) participants during the one-month follow-up [11]. A

2021 Behera et al. Cureus 13(8): e16897. DOI 10.7759/cureus.16897 2 of 9

 total of 201 (5.7%) persons within our cohort tested COVID-19 positive during the one-month follow-up
period (Table 1).

Characteristic Number of participants, n (%)

Age (years)

<30 1887 (53.4)

30-39 1139 (32.3)

40-49 358 (10.1)

≥50 148 (4.2)

Gender

Male 2389 (67.6)

Female 1143 (32.4)

Profession

Staff involved in COVID-19 patient care 2567 (72.7)

Administrative staff 492 (13.9)

Students 473 (13.4)

Ivermectin prophylaxis

No ivermectin prophylaxis 1147 (32.5)

Received single-dose ivermectin prophylaxis 186 (5.3)

Received double-dose ivermectin prophylaxis 2199 (62.2)

Symptoms suggestive of SARS-CoV-2 infection during follow-up

Present 331 (9.4)

Absent 3201 (90.6)

Follow-up confirmation of COVID-19 by RT-PCR

Positive 201 (5.7)

Negative 3331 (94.3)

TABLE 1: Characteristic features of participants (n=3532)

COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2

Ivermectin prophylaxis uptake was better with increasing age and among males. Out of 331 participants,
who had symptoms suggestive of SARS-CoV-2 infection, 200 (60.4%) participants were from the group who
had not taken ivermectin prophylaxis. The participants who took ivermectin prophylaxis had a lower risk
(6% vs 15%) of getting symptoms suggestive of SARS-CoV-2 infection (Table 2).

2021 Behera et al. Cureus 13(8): e16897. DOI 10.7759/cureus.16897 3 of 9

 Ivermectin two-dose prophylaxis

Variables Yes No p-value

Age (years) <0.001

<30 1115 (50.7) 772 (57.9)

30-39 705 (32.1) 434 (32.6)

40-49 262 (11.9) 96 (7.2)

≥50 117 (5.3) 31 (2.3)

Gender <0.001

Male 1622 (67.9) 767 (32.1)

Female 577 (50.5) 566 (49.5)

Profession 0.236

Staff involved in COVID-19 patient care 1582 (71.9) 985 (73.9)

Administrative staff 306 (13.9) 186 (13.9)

Students 311 (14.2) 162 (12.2)

Symptoms suggestive of SARS-CoV-2 infection during follow-up <0.001

Positive 131 (6.0) 200 (15.0) <0.001

Negative 2068 (94.0) 1133 (85.0)

TABLE 2: Distribution of participants with ivermectin prophylaxis

COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2

The incidence of SARS-CoV-2 infection was found to be lower in the ivermectin prophylaxis group compared
to the group without ivermectin (2.0% vs 11.7%). The absolute risk reduction was 9.7%. Participants who had
taken two doses of ivermectin prophylaxis had a lower risk of contracting COVID-19 disease (RR 0.18; 95%
CI, 0.13-0.25) in the following month after receiving prophylaxis. On adjusting for age, sex, and profession,
the single dose of ivermectin intake was not significant for lowering the risk of COVID-19 disease (ARR 1.04;
95% CI, 0.69-1.58). However, two doses of ivermectin prophylaxis had a significantly lower risk (ARR 0.17;
95% CI, 0.12-0.23). Females had a lower risk (ARR 0.70; 95% CI, 0.52-0.93) of contracting COVID-19 disease
compared to males (Table 3).

2021 Behera et al. Cureus 13(8): e16897. DOI 10.7759/cureus.16897 4 of 9

 Total Follow-up (one month), Unadjusted RR p- Adjusted RR* p-
Variables
participants COVID-19 positive (95% CI) value (95% CI) value

Age (years)

<30 1887 (53.4) 116 (57.7) Reference Reference

0.87 (0.65-
30-39 1139 (32.3) 61 (30.3) 0.87 (0.64-1.18) 0.370 0.392
2.18)

0.95 (0.59-
40-49 358 (10.1) 18 (9.0) 0.82 (0.50-1.33) 0.415 0.848
1.54)

0.85 (0.39-
≥50 148 (4.2) 6 (3.0) 0.66 (0.30-1.47) 0.310 0.694
1.89)

Gender

Male 2389 (67.6) 138 (68.7) Reference Reference

0.70 (0.52-
Female 1143(32.4) 63 (31.3) 0.95 (0.71-1.27) 0.751 0.015
0.93)

Profession

Staff involved in COVID-19

2567 (72.7) 150 (74.6) Reference Reference
patient care

0.82 (0.54-
Administrative staff 492 (13.9) 24 (11.9) 0.83 (0.55-1.27) 0.399 0.354
1.24)

1.09 (0.74-
Students 473 (13.4) 27 (13.5) 0.98 (0.66-1.45) 0.908 0.652
1.61)

Ivermectin prophylaxis

No ivermectin prophylaxis 1147 (32.5) 133 (66.2) Reference Reference

Received single-dose 1.04 (0.69-

186 (5.3) 23 (11.4) 1.07 (0.70-1.61) 0.761 0.846
ivermectin prophylaxis 1.58)

Received two-dose ivermectin 0.17 (0.12-

2199 (62.2) 45 (22.4) 0.18 (0.13-0.25) <0.001 <0.001
prophylaxis 0.23)

TABLE 3: Risk factors for SARS-CoV-2 infection

*Adjusted for age, gender and profession.

RR, relative risk; COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2

We estimated the hazard ratio (HR), excluding those who had been diagnosed as COVID-19 positive before
the commencement of the study using the Kaplan-Meier method. The probability of SARS-CoV-2 infection
was 85% lower (HR 0.15; 95% CI, 0.11-0.21) in those taking two-dose ivermectin at the end of 30 days
(Figure 1).

2021 Behera et al. Cureus 13(8): e16897. DOI 10.7759/cureus.16897 5 of 9

 FIGURE 1: Probability of SARS-CoV-2 infection with ivermectin
prophylaxis
COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2

The information regarding adverse effects was collected through the existing pharmacovigilance services of
the institute, and telephonic follow-up. A total of 42 (1.8%) participants reported adverse events following
oral ivermectin. All adverse effects were self-limiting and mild in nature, and none required medication or
hospitalization. Adverse events were headache, diarrhoea, nausea, itching, rashes, fatigue, vomiting,
dizziness, and abdominal pain (Table 4).

Adverse event n (%)

Itching 5 (0.2)

Headache 9 (0.4)

Rashes 3 (0.1)

Diarrhoea 7 (0.3)

Dizziness 2 (0.1)

Nausea 7 (0.3)

Vomiting 3 (0.1)

Fatigue 4 (0.2)

Abdominal pain 2 (0.1)

Total 42 (1.8)

TABLE 4: Adverse events following ivermectin prophylaxis (n=2385)

Discussion
We noticed an increasing number of HCWs getting infected with SARS-CoV-2 infection in early September
2020 at our hospital, which was negatively impacting the healthcare services we had to provide (Figure 2).
After carefully assessing the published information on ivermectin, we decided to investigate the role of

2021 Behera et al. Cureus 13(8): e16897. DOI 10.7759/cureus.16897 6 of 9

 ivermectin prophylaxis in the prevention of COVID-19 among HCWs following one month of administration
in our hospital.

FIGURE 2: COVID-19 daily positive cases among healthcare workers

during September-October 2020
COVID-19, coronavirus disease 2019

We observed that the HCWs who took ivermectin chemoprophylaxis had an 83% lower risk of contracting
COVID-19 in the following month compared to those who did not receive the drug. Based on its long history
of clinical use, favorable safety profile, and emerging evidence from the in vitro study, observational study,
and open-label RCT, ivermectin was used as a prophylactic agent for COVID-19 infection in our hospital for
HCWs and has shown promising results. The adverse effects reported by the subjects were few and fit into
the safety profile of this drug.

Ivermectin is a widely available anti-parasitic drug and has been included in the WHO list of essential
medicines. The safety of the drug has been established by its large-scale use in the last four decades for
various indications such as onchocerciasis, scabies, head lice, and other parasitic infestations such as
ascariasis and trichuriasis [12]. Ivermectin has been reported to inhibit the interaction between importin
(IMP) α/β1 heterodimer integrase protein, which helps in the nuclear import and propagation of infection by
RNA viruses. It exerts its antiviral activity against a variety of RNA viruses, including West Nile virus,
influenza virus, and dengue virus [13]. An in vitro study by Caly et al. reported a nearly 5000-fold reduction
in the SARS-CoV-2 viral RNA with the use of ivermectin [5]. However, a simulation study has suggested that
despite a high lung:plasma concentration ratio, ivermectin would not achieve the required inhibitory
concentration in the lungs after a single oral administration at the approved dose and may necessitate much
higher doses [14]. Nevertheless, clinical studies have shown that the addition of ivermectin at doses ranging
from 150 to 200 μg/kg body weight led to lower mortality and greater clinical improvement in COVID-19
patients. A recent meta-analysis explored its therapeutic potential in COVID-19 patients and reported a
significant reduction in all-cause mortality with a pooled odds ratio of 0.53 (95% CI, 0.29-0.96, p=0.04) with
the addition of ivermectin as compared to standard therapy [15]. A recent retrospective cohort study by
Rajter et al. also demonstrated that ivermectin lowered mortality during treatment of COVID-19 [16].

A randomized open-label clinical trial carried out by Shouman in Egypt showed that prophylactic ivermectin
therapy at an average dose of 300 μg/kg body weight in primary contacts of COVID-19 patients led to
significantly lower infections (7.4%) compared to controls (58.4%) [7]. The half-life of the drug is 12-36 hours
following oral administration, and it undergoes hepatic metabolism and is eliminated primarily through the
faecal route over 12 days, with less than 1% being eliminated through the renal route. The active metabolites

2021 Behera et al. Cureus 13(8): e16897. DOI 10.7759/cureus.16897 7 of 9

 persist in the body for three days [12]. The dose regimen chosen for prophylaxis in our study was thus based
on these pharmacokinetic parameters, and the fact that dosage chosen in the clinical trial by Shouman was
associated with high clinical efficacy and low rate of adverse events [7]. In our study, we also found that
females had a lower risk of SARS-CoV-2 infection compared to males. The previous research from India also
had similar findings [17-18].

The strengths of our study are the large sample size, minimal loss to follow-up, and the establishment of
temporality. The ideal study design to answer our research question would be a randomized controlled
clinical trial. However, due to ethical reasons, we could not choose this design. HCWs who took ivermectin
may somehow differ from the HCWs who did not prefer to take the prophylaxis in their behaviour. However,
we had a strong institutional policy in place related to COVID-19-appropriate behavior in the workplace,
which may have avoided the possible bias. The major limitation is that we only tested HCWs who either
developed symptoms or who were direct or high-risk contacts of positive patients. This was done in keeping
with the Government strategy for COVID-19 testing in India. However, this precludes us from including the
HCWs who may have been asymptomatic or mildly symptomatic and chose not to get tested.

We believe that ivermectin is a low-cost prophylaxis (one 12-mg tablet cost us 8 INR/0.1 USD) that can
easily be used in many settings to reduce the burden of the disease. Further research is required to guide the
frequency of chemoprevention, acceptability, and cost-effectiveness in the community setting.

Conclusions
Two doses (300 μg/kg/dose in a gap of 72 hours) of ivermectin chemoprophylaxis reduced COVID-19
infection by 83% among HCWs for one month. Ivermectin is a safe and effective strategy to prevent COVID-
19, in the containment of pandemic alongside vaccine. Further research is required to guide the frequency of
chemoprevention, acceptability, and cost-effectiveness in the community setting.

Additional Information
Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics
Committee of AIIMS Bhubaneswar issued approval T/IM-NF/CM&FM/20/142. The study was conducted
according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Ethics
Committee of AIIMS Bhubaneswar. Animal subjects: All authors have confirmed that this study did not
involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure
form, all authors declare the following: Payment/services info: All authors have declared that no financial
support was received from any organization for the submitted work. Financial relationships: All authors
have declared that they have no financial relationships at present or within the previous three years with
any organizations that might have an interest in the submitted work. Other relationships: All authors have
declared that there are no other relationships or activities that could appear to have influenced the
submitted work.

Acknowledgements
We are grateful to Prof. Sonu H Subba, MD, for her administrative support during the study. We are thankful
to all participants for their willingness and support in the study.

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