Outcome of ivermectin treated mild to moderate COVID-19 cases: a single-centre, open-label, randomised controlled study

Abstract

Background and objectives: Various existing non-antiviral drugs are being used to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection based mostly on existing data from previous coronavirus outbreaks. Ivermectin is one of such agents being widely used to treat early-stage of COVID-19. This study evaluated the outcome of ivermectin treated mild to moderate COVID-19 cases compared to usual care.
Methods: This open-label randomised controlled study was conducted at a sub-district (Upazila) health complex from 1st May 2020 to the end of July 2020. Consecutive RT-PCR positive eligible COVID-19 patients were randomised into control and intervention arms. In the intervention arm, ivermectin 200 micrograms/kg single dose was administered orally in addition to usual care and was followed up till recovery. Repeat RT-PCR was done on day ten since the first positive result. The end point with regard to treatment outcome was time required for the resolution of symptoms from the onset of the symptoms and following enrollement in the study.
Results: A total of 62 mild to moderate COVID-19 patients were enrolled in the study. There were 30 patients in the control arm and 32 patients in the intervention arm. Total recovery time from the onset of symptoms to complete resolution of symptoms of the patients in the intervention arm was 10.09 ± 3.236 days, compared to 11.50 ± 5.32 days in the control arm (95% CI -0.860,3.627, p>. 05) and was not significantly different. The mean recovery time after enrolment in the intervention arm was 5.31 ± 2.48 days, which also did not differ significantly from the control arm of 6.33 ± 4.23 days (95% CI – 0.766, 2.808, p> 0.05). Results of negative repeat RT- PCR were not significantly different between control and intervention arms (control 90% vs intervention 95%, p>.05).
Conclusion: Ivermectin had no beneficial effect on the disease course over usual care in mild to moderate COVID-19 cases.

Full text

Outcome of ivermectin treated mild to moderate COVID-19 cases:
a single-centre, open-label, randomised controlled study
Chinmay Saha Podder1, Nandini Chowdhury1, Mohim Ibne Sina1, Wasim Md Mohosin Ul Haque2*
1Debidwar Upazila Health Complex, Debidwar, Comilla, Bangladesh; 2Department of Nephrology, BIRDEM
General Hospital, Dhaka, Bangladesh
Abstract
Background and objectives: Various existing non-antiviral drugs are being used to treat severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection based mostly on existing data
from previous coronavirus outbreaks. Ivermectin is one of such agents being widely used to
treat early-stage of COVID-19. This study evaluated the outcome of ivermectin treated mild to
moderate COVID-19 cases compared to usual care.
Methods: This open-label randomised controlled study was conducted at a sub-district (Upazila)
health complex from 1st May 2020 to the end of July 2020. Consecutive RT-PCR positive eligible
COVID-19 patients were randomised into control and intervention arms. In the intervention
arm, ivermectin 200 micrograms/kg single dose was administered orally in addition to usual
care and was followed up till recovery. Repeat RT-PCR was done on day ten since the first
positive result. The end point with regard to treatment outcome was time required for the
resolution of symptoms from the onset of the symptoms and following enrollement in the
study.
Results: A total of 62 mild to moderate COVID-19 patients were enrolled in the study. There
were 30 patients in the control arm and 32 patients in the intervention arm. Total recovery time
from the onset of symptoms to complete resolution of symptoms of the patients in the
intervention arm was 10.09 ± 3.236 days, compared to 11.50 ± 5.32 days in the control arm
(95% CI -0.860,3.627, p>. 05) and was not significantly different. The mean recovery time after
enrolment in the intervention arm was 5.31 ± 2.48 days, which also did not differ significantly
from the control arm of 6.33 ± 4.23 days (95% CI – 0.766, 2.808, p> 0.05). Results of negative
repeat RT- PCR were not significantly different between control and intervention arms (control
90% vs intervention 95%, p>.05).
Conclusion: Ivermectin had no beneficial effect on the disease course over usual care in mild to
moderate COVID-19 cases.
IMC J Med Sci 2020; 14(2): 002. EPub date: 03 September 2020
Introduction
Coronavirus disease (COVID-19) is caused by severe
acute respiratory syndrome coronavirus 2 (SARS-
CoV-2), which was first identified during an
outbreak of a respiratory illness in Wuhan City,
Hubei Province, China, in December 2019 [1]. On
March 11, WHO declared COVID-19 a global
pandemic [2]. To date (August 11, 2020),
approximately 20 million people worldwide have
been infected, and about 0.75 million patients died
of COVID-19. Currently, no drug is clearly found
effective in the treatment of COVID-19. Based on
experience from previous coronavirus outbreak,
some antiviral agents namely remdesivir and
*Correspondence: Wasim Md Mohosin Ul Haque, Department of Nephrology, BIRDEM General Hospital, 122 Kazi
Nazrul Islam Avenue, Dhaka 1000, Bangladesh. Email: wmmhaque@live.com
OPEN ACCESS Original Article

favipiravir, have shown some promise in the
treatment of COVID-19. However, these are very
expensive and are reserved for severe cases only
[3,4]. Treatment for patients with mild to moderate
disease is not well established [5,6]. Several
national and international observational studies
have reported encouraging results of ivermectin in
the treatment of COVID-19 patients with a mild
degree of severity [7].
Ivermectin has been a popular anti-parasitic drug
since the late 1970s. This drug stimulates gamma-
aminobutyric acid-controlled chloride channels,
which leads to hyperpolarisation and paralysis of
the affected organism. The antiviral function of
ivermectin has been discovered in recent years and
is fascinating. This drug has a wide range of
antiviral activities, both in vivo and in vitro, against
various RNA and DNA viruses [8,9]. Efficacy against
specific flaviviruses (dengue, Japanese encephalitis,
and tick-borne encephalitis virus) and the
chikungunya virus have been demonstrated in-vitro
[10,11]. In a study by Caly et al has demonstrated
that Vero/hSLAM cells infected with SARS-CoV-2
when treated with ivermectin resulted in a 5,000-
fold reduction in viral RNA after 48 hours [12]. The
exact mechanism of this effect is not yet known.
However, the possible mechanism is inhibition of
importin α / β1 mediated transport of viral proteins
in and out of the nucleus [13].
The promising result of the in-vitro study mentioned
above has led clinicians in many countries to use
ivermectin to treat COVID-19 patients. A
retrospective cohort study in hospitalised patients
with confirmed SARS-CoV-2 infection in four
hospitals in Florida showed significantly lower
mortality rates among those who received
ivermectin compared to the usual treatment [14].
The mortality rate was also significantly lower in
ivermectin-treated patients with severe lung
disease, although the rate of successful extubation
was not significantly different [14]. In an
observational study in Bangladesh, involving 100
COVID-19 patients treated with a combination of
ivermectin and doxycycline showed adequate viral
clearance in mild and moderately ill patients [7]. A
recently published randomised controlled trial in
Bangladesh found that a combination of ivermectin
and doxycycline was safe and effective in patients
infected with SARS-CoV-2, and showed no
significant adverse events and had an improved
tolerance compared to a combination of
'hydroxychloroquine and azithromycin [15].
However, there was no control (usual care) group
in this study. The available pharmacokinetic data
suggest that plasma concentrations of ivermectin
with significant activity against SARS-CoV-2 could
not be achieved without potentially toxic doses of
ivermectin in humans [13].
Therefore, use of ivermectin warrants rapid
implementation of controlled clinical trials to
assess the efficacy against SARS-CoV-2 [16].
Although observational data suggest a beneficial
effect of ivermectin in the treatment of COVID-19,
there has been no randomised controlled trial
(RCT) with ivermectin compared to the usual care
in patients with mild to moderate COVID-19.
Therefore, it is essential to conduct a clinical trial
with ivermectin in patients with COVID-19 to
evaluate the effectiveness of this drug in treating
mild to moderate COVID-19 patients. This study
was designed to evaluate the benefit of, if any,
adding ivermectin to usual care, compared to usual
care alone in the treatment of COVID-19 cases at a
semi-rural settings.
Methods
Study design, randomisation and intervention
This study was an intention to treat prospective
randomised controlled trial conducted at Debidwar
Upazila (sub-district) Health Complex, Debidwar,
Comilla. Patients were enrolled from the outpatient
department of the health center from the
beginning of May 2020 to the end of July 2020. All
COVID-19 suspected cases were advised for RT-PCR
test. Consecutive RT-PCR positive eligible mild to
moderate COVID-19 cases of more than 18 years of
age, of both sexes, were enrolled and randomised
into control and intervention arms and followed till
recovery. Randomisation was done using an odd-
even methodology applied to registration numbers,
in a consecutive fashion of 1:1 ratio. Patients with
known pre-existing hypersensitivity to Ivermectin,
pregnant and lactating mothers, and patients
taking other antimicrobials or hydroxychloroquine
were excluded from the study.
IMC J Med Sci 2020; 14(2): 002 2/8

Mild to moderate diseases were defined according
to WHO COVID-19 disease severity classification.
Symptomatic patients without evidence of viral
pneumonia or hypoxia (SpO2 >93% on room air)
were considered as a mild disease and patients
with clinical signs of pneumonia (fever, cough,
dyspnoea, fast breathing) but no signs of severe
pneumonia, including SpO2≥ 90% on room air were
considered as a moderate disease [6]. Upon
enrollment, all COVID-19 cases received
symptomatic treatment which included
antipyretics, cough suppressants, and capsule
doxycycline (100 mg every 12 hours for seven days)
to treat possible community-acquired pneumonia
as part of the local working protocol and this
treatment schedule was termed as ‘usual care’. The
control arm continued to receive the ‘usual care’,
and the intervention arm in addition to usual care,
received single dose of ivermectin 200
micrograms/kg on the day 1 of randomisation.
Procedure for enrollement of cases is shown in
Figure-1. The selected cases were treated on an
OPD basis.
Repeat RT-PCR was performed on day 10 after the
first positive test result. Data were collected in a
semi-structured questionnaire devised for the
study by the research team. Both face-to-face and
telephonic communication were used for follow-up
and data collection.
Outcome measures
The outcome end point was the time needed for
resolution of fever, cough, shortness of breath and
finally, full recovery from all symptoms and the
negative result of repeat RT-PCR on day 10.
Recovery time was defined as time required for the
resolution of symptom(s) from the date of
enrolment in the study as well as from the onset of
initial illness.
Ethics and statistical analysis
Permission was taken from the head of the health
centre. Informed written consent from the patients
was obtained before enrolment.
.
Fig-1: Sample selection flow chart
1657
•Total number of suspected
patients advised for RT-PCR
during the study period
416
•RT-PCR +ve patients
82
•After exclusion of 334 patients
based on exclusion crieria
•Recruted and randomised
62
•Finaly selected for analysis after exclusion
of 18 patients due to symptoms more
than 7 days at presentation and 2 patients
due to insufficient data
IMC J Med Sci 2020; 14(2): 002 3/8

After collection, data editing and clearing were
done manually and prepared for data entry and
analysis by using SPSS version 20. The data was
checked for any omissions, irrelevance, and
inconsistencies. The omissions were corrected by
repeating history. Irrelevant and inconsistent data
were discarded. Finally, 62 patients were included
in the intention-to-treat analysis. The unpaired t-
test was used to compare the means between
control and intervention arms. Crosstab and chi-
square tests were used to compare demographic
parameters between control and intervention
arms. P-value of less than 0.05 was taken as
significant.
Results
Initially, 82 patients were recruited; of these, 62
patients who presented within seven days of onset
of symptoms were finally selected for analysis.
Twenty patients were excluded as 18 had
symptoms for more than seven days at the time of
enrollment and two other patients had insufficient
data. There were 30 patients in the control arm,
and 32 patients were in the intervention arm. The
mean age of the all enrolled cases was 39.16±12.07
years. The mean age of cases in control and
intervention arms were not significantly different
(39.97±13.24 versus 38.41±11.02 years; p>0.05).
Out of 62 cases, 44 (71.0%) were male and 18
(29.0%) were female. With regard to category, 50
(80.6%) and 12 (19.4%) were mild and moderate
COVID-19 cases respectively. The predominant
symptoms of the study population were fever (50,
80.6%), followed by cough (42, 67.7%). There was
no statistically significant differences in baseline
demographic and clinical parameters between
control and intervention arms except sore throat
(Table-1).
Table-2 shows the duration of different symptoms
of the study participants at the time of enrolment.
Mean duration of different symptoms of the cases
in both control and intervention arm was not
significantly different (p>0.05) at the time of
enrolment.
Table-1: Demographic and clinical characteristics of the patients at the time of enrolment in the study
(n=62)
Characteristics
Total
N=62
n (%)
Control arm
(N=30)
n (%)
Intervention arm
(N = 32)
n (%)
p value
Male
44 (71.0)
21 (70.0)
23 (71.9)
>.05
Female
18 (29.0)
9 (30.0)
9(28.1)
Presenting symptoms
Fever
50 (80.6)
23 (76.7)
27 (84.4)
>.05
Cough
42 (67.7)
21 (70.0)
21 (65.6)
>.05
Shortness of breath)
12 (19.4)
6 (20)
6 (18.8)
>.05
Sore throat
14 (22.6)
11 (36.7)
3 (9.4)
<.05
Anosmia
14 (22.6)
5 (16.7)
9 (28.1)
>.05
Dysgeusia
3 (4.8)
2 (6.7)
1 (3.1)
>.05
Diarrhoea
6 (9.7)
2 (6.7)
4 (12.5)
>.05
Myalgia
22 (35.5)
8 (26.7)
14 (43.8)
>.05
Fatigue
12 (19.4)
7 (23.3)
5 (15.6)
>.05
Headache
7 (11.3)
5 (16.7)
2 (6.3)
>.05
Rhinorrhoea
8 (12.9)
4 (13.3)
4 (12.5)
>.05
Severity of illness
Mild
50 (80.6)
24 (80.0)
26 (81.3)
>.05
Moderate
12 (19.4)
6 (20)
6 (18.8)
Note: p value calculated by comparing between control and intervention arm.
IMC J Med Sci 2020; 14(2): 002 4/8

There were no significant differences with regard
to recovery time for fever, cough, shortness of
breath and complete resolution of all symptoms
between control and intervention arms either from
the date of enrolement or from the onset of illness
(Table-3 and Table-4). Therefore, the duration of
the illness from onset to recovery was not
significantly different among the of COVID-19 cases
in two study arms.
Repeat RT-PCR was done in 40 patients on day ten
since the first positive RT-PCR. Repeat RT-PCR for
SARS-CoV-2 was negative in 37 (92.5%) patients.
Table-2: Duration of symptoms of patients in intervention and control arms at the time of enrolment (n=62).
Symptoms
Mean ( ± SD) duration in days
All patients
Control arm
Intervention arm
pa
Fever
3.92±2.12
4.00±2.17
3.85±2.11
>.05
Cough
3.76±2.07
3.62±2.27
3.90±1.89
>.05
Shortness of breath
2.42±1.31
3.00±1.27
1.83±1.17
>.05
Fatigue
4.00±2.13
4.71±2.36
3.00±1.41
>.05
Myalgia
3.67±1.86
4.50±3.54
3.25±.96
>.05
Note: a=Compared between control and intervention arm by student’s t test
Table-3: Time required for the resolution of symptoms of cases in control and intervention arms from the
date of enrolment in the study
Symptoms
Recovery time following enrolment in the
study
95% Confidence Interval of
the difference of means
Control group
Intervention group
p
value
Lower
Upper
Mean ±SD
(days)
Mean ±SD
(days)
Complete recoverya
6.33±4.23
5.31±2.48
>.05
-0.766
2.808
Fever
3.18±2.61
3.33±2.18
>.05
-1.729
1.415
Shortness of breath
6.33±3.67
4.83±1.72
>.05
-2.187
5.187
Fatigue
5.67±3.62
6.00±4.85
>.05
-6.097
5.430
Note: aResolution of all symptoms. Some parameters are excluded from the analysis due to inadequate data
Table-4: Time required for the resolution of symptoms of cases in control and intervention arms from the
date of onset of illness
Symptoms
Recovery time from the onset of initial
symptoms
95% Confidence Interval of
the difference of means
Control group
Intervention group
p
Lower
Upper
Mean ±SD
(days)
Mean ±SD
(days)
Complete recoverya
11.50±5.32
10.09±3.24
>.05
-.860
3.672
Fever
6.43±2.45
6.48±3.39
>.05
-1.755
1.662
Cough
10.45±3.70
9.23±3.22
>.05
-.883
3.338
Shortness of breath
8.86±4.74
6.67±1.86
>.05
-2.294
6.675
Fatigue
9.57±3.65
9.00±3.61
>.05
-4.164
5.306
aResolution of all symptoms; *Some parameters are excluded from the analysis due to inadequate data
IMC J Med Sci 2020; 14(2): 002 5/8

Results of repeat RT- PCR were not significantly
different between control and intervention arms
(Table-5).
Table-5: Result of repeat RT-PCR on 10th day (n=40)
Repeat
RT-PCR
test
Intervention
arm
n (%)
Control
arm
n (%)
Sig
Positive
2 (10)
1(5)
p>.05
Negative
18 (90)
19 (95)
Total
20
20
Discussion
In this open-label, single-centre, intention-to-treat
randomised controlled study involving mild to
moderate RT-PCR confirmed COVID-19 patients, a
200 micrograms/kg single dose of ivermectin added
to usual care did not provide better clinical
outcomes in terms of duration of symptomatic
recovery and rate of repeat RT-PCR negativity.
The COVID-19 pandemic has caused a tremendous
burden on healthcare facilities around the world,
due to its rapid spread with devastating
consequences. Currently, no medication is
recommended for mild to moderate COVID-19. The
development of a whole new molecule takes time,
so researchers are also trying to explore the
effectiveness of existing drugs against SARS-CoV-2,
which have already been shown to be effective in
treating similar viruses. Several of these drugs are
currently in use without having apparent benefits.
Hydroxychloroquine and chloroquine were the
most widely used drugs. Initial observational
studies showed significant benefit of these drugs
against COVID-19 [17,18]. However, later in RCTs,
these presumed benefits were negated [19,20].
Ivermectin is also one of these drugs, widely used
as a treatment for the early stage of COVID-19. This
drug has shown its in-vitro activities against SARS-
CoV-2 [12]. Initial observational studies have also
shown benefits, but no RCTs have been published
yet to prove its benefit over usual care in the
management of mild to moderate COVID-19 cases.
In this study most of the patients were men; also,
in other Bangladeshi studies, men were found
more affected than women [7,15,21,22] though
internationally, no gender difference was found in
COVID-19 [23]. The predominant symptoms found
in the study was fever followed by cough were
typical of the presentation of COVID-19 [15,24].
There was no significant difference in age, sex, and
disease severity at presentation between the cases
of control and intervention arms and thus
eliminated the selection bias. However, one of the
limitation of our study was that we could not
perform detail biochemical and hemotological
investigations of the study participants. It was due
the fact that the study was carried out at a primary
health care center at a semi-rural settings. Thus, we
were unable to determine the effect of ivermectin
(if any) on the biochemical and haematological
parameters of the COVID-19 cases. However, the
study emphasis was on the clinical outcome
following ivermectin treatment.
A recent RCT in Bangladesh, reported ivermectin-
doxycycline combination superior to
hydroxychloroquine-azithromycin combination
therapy in mild to moderate COVID-19 cases [21].
However, the time difference to become symptom-
free and the time difference for negative RT-PCR
were not statistically significant (consecutively
p=0.071 and p= 0.2314). The mean duration of
symptomatic recovery was 5.93 days (5 to 10 days) in
the ivermectin group and 6.99 days (4 to12 days) in
the hydroxychloroquine group. In our study, the
mean duration of symptomatic recovery was not
different between the control and intervention arms.
Another study compared the viral clearance by
ivermectin+doxycycline with hydroxychloroquine
plus azithromycin in patients with COVID-19 [15]. In
this study, Rahman M et al. compared the benefits
of viral clearance between the groups mentioned
above and found better viral clearance in the
ivermectin group. However, the results of the two
groups were assessed at different time frames,
making comparisons disputed and was criticised in
an editorial comment in the same issue of the
journal [25].
The ineffectiveness of ivermectin on the overall
COVID-19 outcome is not unexpected. Available
pharmacokinetic data from clinically relevant and
excessive dose studies suggest that the ivermectin
concentration required to inhibit SARS-CoV-2 in
humans is unlikely to be attainable in serum and
IMC J Med Sci 2020; 14(2): 002 6/8

tissue with known dosing regimens [13]. In a brief
review of ivermectin and COVID-19, Chaccour et al.
concluded that ivermectin is incorrectly used to
treat COVID-19 without scientific evidence of
demonstrable efficacy and safety [16].
In conclusion, adding ivermectin to usual care in
the management of mild to moderate COVID-19
patients did not show any benefit. However, since
the sample size was small, future multicentre
studies with a larger sample size could be
conducted to confirm the outcome.
Author’s contributions
CSP was involved in study planning, patient
recruitment and data collection; NC was involved in
patient recruitment, data collection, data entry; MIS
did patient recruitment, data entry; WMMH did
study planning, data analysis and manuscript writing.
Conflict of Interest
The authors declare no conflict of interest.
Funding
This study was self-financed.
References
1. Zheng J. SARS-CoV-2: an Emerging Coronavirus
that Causes a Global Threat. Int J Biol Sci. 2020;
16(10): 1678-85.
2. Cucinotta D, Vanelli M. WHO Declares COVID-19
a Pandemic. Acta bio-medica: Atenei Parmensis
[Internet]. 2020; 91(1): 157-160.
3. Li G, De Clercq E. Therapeutic options for the
2019 novel coronavirus (2019-nCoV). Nat Rev
Drug Discov. 2020; 19(3): 149-50.
4. De Clercq E. Potential antivirals and antiviral
strategies against SARS coronavirus infections.
Expert Rev Anti Infect Ther. 2006; 4(2): 291-302.
5. Disease Control Division. Directorate General
of Health Services. Ministry of Health & Family
Welfare. Government of the People’s Republic
of Bangladesh. National Guidelines on Clinical
Management of Coronavirus Disease 2019
(COVID-19). Version 7.0. Published, 28 May
2020.
6. World Health Organization. Clinical management
of COVID-19: interim guidance, 27 May 2020.
World Health Organization; 2020.
7. Alom M, Murshed R, Bhiuyan E, Saber S, Alam
R, Robin R. A Case Series of 100 COVID-19
Positive Patients Treated with Combination of
Ivermectin and Doxycycline. J Bangladesh Coll
Phys Surg. 2020; 38(Supplement Issue): 10-15.
8. Sharun K, Dhama K, Patel SK, Pathak M, Tiwari
R, Singh BR, et al. Ivermectin, a new candidate
therapeutic against SARS-CoV-2/COVID-19.
Ann Clin Microbiol Antimicrob. 2020; 19(1): 23.
9. Heidary F, Gharebaghi R. Ivermectin: a
systematic review from antiviral effects to
COVID-19 complementary regimen. J Antibiot
(Tokyo). 2020; 73(9): 593-602.
10. Mastrangelo E, Pezzullo M, De Burghgraeve T,
Kaptein S, Pastorino B, Dallmeier K, et al.
Ivermectin is a potent inhibitor of flavivirus
replication specifically targeting NS3 helicase
activity: new prospects for an old drug. J
Antimicrob Chemother. 2012; 67(8): 1884-
1894.
11. Varghese FS, Kaukinen P, Gläsker S, Bespalov
M, Hanski L, Wennerberg K, et al. Discovery of
berberine, abamectin and ivermectin as
antivirals against chikungunya and other
alphaviruses. Antiviral Res. 2016; 126: 117-124.
12. Caly L, Druce JD, Catton MG, Jans DA, Wagstaff
KM. The FDA-approved drug ivermectin
inhibits the replication of SARS-CoV-2 in vitro.
Antiviral Res. 2020; 178: 104787.
13. Momekov G, Momekova D. Ivermectin as a
potential COVID-19 treatment from the
pharmacokinetic point of view: antiviral levels
are not likely attainable with known dosing
regimens. Biotechnol Biotechnol Equip. 2020;
34(1): 469-74.
14. Rajter JC, Sherman M, Fatteh N, Vogel F, Sacks
J, Rajter J-J. ICON (Ivermectin in COvid
Nineteen) study: Use of Ivermectin is
Associated with Lower Mortality in
Hospitalized Patients with COVID19. medRxiv.
2020:2020.06.06.20124461.
15. Rahman M, Iqbal S, Islam M, Niaz M, Hussain T,
Siddiquee T. Comparison of Viral Clearance
IMC J Med Sci 2020; 14(2): 002 7/8

between Ivermectin with Doxycycline and
Hydroxychloroquine with Azithromycin in
COVID-19 Patients. J Bangladesh Coll Phys
Surg. 2020; 38(Supplement Issue): 5-9.
16. Chaccour C, Hammann F, Ramón-García S,
Rabinovich NR. Ivermectin and COVID-19:
Keeping Rigor in Times of Urgency. Am J Trop
Med Hyg. 2020; 102(6): 1156-7.
17. Gautret P, Lagier J-C, Parola P, Hoang VT,
Meddeb L, Mailhe M, et al.
Hydroxychloroquine and azithromycin as a
treatment of COVID-19: results of an open-
label non-randomized clinical trial. Int J
Antimicrob Agents. 2020; 56(1): 105949-.
18. Arshad S, Kilgore P, Chaudhry ZS, Jacobsen G,
Wang DD, Huitsing K, et al. Treatment with
hydroxychloroquine, azithromycin, and
combination in patients hospitalized with
COVID-19. Int J Infect Dis. 2020; 97: 396-403.
19. Borba MGS, Val FFA, Sampaio VS, Alexandre
MAA, Melo GC, Brito M, et al. Effect of High vs
Low Doses of Chloroquine Diphosphate as
Adjunctive Therapy for Patients Hospitalized
With Severe Acute Respiratory Syndrome
Coronavirus 2 (SARS-CoV-2) Infection: A
Randomized Clinical Trial. JAMA Netw Open.
2020; 3(4): e208857-e.
20. Cavalcanti AB, Zampieri FG, Rosa RG, Azevedo
LCP, Veiga VC, Avezum A, et al.
Hydroxychloroquine with or without
Azithromycin in Mild-to-Moderate Covid-19. N
Engl J Med. 2020.
21. Chowdhury ATMM, Shahbaz M, Karim MR,
Islam J, Guo D, He S. A Randomized Trial of
Ivermectin-Doxycycline and
Hydroxychloroquine-Azithromycin therapy on
COVID19 patients. Research Square; 2020.
22. Bhuyan MA, Al Mahtab M, Ashab E, Haque MJ,
Hoque SMM, Faizul Huq A, et al. Treatment of
COVID-19 Patients at a Medical College
Hospital in Bangladesh. Euroasian J
Hepatogastroenterol. 2020; 10(1): 27-30.
23. Spagnolo PA, Manson JE, Joffe H. Sex and
Gender Differences in Health: What the COVID-
19 Pandemic Can Teach Us. Ann Intern Med.
2020.
24. Zhu J, Ji P, Pang J, Zhong Z, Li H, He C, et al.
Clinical characteristics of 3062 COVID-19
patients: A meta-analysis. J Med Virol. 2020.
25. Rahim M, Mostafi M. Re-purposive Use of
Drugs in COVID-19: A Wake-up Call. J
Bangladesh Coll Phys Surg. 2020;
38(Supplement Issue): 3-4.
IMC J Med Sci 2020; 14(2): 002 8/8