Clinical Trial of Black Seeds Against COVID -19 in Kirkuk City/ Iraq

Abstract

In order to cope with Coronavirus Disease 2019 (COVID-19) pandemic, there is an urgent need for effective prevention and control measures. This study aims to explore the positive action of black seeds (BS) against COVID-19 in patients involved in the trail. It is a descriptive, comparative, and open-label study. In our study, (419) participants were divided into two groups .The studied participants included patients which received standard care treatment as a control group (CON) , while the (BS) group were patients received black seeds at a 40 mg/kg dose orally, once daily for 14 days plus standard protocol of treatment. The evidence of BS efficacy was obvious in the severity and outcome of infection with covid-19. A significantly higher severity of infection among control group 44 (17.0%) than the black seed group were noticed; the control group also showed 14 deaths (5.4%), while there were no deaths in black seeds group (0.0%). Thus, we can conclude that black seed is very effective in reducing the severity of covid-19 and preventing death in infected patients.

Full text

Indian Journal of Forensic Medicine & Toxicology, July-September 2021, Vol. 15, No. 3 3393
Clinical Trial of Black Seeds Against COVID – 19 in Kirkuk
City/ Iraq
Kadhim Ali Abbas Al-Haidari1, TunjaiNamiq Faiq2 , OzdanAkram Ghareeb3
1Family Physician inKirkuk Rehabilitation Center, Kirkuk Health Directorate, Iraq, 2Consultant Otolaryngologist
in Kirkuk General Hospital, Kirkuk Health Directorate, Iraq, 3Assistant Lecturer in Department of Community
Health Techniques, Kirkuk Technical Institute
Abstract
In order to cope with Coronavirus Disease 2019 (COVID-19) pandemic, there is an urgent need for effective
prevention and control measures. This study aims to explore the positive action of black seeds (BS) against
COVID-19 in patients involved in the trail. It is a descriptive, comparative, and open-label study. In our
study, (419) participants were divided into two groups.The studied participants included patients which
received standard care treatment as a control group (CON) , while the (BS) group were patients received
black seeds at a 40 mg/kg dose orally, once daily for 14 days plus standard protocol of treatment. The
evidence of BS efcacy was obvious in the severity and outcome of infection with covid-19. A signicantly
higher severity of infection among control group 44 (17.0%) than the black seed group were noticed; the
control group also showed 14 deaths (5.4%), while there were no deaths in black seeds group (0.0%). Thus,
we can conclude that black seed is very effective in reducing the severity of covid-19 and preventing death
in infected patients.
Key words : Pandemic disease, COVID-19, Infection,medicinal plant, , Black seeds
Corresponding author:
Ozdan Akram Ghareeb
Assistant lecturer :-
Email: krciraq@gmail.com
Introduction
COVID19 storm shows its lethal face worldwide and
it is still difcult to predict how long it will last, and how
deadly it could be (1). This disease mainly affected social
life, particularly health care services in addition to daily
treatment practices since the world health organization
(WHO) declared SARS CoV-2 as a global pandemic
in early 2020 (2-5). The COVID-19 infection primarily
affects the respiratory system and is presented with
cough, fever and sometimes pneumonia and shortness
of breath and patients may deteriorate due to acute
respiratory distress syndrome, as well as other clinical
manifestations such as cardiac, gastrointestinal and
central nervous system (6-10). The WHO situational report
recorded more than 20 million laboratory-conrmed
cases and 700 thousand global deaths since August 13,
2020 (11). The rst identied case of COVID-19 in Iraq
was in Najaf province in an Iranian student who came
from Iran on 24 February 2020, followed by detection
of the virus in 4 members of a family in Kirkuk
province on 25 February who have previously visited
Iran (12,13). There is a globally very high challenge of
COVID-19 because of the lack of proven treatment and
its complicated transmission (14,15). However, presence
of several preventive health measures may be helpful
in resolving primary complications among patients.
Since April 2, 2020, there have been 291 active clinical
specic trials to cope with COVID-19, including 109
pharmacological therapeutic trials to treat COVID-19
among adult patients (16).
Till now, herbs are widely used to treat several
diseases in many countries due to its excellent culturing
compatibility with the human body and its safety(17).This
has led to a search for therapeutic alternatives, particularly
among medicinal plants(18). Nigella sativa belongs to the

3394 Indian Journal of Forensic Medicine & Toxicology, July-September 2021, Vol. 15, No. 3
family Ranunculacea, and it is also known as black seed,
black cumin seed, Habatul Baraka, Habatussawda and
Kalonji(19). N. sativa seeds are believed to have healing
powers in traditional medicine and have long been used
for treating a wide range of disorders including allergy,
headaches, bronchial asthma, back pain, infections,
obesity, hypertension and gastrointestinal problems (20-
22). The present study aims to evaluate the therapeutic
value of black seeds in treatment of Covid19.
Methodology
This study was conducted on patients diagnosed
with covid-19. It was done during the period between
5th September and 15th November 2020 in Kirkuk city,
Iraq. It is a randomized and open-label study, which was
approved by the Institutional Ethics Committee. All the
participants gave voluntary written and informed consent
for this study. The diagnosis of infection with covid-19
was made on the basis of polymerase chain reaction
(PCR) teston throat swab samples. Participants aged 13-
90 years of both genders were enrolled in this trial. The
included participants were randomized into two groups,
participants of group CON (259) who received standard
care treatmentaccording to the standard protocol and
considered as a control group, and (160) participants
of BS group who received black seeds40 mg/kg orally
once daily for 14 days plus standard protocol.Standard
care therapy was as recommended by the clinical
management instructions for covid-19 established by
the Iraqi Ministry of health. Black seed of 100% purity
was used in the study which was commercially available
and purchased from the local market in Kirkuk, Iraq.
Patients having hypertension (HYP), ischemic heart
disease (IHD), diabetes mellitus (DM), bronchial asthma
(AS), morbid obesity (MO) or patients having more than
one comorbidity (MIX) were included in the study too.
While patients with severe illnesses requiring admission
to intensive care unit,end stage renal disease requiring
dialysis, severe chronic liver disease, pregnancy or
breast feedingand allergy to any study medication were
excluded from this trail. The severity of infection was
grouped as: mild disease including patients with mild
symptoms of covid-19 without evidence of pneumonia;
moderate infection when the patient had fever with
pneumonia. Whilst severe class used for patients with:
a- respiratory distress RR> than 30/m in adults, b- blood
oxygen saturation less than 93% on ambient air, c- PaO2
/ FiO2 less than 300, d- lung inltrates >50% of the
lung eld within 24 hours. All the enrolled individuals
were regularly followed up. Physical examination and
investigations were done at 0, 14, 28, 42, 56 and 70
days of the study. A physical examination including
assessment of vital signs was done at the start of the
study and following the visits. Further laboratory tests,
chest X-ray and CT scan were performed whenever
necessary.
Statistical Analysis
Data analysis were done using the IMB SPSS
version 26.Proportions and 95% condence intervals
(95% CI) were calculated using descriptive statistics. P
values were calculated by Chi-square test, using analytic
statistics. Values were considered to be statistically
signicant when the obtained P-value was less than 0.05.
Results
Baseline demographics of trial groups are shown
in table (1).Groups included 419 patients, 212 (50.6%)
of them were males and 207 (49.4%) females.The age
groups ranged from (13-18) to (> 65) years.Table (2)
showed the effectiveness of black seeds on covid-19
among the participants. Cross tabulation was performed
to describe the association between black seeds group
and severity as well as the nal outcome of infection
with covid19. Results of this study showed less infection
severity in BS group, only 2 cases (1.3%) in comparison
with 44 cases (17.0%) in the control group. In addition,
there was 14 deaths (5.4%) as an outcome of infection,
while no death was recorded in the BS group during the
period of the study. On the other hand, the severity in
the BS group was restricted to the age group (>65) years
1.3%. There was no statistically signicant differences
between the participants with respect to gender and
comorbidities as shown in table (3).

Indian Journal of Forensic Medicine & Toxicology, July-September 2021, Vol. 15, No. 3 3395
Table (1): Distribution of trial patients according to: age/ year , gender and comorbidity
Baseline demographics Control (N=259) Black Seeds (N= 160) Total ( N=419) p value
Age
13-18 30 (7.2%) 11 (2.6%) 41 (9.8%)
0.142
19-39 109 (26.0%) 58 (13.8%) 167 (39.9%)
40-65 106 (25.3%) 82 (19.6%) 188 (44.9%)
> 65 14 (3.3%) 9 (2.1%) 23 (5.5%)
Gender
Male 132 (31.5%) 80 (19.1%) 212 (50.6%)
0. 848
Female 127 (30.3%) 80 (19.1%) 207 (49.4%)
comorbidity
HYP 22 (5.3%) 15 (3.5%) 37 (8.8%)
0. 263
AS 5 (1.2%) 5 (1.2%) 10 (2.4%)
DM 9 (2.1%) 5 (1.2%) 14 (3.3%)
IHD 4 (1.0%) 3 (0.7%) 7 (1.7%)
MO 1 (0.2%) 5 (1.2%) 6 (1.4%)
MIX 22 (5.3%) 8 (1.9%) 30 (7.2%)
None 196 (46.8%) 119 (28.4%) 315 (75.2%)
Table (2): Effect of black seeds on severity and outcome of covid-19 infection among the participants
Clinical presentation Control Black Seeds Pvalue
Severity of infection
Mild 190 (73.4%) 151 (94.4%)
<0.001
Moderate 25 (9.7%) 7 (4.4%)
Sever 44 (17.0%) 2 (1.3%)
Total 259 (100%) 160 (100%)
Outcome of infection
Cure 245(94.6%) 160(100.0%)
0.003
Death 14 (5.4%) 0 (0.0%)
Total 259 (100%) 160 (100%)

3396 Indian Journal of Forensic Medicine & Toxicology, July-September 2021, Vol. 15, No. 3
Table (3): Severity levels of infection with covid 19 among BS group according to age, gender
andcomorbidity
Parameters
Severity levels
Total
N=160 P value
Mild
N=151
Moderate
N=7
Severe
N=2
Age
13-18 11 (6.9%) 0 (0.0%) 0 (0.0%) 11 (6.9%)
< 0.001
19-39 56 (35.0%) 2 (1.3%) 0 (0.0%) 58 (36.3%)
40-65 77 (48.1%) 5 (3.1%) 0 (0.0%) 82 (51.2 %)
> 65 7 (4.4%) 0 (0.0%) 2 (1.3%) 9 (5.6 %)
Gender
Male 74 (46.3%) 5(3.1%) 1(0.6%) 80 (50%)
0.510
Female 77 (48.1%) 2(1.3%) 1(0.6%) 80 (50%)
Comorbidity
HYP 15 (9.4%) 0 (0.0%) 0 (0.0%) 15 (9.4%)
0.036
AS 4 (2.5%) 1 (0.6%) 0 (0.0%) 5 (3.1%)
DM 4 (2.5%) 1 (0.6%) 0 (0.0%) 5 (3.1%)
IHD 2 (1.3%) 1 (0.6%) 0 (0.0%) 3 (1.9%)
MO 5 (3.1%) 0 (0.0%) 0 (0.0%) 5 (3.1%)
MIX 7 (4.4%) 0 (0.0%) 1 (0.6%) 8 (5.0%)
None 114 (71.3%) 4 (2.5%) 1 (0.6%) 119 (74.4%)
Discussion
There is a direct association of the therapeutic
effect of herbal medicine on its chemical compositions.
Nigella sativa seed is a precious herbal medicine
since it is traditionally used in treating many diseases.
Owing to its wide range medical applications, this herb
plant underwent extensive phytochemical studies, and
numerous different compounds were isolated from it.
The black cumin seeds contain a yellowish xed oil,
amino acids, fats, proteins, reducing sugars, alkaloids,
minerals, organic acids, tannins, crude bers as well as
vitamins (23,24). It has anti-viral, anti-inammatory, anti-
oxidant, anti-histaminic, anti-microbial, analgesic and
has immuno-modulation activity. These values make it a
strong candidate for covid-19 treatment (25).

Indian Journal of Forensic Medicine & Toxicology, July-September 2021, Vol. 15, No. 3 3397
N. sativa can kill or inhibit the virus via a multi
prong strategy through targeting several viral sites or
through host-virus interaction. Thus, it is distinguished
from the other antiviral agents by targeting of the
specic structure or pathway of SARS-CoV-2 infections
(26). Previous studies portended that many avonoids and
phenolic compounds that exist in N.sativa seeds bound
or docked to the SARS-CoV-2 spike protein–human
angiotensin converting enzyme-2 receptor complexes
(27,28).
In addition, it has been hypothyzed that the antiviral
effectiveness of N.sativa can be attributed to high
serum levels of interferon-gamma, raised CD4 counts,
augmented suppressor functions as well as enhanced
macrophage numbers (29). An in-vitro study, linoleic acid
also showed synergy with remdesivir, which is used as
COVID-19 drug, leading to suppression of SARS-CoV-2
replications (30). On the other hand, the pathogenesis of
SARS-CoV-2 infection is related to the overproductions
of reactive oxygen species (ROS) and deprivations of
the antioxidant systems (31). Thymoquinone which is the
active ingredient in N. sativa seeds has demonstrated
effects in reducing oxidative stress (32). Also it modulates
or inuences the immune-modulators such as IL-1, IL-6,
IL-10, IL-18, TNF-α and the nuclear factor-κB, therefore,
can signicantly reduce the cytokine storm chances and
consequent mortalities (33). Moreover, N. sativa seeds
inhibited the inammatory effects of the airways. On the
other side, its immune-modulatory and anti-histaminic
effects can prevent secondary infections. N. sativa seeds
has anti-hypertensive, anti-diabetic, cardio-protective
and bronchodilatory properties which make it more
benecial to control such diseases. While its anti-platelet
and anti-coagulant effects may also safeguard patients
with COVID from thromboembolic complication, which
is the most important cause of complication and death
(34-36).
This study has several limitations. The uncontrolled
factors that potentially affect the results of this study
included patient’s diet such as taking some medical
nutritional supplements. Besides, genetic factors, and
psychological conditions received less attention in
this study. For this reason, further clinical studies and
double blind studies are necessary to conrm the role of
BS in the treatment of Covid19 which seems crucial to
consider in the treatment protocols.
Conclusions
It can be concluded that N. sativa seeds have been
proven as a safe andpotent adjunctive therapeutic
agent against COVID-19. It reduces complications and
prevents deaths. So, it is likely to lower the burden on
health care systems in a signicant manner.
Ethical Clearance : All experimental protocols
were approved by the Institutional Ethics Committee.
All the participants gave voluntary written and informed
consent for this study.
Source of Funding: Self
Conict of Interest: The authors have declared no
conict of interest
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