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THERAPEUTIC EFFECT OF VITAMIN A ON COVID-19 PATIENTS AND ITS PROPHYLACTIC EFFECT ON CONTACTS

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role of vitamin A on covid-19 patients and its prophylactic effect on contacts
Sys Rev Pharm 2021;12(1):207-210
A multifaceted review journal in the field of pharmacy
Systematic Reviews in Pharmacy Vol 12, Issue 1, Jan-Feb 2021
207
THERAPEUTIC EFFECT OF VITAMIN A ON COVID-19
PATIENTS AND ITS PROPHYLACTIC EFFECT ON
CONTACTS
Mahmood M. Al-Sumiadai1, Hazim Ghazzay2, Rafi Khaleel Al-Ani3
1DCH/ Ministry of Health- Anbar health directorate/ Ramadi city/ MOH/Iraq.
2F.I.C.M.S / Internal medicine/Department of medicine / Collage of medicine / university of Anbar/Iraq.
3CIB/ Ministry of Health- Anbar health directorate/Iraq
alsumaidaidrmah@gmail.com
ABSTRACT
Background: No other similar study was done on the role of
vitamin A in the treatment of COVID-19.
Objective: To find the effect of vitamin A on patients with
COVID-19 and its protective effect on contacts.
Patient and Methods: A cross-sectional study was done on two
groups. The first group of 100 diagnosed mild to moderate
patients with COVID-19, 50 patients received two doses of
vitamin A (200,000 I.U.) for two days, another 50 patients
received a placebo. Data about clinical features, SPO2, and the
mean duration of symptoms collected after 24 and 48 hours from
the administration, in addition to the number of patients who
deteriorate their SPO2. A second group was contacted to patients
diagnosed with COVID-19, part of them received two doses
(200,000 I.U.) of vitamin A and others received a placebo. The
comparison was between the percentage of getting the infection
and the duration of symptoms among those who got the
infection.
Results: A significant improvement in symptoms, shorter
duration of illness, with a lower number of patients who
deteriorate their SPO2 among patients given vitamin A
compared to control. A lower incidence of infection among
contacts who received vitamin A in comparison to contacts
received placebo with shorter duration of symptoms among
those who got the infection.
Conclusions; A great benefit of the use of vitamin A in patients
with COVID-19 and to contacts. Adding vitamin, A to the
protocol management of COVID-19 is recommended.
Keywords; COVID-19, Vitamin A, Therapy, Contacts,
Prophylaxis.
Running title; Vitamin A in treatment of COVID-19.
INTRODUCTION
Coronavirus disease 2019 (COVID-19) is caused by SARS-
CoV-2, a newly emergent coronavirus, that was first
recognized in Wuhan, China, in December 2019. Genetic
sequencing of the virus suggests that it is a beta coronavirus
closely linked to the SARS virus.By way of definition, a
symptomatic COVID-19 case is a person who has developed
signs and symptoms suggestive of COVID-19.1
Vitamin A is a fat-soluble micronutrient that cannot be
synthesized de novo by mammals, thus it is an obligatory
dietary factor. It is now well established that all vertebrates
require vitamin A for adequate growth, cell and tissue
differentiation, vision, development and function of the
immune system, and survival.2Concentrations of preformed
vitamin A are highest in liver and fish oils. Other sources of
preformed vitamin A are milk and eggs, which also include
some provitamin A. Most dietary provitamin A comes from
leafy green vegetables, orange and yellow vegetables, tomato
products, fruits, and some vegetable oils .3
The doses of vitamin A used in children with measles
(100,000-200,000 IU) are given once or twice.2The
recommended dose in children for more than one year and
adults with xerophthalmia (vitamin A deficiency) is (200,000
IU) for two days. 4Dosages of vitamin A in the order of 100
times the recommended daily allowance are required to
produce toxicity in adults, and for this reason, acute toxicity
is quite uncommon. Symptoms of acute toxicity include
gastrointestinal upset and neurological symptoms of
headaches, blurred vision, vertigo, and muscular
incoordination.5Intakes of vitamin A greater than 10,000 IU
per day are not recommended for well-nourished pregnant
women.6
The mechanism of vitamin A on infections could be by
enhancing the immune response by deferent ways, including;
morphological formation of the epithelium, epithelial
keratinization, and functional maturation of epithelial cells
which are regarded as the first-line defense against pathogen
invasion.7,8 Regulate the apoptosis of thymocytes.9-11 Induces
T cell migration to the thymus where they developed into
mature T cells.12,13 Promoting T cell activation and T helper
cell responses at minimal levels.14 Lastly, the effect of
vitamin A on B cell may by enhancing antibody production,
15,16 and regulating B cell activity.17,18
There are many applications of using vitamin A in the
treatment of infectious diseases including;
1. Tuberculosis. A longitudinal cohort study of tuberculosis
Therapeutic Effect Of Vitamin A On Covid-19 Patients And Its Prophylactic Effect On
Contacts
208 Systematic Reviews in Pharmacy Vol 12, Issue 1, Jan-Feb 2021
Systematic Reviews in Pharmacy Vol 12, Issue 2, Jan-Feb 2021
showed that vitamin A deficiency is dose-dependently
correlated to the occurrence of tuberculosis.19-21
2. Acquired Immune Deficiency Syndrome (AIDS). Vitamin
A, vitamin C, and vitamin E are all-natural antioxidants, and
by inhibiting the oxidative stress of the organism, it is
postulated that these vitamins can ameliorate the progression
of AIDS.22,23
3. Infectious diseases in children, vitamin A has
demonstrated a therapeutic effect, to some extent, in diseases
transmitted through the respiratory system, such as
pneumonia and measles in children, or in contagious
digestive diseases in children, such as infantile diarrhea and
hand, foot, and mouth disease. 24-26
Aim of the study;
This study was designed to;
1. Show the therapeutic effect of vitamin A on patients with
COVID 19.
2. Show the protective effect of the vitamin A administration
on contacts.
Subject and method
The study was done in the Anbar governorate west of Iraq
from the beginning of June 2020 on diagnosed patients with
COVID-19 and contacts with diagnosed patients. Informed
consent was taken from families after giving them a full
explanation about the purpose of the study. Two groups of
samples were taken in this study;
1. The first group consists of 100 diagnosed patients with
COVID-19. The selected cases were from mild to moderate
groups, previously healthy, from deferent genders and the
same residential area. 50 patients were given (200,000)
international units of vitamin A on the first day and the same
dose was repeated the next day. Another 50 patients were
given a placebo. The vitamin and placebo were given to the
patients as early as the diagnosis was established.
Exclusion criteria;
a. Patients with old ages >60 years.27
b. Patients with diabetes, hypertension, cardiac disease,
chronic lung disease, cerebrovascular disease, chronic kidney
disease, immunosuppression, and cancer.27
c. Patients with severe disease (respiratory rate > 30
breaths/min, or SpO2 < 90% on room air).1,27
d. Pregnant women.6
A questionnaire data form was prepared for each patient
before giving the vitamin A and after 24 and 48 hours from
therapy about the clinical features and clinical findings
according to WHO classification 1,26 including;
1.Cough.
2.Fever.
3.Fatigability.
4.Loss of smell and taste.
5.Headache.
6.Anorexia.
7. SpO2 .
8. The duration of illness. Recorded from the time of given
vitamin A or placebo.
9.Number and percentage of patients who deteriorated to
severe disease.
2. The second group, the study was done on contacts of
patients with COVID-19 patients. Part of them given
vitamin A (200,000 international unit) on the first day and
repeated the next day, another part of contacts was given a
placebo. The comparison was done on the incidence of
getting COVID-19 from contacts, and the duration of the
symptoms among those who got the infection.
Data collected were checked for accuracy and completeness
and were coded and entered into the Statistical Package for
Social Sciences (SPSS), Descriptive statistics for all studied
variables and Chi-squared test were used and P-value level
<0.05 was considered significant throughout the study.
RESULTS
Regarding the first group of 100 patients. There was a
significant improvement of clinical features (fever, headache,
anorexia, and fatigue) among the 50 patients who received
vitamin A in comparison to the other 50 patients who
received a placebo. Table 1. Mean SPO2 changes among
patients given vitamin A after 24 and 48 hours had a slightly
non-significant improvement than that reported among the
placebo. Table 2. The mean duration of symptoms among
patients given vitamin A was (2.9) while among those
receiving placebo was (4.64). Table 3. Two patients (4%)
from those given vitamin A deteriorate their SPO2 and need
admission in isolation centers while 6 patients (12%) of those
given placebo deteriorate their SPO2 and need admission in
isolation centers. Table 4.
Regarding the second group, contacts to diagnosed COVID-
19. From 97 contacts given vitamin A, only 20 (20.62%) of
them got an infection with COVID-19. While from 112
contacts given placebo 65(58.03%) got the infection with
COVID-19, with a significant difference. The duration of
symptoms of infected contacts was (4.6) among those who
received vitamin A comparing to (6.72) among those given
placebo. Table 5.
DISCUSSION
Studies were limited or not done on the use of vitamin A in
the treatment of COVID-19, but there were many other
studies on the use of vitamin A in the treatment of deferent
virus diseases especially in childhood viral infections like
measles, chickenpox, and infantile diarrhea.28Even in some
bacterial and protozoan infections.29
In the present study, we recommend the trial therapy with
supplementation of vitamin A to patients diagnosed with
COVID-19, and the results were compared with other
patients with the same conditions not supplemented with
vitamin A. Among the first group of mild to moderate
patients, we found a significant improvement in clinical
features, and duration of the symptoms of the disease, in
addition to a lower number of patients who deteriorated to
the severe stage among patients given vitamin A in
comparison to control.
Regarding contacts with patients with COVID-19, in this
study, we found that there was a lower significant difference
in getting the infection in those who received vitamin A from
those not received. And also, we found that symptoms among
contacts who got the infections were shorter in those who
received vitamin A from those not received.
The underlying mechanism of vitamin A in the treatment of
COVID-19, may due to its anti-inflammatory property, or its
effect on enhancing the humeral, cellular, or phagocytic
immunity against the virus, or its repairing action on
epithelial cells of the respiratory tract which needs further
studies to explain this mechanism.
The limitations of the study included a small sample size, and
excluding severe cases.
CONCLUSION
1. There was a significant improvement in signs and
symptoms among patients with mild to moderate severity
whose given vitamin A in comparison to control, with a
shorter duration of symptoms.
2. A significantly lower number of patients who deteriorate
to severe disease among patients given vitamin A.
3. A significantly lower incidence of infection among
contacts received vitamin A with a shorter duration of the
disease.
Therapeutic Effect Of Vitamin A On Covid-19 Patients And Its Prophylactic Effect On
Contacts
209 Systematic Reviews in Pharmacy Vol 12, Issue 1, Jan-Feb 2021
Systematic Reviews in Pharmacy Vol 12, Issue 2, Jan-Feb 2021
RECOMMENDATION
From the above results, the followings are recommended;
1.The addition of vitamin A in the treatment of COVID-19
protocol.
2.The use of vitamin A to all contacts and medical staff.
3. A big case-control study covering the whole country about
the use of vitamin A in the management of COVID-19.
ACKNOWLEDGMENT
I would like to express my deepest gratitude and respect to
the patients and their families, and all medical workers on the
diagnosis of COVID-19 for their helpful advice, patience,
and guidance throughout the execution of this study.
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TABLES
Therapeutic Effect Of Vitamin A On Covid-19 Patients And Its Prophylactic Effect On
Contacts
210 Systematic Reviews in Pharmacy Vol 12, Issue 1, Jan-Feb 2021
Systematic Reviews in Pharmacy Vol 12, Issue 2, Jan-Feb 2021
Table.1. Number and percentage of patients among different symptoms before and after vitamin A and placebo administration.
Symptoms
Variables
No and % after 24
hr
No and % after 48 hr
Significant
Fever
Vitamin A
15 (30%)
10 (20%)
P=0.006
Placebo
25 (50%)
30 (60%)
Anorexia
Vitamin A
13 (26%)
11 (22%)
P=0.002
Placebo
23 (46%)
20 (40%)
Headache
Vitamin A
18 (36%)
12 (24%)
P<0.0001
Placebo
32 (64%)
37 (74%)
Fatigability
Vitamin A
22 (44%)
14 (28%)
P<0.0001
Placebo
41(82%)
40 (80%)
Cough
Vitamin A
25 (50%)
23 (46%)
P=0.345
Placebo
31 (62%)
31 (62%)
Loss of smell
and taste.
Vitamin A
23 (46%)
20 (40%)
P=0.47
Placebo
30 (60%)
30 (60%)
Table 2. SPO2 changes after 24 and 48 hours with vitamin A and placebo administration.
Variables
Mean before giving
Mean after 24 hr
Mean after 48 hr
Vitamin A administration
95.4%
97.17%
97.24%
Placebo administration
96.8%
94.42%
95.72%
P-value among mean SPO2 changes was =0.87
Table 3. Mean duration of symptoms among patients given vitamin A and placebo.
Variables
Mean duration of symptoms
Vitamin A administration
2.9
Placebo administration
4.64
Table 4. Number and percentage of patients who convert to the severe form.
Variable
Number of patients
Convert to severe disease
Percentage
Vitamin A administration
50
2
4%
Placebo administration
50
6
12%
P-value among deferent variables was <0.0001
Table 5. Incidence of getting infection and duration of symptoms among contacts in between that given vitamin A and placebo.
Variables
Number of contacts
Number and percentage of
getting the infection
Mean duration of symptoms to
infected patients
Vitamin A administration
97
20(20.62%)
4.6
Placebo administration
112
65(58.03%)
6.72
P-value among the incidence of the disease was <0.0001
... In a study of 100 COVID-19 patients with mild to moderate disease severity (50 patients on placebo and 50 on treatment), patients in the treatment group received 2 doses of vitamin A (200,000 IU) for 2 days. [22] The study showed that the symptoms of the patients in the treatment group decreased after 48 hours of supplementation, while the symptoms did not decrease in the placebo group. [22] Re-infection was seen in 20.62%, and 58.03% of the cases, while symptoms persisted for 4.6, and 6.72 days, respectively. ...
... [22] The study showed that the symptoms of the patients in the treatment group decreased after 48 hours of supplementation, while the symptoms did not decrease in the placebo group. [22] Re-infection was seen in 20.62%, and 58.03% of the cases, while symptoms persisted for 4.6, and 6.72 days, respectively. [22] In addition, in a clinical study (IRCT20210205050247N1) vitamin A was included in the treatment process of 90 patients to restore the loss of smell that occurs with the disease due to reduction in olfactory cells associated with vitamin A deficiency (https://www.irct.ir/trial/54178). ...
... [22] Re-infection was seen in 20.62%, and 58.03% of the cases, while symptoms persisted for 4.6, and 6.72 days, respectively. [22] In addition, in a clinical study (IRCT20210205050247N1) vitamin A was included in the treatment process of 90 patients to restore the loss of smell that occurs with the disease due to reduction in olfactory cells associated with vitamin A deficiency (https://www.irct.ir/trial/54178). Vitamin A given in pharmacological or high doses increased the formation of regulatory T cells while inhibiting the activity of T cells that might induce the development of the disease and the release of pro-inflammatory cytokines. ...
... Administration of vitamin A (200,000 I.U.), two doses for two days, showed a significant improvement in COVID-19 symptoms, duration of illness, deterioration rate compared with the control group [50]. Besides, the administration of vitamin A to contacts of COVID-19 patients also showed a beneficial effect related to the incidence of infection [50]. ...
... Administration of vitamin A (200,000 I.U.), two doses for two days, showed a significant improvement in COVID-19 symptoms, duration of illness, deterioration rate compared with the control group [50]. Besides, the administration of vitamin A to contacts of COVID-19 patients also showed a beneficial effect related to the incidence of infection [50]. ...
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