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Association of vitamin D deficiency with clinical presentation of COVID-19

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Background The coronavirus disease 2019 (COVID-19) is a respiratory virus, the spread of which has caused a global pandemic with catastrophic consequences. The current study aimed to investigate the association between vitamin D deficiency and the clinical presentation of COVID-19. Patients and methods The current study included 166 COVID-19 patients recruited from Prince Mohammad Bin Abdulaziz Hospital in Riyadh, Saudi Arabia. The study was conducted from October 2020 to January 2021. Patients were diagnosed by positive polymerase chain reaction (PCR) results. History and clinical data were collected for all subjects. In addition, laboratory analysis was done to estimate blood levels of 25 hydroxyvitamin D (25(OH)D), C-reactive protein (CRP), ferritin, parathyroid hormone (PTH), alanine aminotransferase (ALT), D-dimer, calcium, and relative lymphocytic count. COVID-19 patients were divided into three subgroups according to their vitamin D status. Patients were considered sufficient when their vitamin D level was above 30 ng/mL. Patients with vitamin D levels below 20 ng/mL were considered deficient. Patients with vitamin D levels ranging from 20 ng/mL to 30 ng/mL were considered insufficient. Results Our results showed that 81 patients (49%) were deficient in vitamin D, and 48 patients (29%) were insufficient in vitamin D. Only 37 patients (22%) had normal vitamin D levels. Moreover, a significant difference was found regarding the inflammatory markers of COVID-19 severity. Also, vitamin D levels were inversely correlated with the markers used for monitoring the condition of COVID-19 patients: ferritin, CRP, and D-dimer. Conclusion Our results showed that vitamin D deficiency was associated with increased levels of inflammatory markers of COVID-19 infection.
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Original Research Article
European Journal of Inammation
Volume 19: 110
© The Author(s) 2021
Article reuse guidelines:
sagepub.com/journals-permissions
DOI: 10.1177/20587392211038315
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Association of vitamin D deciency with
clinical presentation of COVID-19
Mazen Almehmadi
1
, Abdullah Turjoman
2
, Ahmad El-Askary
1
, Alaa Shae
1
,
Fatimah Rebh
2
, Muhannad Alenazi
1
, Mustafa Halawi
3
and Amal F. Gharib
1
Abstract
Background: The coronavirus disease 2019 (COVID-19) is a respiratory virus, the spread of which has caused a global
pandemic with catastrophic consequences. The current study aimed to investigate the association between vitamin D
deciency and the clinical presentation of COVID-19.
Patients and methods: The current study included 166 COVID-19 patients recruited from Prince Mohammad Bin
Abdulaziz Hospital in Riyadh, Saudi Arabia. The study was conducted from October 2020 to January 2021. Patients were
diagnosed by positive polymerase chain reaction (PCR) results. History and clinical data were collected for all subjects. In
addition, laboratory analysis was done to estimate blood levels of 25 hydroxyvitamin D (25(OH)D), C-reactive protein
(CRP), ferritin, parathyroid hormone (PTH), alanine aminotransferase (ALT), D-dimer, calcium, and relative lymphocytic
count. COVID-19 patients were divided into three subgroups according to their vitamin D status. Patients were considered
sufcient when their vitamin D level was above 30 ng/mL. Patients with vitamin D levels below 20 ng/mL were considered
decient. Patients with vitamin D levels ranging from 20 ng/mL to 30 ng/mL were considered insufcient.
Results: Our results showed that 81 patients (49%) were decient in vitamin D, and 48 patients (29%) were insufcient in
vitamin D. Only 37 patients (22%) had normal vitamin D levels. Moreover, a signicant difference was found regarding the
inammatory markers of COVID-19 severity. Also, vitamin D levels were inversely correlated with the markers used for
monitoring the condition of COVID-19 patients: ferritin, CRP, and D-dimer.
Conclusion: Our results showed that vitamin D deciency was associated with increased levels of inammatory markers
of COVID-19 infection.
Keywords
COVID-19, vitamin D, clinical presentation, inammatory markers
Date received: 26 March 2021; accepted: 15 July 2021
Introduction
The coronavirus infection has spread all over the world.
The outbreak started in Wuhan, Hubei, China, late in 2019
and was ofcially named COVID-19 by the World Health
Organization (WHO) on 11 February 2020.
1,2
This in-
fection is associated with severe acute respiratory syn-
drome coronavirus-2 (SARS-CoV-2) and threatens the
world.
3
There is variation in the clinical features of
COVID-19, as 17.9% of COVID-19 infections are mild,
while 15.7% of the patients developed severe illness after
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1
Department of Clinical Laboratory Sciences, College of Applied Medical
Sciences, Taif University, Taif, Saudi Arabia
2
Prince Mohammed Bin Abdulaziz Hospital, Riyadh, Saudi arabia
3
Department of Medical Laboratory Technology, College of Applied
Medical Sciences, Jazan University, Jazan, Saudi Arabia, Jazan, SA
Corresponding author:
Mazen Almehmadi, Department of Clinical Laboratory Sciences, College
of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif
21944, Saudi Arabia.
Email: Dr.mazen.ma@gmail.com,Mazenn@tu.edu.sa
being admitted to the hospital. On initial presentation, no
radiologic anomalies were found in 2.9% of patients with
serious disease.
4
COVID-19 shows its effect as initial immune suppres-
sion, followed by exaggerated immune system response,
resulting in a cytokine storm. COVID-19 can have severe
consequences, such as the development of acute respiratory
distress syndrome (ARDS) and systemic inammatory re-
sponse syndrome (SIRS).
5,6
Vitamin D deciency represents an important health
problem; more than one billion people are estimated to
have vitamin D deciency worldwide.
7,8
In Saudi Arabia,
the prevalence of vitamin D deciency is around 60%. Its
occurrence has been reported in different ages and both
genders.
9,10
Vitamin D exerts signicant antiviral and anti-inammatory
effects via its immunoregulatory actions as vitamin D receptors
have been recognized in many immunological cells, and certain
cells of the immune system can synthesize the active form of
vitamin D.
11
Vitamin D can reduce the risk of infection through several
effects: rst, it plays an antiviral role by enhancing antimi-
crobial peptides cathelicidin and B-defensin that diminish the
viral replication; second, enhancement of anti-inammatory
and diminishment of pro-inammatory cytokines (IL-6,
TNF-α,andIFN-γ) that cause pneumonia and lung insult.
2
The pro-inammatory cytokines are recognized as predictors
for bad outcomes in COVID-19 infection.
12
Previous research has reported that vitamin D deciency
may enhance the possibility of respiratory infections, in-
cluding respiratory syncytial virus, tuberculosis, and u. In
addition, it is considered a risk factor for ARDS.
13
The COVID-19 virus principally involves the pulmo-
nary type-II alveolar pneumocytes by binding to the in-
creased angiotensin-converting enzyme 2 receptors
(ACE2) of the infected person,
14
decreasing surfactant
production, and increasing surface tension, which results
from alveolar type-II pneumocytes dysfunction.
15
Vitamin
D metabolites can stimulate surfactant synthesis by mod-
ulating the renin-angiotensin system in alveolar type-II
cells protecting against acute lung injury.
16
Thus, vitamin
Ddeciency can be a pathogenic element in COVID-19.
Before the emergence of COVID-19 vaccines, vitamin D
supplementation and exposure to sunlight were included in
treatment protocols. In the current study, we aimed to dene
the prevalence and clinical signicance of vitamin D de-
ciency in hospitalized patients diagnosed with COVID-19.
Subjects and methods
Study design and participants
We planned a retrospective case control study including
166 patients with COVID-19, aged 2388 years, who were
admitted to the Prince Mohammad Bin Abdulaziz Hospital
in Riyadh, Saudi Arabia, between October 2020 and
January 2021. They were diagnosed by RT-PCR and
further assessment was done by computed tomography
(CT) scans of the chest.
Patients were further classied into three subgroups
according to their vitamin D status: a vitamin D sufcient
group (vitamin D > 30 ng/mL), a vitamin Ddecient group
(vitamin D < 20 ng/mL) and a vitamin Dinsufcient group
(vitamin D from 2030 ng/mL).
17
Specic criteria were
used to determine the number of cases to be recruited in the
study according Miaoulis and Michener.
18
For calculation
of the minimum sample size, the formula of Cochran
19
was
used, with condence value 95% at a signicant concen-
tration of 5%.
We have excluded patients with malabsorption diseases,
liver cirrhosis, and serum creatinine levels of > 2 mg/dL.
Patients who obtained oral vitamin D supplements or
previous anticonvulsant treatment were also excluded from
the study.
Data collection
Demographic and clinical data were collected from hospital
records of COVID-19 patients, stored in an electronic
database, and independently examined by two researchers.
Procedures were performed after prior approval by the
research ethics committee of Taif University (42-0010).
The outcome variable for COVID-19 severity was de-
ned as the combination of intensive care unit (ICU) ad-
mission, mechanical ventilation prerequisite, or in-hospital
mortality. Generally, the ICU admittance criteria were set
by following the rules by the American Thoracic Society
and the Infectious Diseases Society of America.
20
Laboratory measurements
Fasting venous blood samples were collected from
COVID-19 patients and allocated into two portions. The
sera were separated from the plain tubes for the estimation
of vitamin D, calcium, and the inammatory markers.
The whole blood from ethylenediaminetetraacetic acid
(EDTA)containing tubes were used for complete blood
count (CBC) tests. Serum 25(OH)D levels were determined
by using an Abcam human vitamin D enzyme-linked
immunosorbent assay (ELISA) kit, USA (Cat No.
ab213966), following the manufacturers protocol. The
range of detection was 0.51010 ng/mL, and the sensitivity
of the assay was 1.98 ng/mL. Serum vitamin D levels of
less than 20 ng/mL were considered decient. The PTH
serum levels were estimated by the Abcam Human PTH
ELISA kit, USA (Cat No. ab230931), based on the
company guidelines, with a detection range of 4.69
300 pg/mL and a sensitivity of 0.761 pg/mL.
2European Journal of Inammation
CRP was evaluated by using the immunoturbidimetric
method (CRP II Latex X2, Denka Seiken Co. Ltd., Tokyo,
Japan), utilizing an autoanalyzer (Toshiba, Tokyo, Japan).
The measurement range of this assay was 0.0132 mg/dL.
Serum ferritin levels were evaluated using an ELISA kit
(RCD012R, BioVendor) with an intra-assay CV of 7.3%
and an inter-assay CV of 4.5%. Serum D-dimer was mea-
sured by a human Abcam ELISA kit (Cat No. ab260076),
with a sensitivity of 2.36 ng/mL, intra-assay of 4.4%, and
inter-assay of 4.3%.
Serum calcium was estimated by a calcium colorimetric
assay kit, Abcam, USA (Cat No. ab102505), with a de-
tection range 0.4100 mg/dL, according to the manufac-
turers protocol.
Statistical analysis
Statistical Package for Social Sciences (SPSS) for Win-
dows version 20.0 (IBM SPSS Statistics, IBM Corporation,
Armonk, NY, USA) was used for data analysis. Data were
presented as mean ± standard deviation (SD) and one-way
analysis of variance (ANOVA), followed by Tukeys
honestly signicant difference (HSD). Post-hoc analyses
were used for multiple comparisons between groups. The
chi-square (x
2
) test of signicance was applied to compare
proportions, and the Pearson correlation coefcient was
used to assess the association between vitamin D and the
studied parameters. pvalues were considered statistically
signicant at < 0.05.
Results
For all COVID-19 patients, the mean age was (56 ± 16),
and sex distribution and laboratory characteristics are
shown in Table 1.
COVID-19 patients were divided into three subgroups
according to vitamin D levels. A signicant proportion
(49%) of COVID-19 patients (81 of 166) were decient in
vitamin D. About 48 patients (29%) were insufcient in
vitamin D. Only 37 patients (22%) had sufcient vitamin D
levels. Demographic data of the subgroups showed no
signicant difference regarding mean age of the vitamin D
decient group in comparison to the insufciency and
sufciency groups (61 ± 15 vs 56 ± 15 and 54 ± 16, re-
spectively). Regarding sex distribution, there was no statis-
tically signicant difference between three patient subgroups
(Table 2).
We reported a statistically high difference (pvalue <
0.001) when we compared the vitamin D deciency group
and both the insufciency and sufciency groups regarding
laboratory parameters: serum ferritin (890 ± 170 in the
deciency group versus 782 ± 188 in the insufciency
group and 678 ± 154 in the sufciency group), CRP (9 ± 4
in the deciency group versus 7 ± 3 in the insufciency
group and 6 ± 3 in the sufciency group), D-dimer (2.3 ±
1.1 in the deciency group versus 1.7 ± 0.8 in the insuf-
ciency group and 1.4 ± 0.4 in the sufciency group), PTH
(42 ± 7 in the deciency group versus 39 ± 8 in the in-
sufciency group and 36 ± 7 in the sufciency group),
calcium (7.9 ± 1.2 in the deciency group versus 8.2 ± 1.4
in the insufciency group versus 9.5 ± 0.8 in the sufciency
group), and vitamin D (14 ± 4 in the deciency group
versus 24 ± 2 in the insufciency group and 45 ± 15 in the
sufciency group). ALT and relative lymphocytic counts
showed no signicant difference between the three sub-
groups (Table 3).
The clinical features for each subgroup are represented
in Table 4. Only fever and fatigue showed signicant
differences between the three subgroups of patients (p
values were 0.01 and 0.003, respectively). The other pa-
rameters showed no statistically signicant differences
between the three subgroups (Table 4).
In the current study, we investigated the correlation
between vitamin D levels in COVID-19 patients and other
parameters of the patients included in the study. There was
a statistically signicant negative correlation between vi-
tamin D levels and ferritin, PTH, CRP, and D-dimer (p
values = 0.01, < 0.001, < 0.001, and 0.03, respectively) and
a signicant positive correlation with calcium (pvalues =
0.007). However, ALT, relative lymphocytic count, and age
showed no signicant correlation (Table 5). In addition, the
scatter plot curves for each signicant parameter correlated
with vitamin D levels were demonstrated in Figures 15.
Table 1. Demographic and laboratory characteristics of all
patients included in the study.
Parameter Patients (n= 166)
Age (years)
(Mean ± SD) 56 ± 16
Sex
Female (n, %) 58 (35%)
Male (n, %) 108 (65%)
Ferritin (ng/mL)
(Mean ± SD) 790 ± 670
ALT (U/L)
(Mean ± SD) 140 ± 106
PTH (pg/mL)
(Mean ± SD) 38 ± 10
Lymphocytes (%) 8.0 ± 2.0
Calcium (mg/dL)
(Mean ± SD) 8.0 ± 1.0
CRP (mg/L)
(Mean ± SD) 7.0 ± 6.0
D-dimer (ng/mL)
(Mean ± SD) 2.0 ± 3.0
Vitamin D (ng/mL)
(Mean ± SD) 23 ± 15
Data are presented as mean ± SD, number, and (%).
Almehmadi et al. 3
Discussion
The current study was conducted to evaluate the vitamin D
status among COVID-19 patients and to study the asso-
ciation of vitamin D deciency with clinical data and in-
ammatory biomarkers in COVID-19 patients.
Although little is known about the effects of vitamin D
deciency on the clinical presentation and the outcome of
COVID-19 infection,
21
several studies have demonstrated
the relationship between other respiratory infections and
vitamin D. Vitamin D has been reported to protect against
respiratory infections.
2224
Table 2. Comparison between subgroups of COVID-19 patients according to demographic data.
Parameter Deciency (n= 81) Insufciency (n= 48) Sufciency (n= 37) p-value
Age (years)
Mean ± SD 61 ± 15 56 ± 15 54 ± 16 0.06
Sex
Female 24 (30%) 15 (31%) 19 (51%)
Male 57 (70%) 33 (69%) 18 (49%) 0.06
Data are presented as mean using F-one-way analysis of variance.
Data are presented as number and (%) using the chi-square test.
**p-value < 0.001 HS; *p-value < 0.05 S.
Table 3. Comparison between COVID-19 patients subgroups according to laboratory data.
Laboratory data Deciency (n = 81) Insufciency (n = 48) Sufciency (n = 37) p-value
Ferritin (ng/ml) 890 ± 170 782 ± 188a 678 ± 154ab < 0.001**
ALT (U/L) 132 ± 95 139 ± 108 160 ± 124 0.38
PTH (pg/mL) 42 ± 7 39 ± 8a 36 ± 7ab < 0.001**
Relative lymphocytes (%) 7 ± 3 8 ± 2 8 ± 2 0.08
Calcium (mg/dL) 7.9 ± 1.2 8.2 ± 1.4a 9.5 ± 0.8ab < 0.001**
CRP (mg/L) 9 ± 4 7 ± 3a 6 ± 3ab < 0.001**
D-dimer (ng/mL) 2.3 ± 1.1 1.7 ± 0.8a 1.4 ± 0.4ab < 0.001**
Vitamin D 14 ± 4 24 ± 2a 45 ± 15ab < 0.001**
Using: F-one-way analysis of variance.
Post-hoc test, LSD: a: statistically signicant difference with the deciency group; b: statistically signicant difference with insufciency group.
p-value > 0.05 NS; *p-value < 0.05 S; **p-value < 0.001 HS.
Table 4. Clinical characteristics of COVID-19 patients in the three subgroups.
Deciency (n= 81) Insufciency (n= 48) Sufciency (n= 37) p-value
Fever 73 38 25 0.01*
Cough 45 28 22 0.91
Headache 29 19 16 0.73
Fatigue 61 36 17 0.003*
Anosmia 45 35 27 0.06
Loss of taste 44 33 25 0.18
Diarrhea 32 21 16 0.86
Diabetes mellitus 19 13 5 0.31
Hypertension 17 11 4 0.32
ICU admission 7 3 1 0.48
CPAP 5 2 1 0.69
Mechanical ventilation 2 1 0 0.64
Mortality 2 1 0 0.64
Data are presented as number using the chi-square test.
Abbreviation: CPAP: continuous positive airway pressure.
*p-value < 0.05 S; p-value > 0.05 NS.
4European Journal of Inammation
In our current research, we found that 49% of COVID-
19 patients enrolled in the study were decient in vitamin
D, while 29% were insufcient in vitamin D, resulting in a
total of 78% with deciency or insufciency in vitamin D.
Also, we found that the vitamin D deciency group in-
cluded elderly patients.
In accordance with our ndings, Zhou et al.
25
revealed
that patients with a serum vitamin D level of less than
20 ng/mL had a 64% higher chance of getting community-
acquired pneumonia. Ricci et al.
26
reported that 80% of
their COVID-19 patients had vitamin D deciency and
6.5% had vitamin D insufciency. Paiz et al.
27
reported that
vitamin D has recently become more prominent in studies
due to its possible effect on the incidence of COVID-19
infection. Moreover, Ilie et al.
22
found that the oldest
portion of the population, which is the most susceptible to
COVID-19 infection, is also the group with the lowest
vitamin D levels. On the other hand, Ali,
28
revealed that
there is insufcient evidence to link vitamin D levels with
COVID-19 severity and mortality.
The current study evaluated the effect of vitamin D
deciency on the inammatory markers that are used to
assess the clinical conditions of patients, such as serum
ferritin, CRP, ALT, and D-dimer. We observed higher
concentrations of inammatory markers in the vitamin
Ddeciency group when compared to the other two
groups.
Our ndings agree with a previous study by Yilmaz and
S
¸en,
29
which found that vitamin D may reduce the incidence
of inammatory markers, which are effective predictors of
worse outcomes in children with COVID-19 infection. The
pathology of COVID-19 includes a complex interaction
between the virus and the host immune system. COVID-19
triggers the release of pro-inammatory cytokines. Vitamin
D has been reported as a modulator of the immune re-
sponse of macrophages, preventing them from releasing
several inammatory cytokines and chemokines.
12,30
Table 5. Correlation between vitamin D with all parameters in
COVID-19 patients group.
Parameter
Vitamin D
Rp-value
Age (years) 0.13 0.09
Ferritin (ng/ml) 0.44 0.01*
ALT (U/L) 0.07 0.34
PTH (pg/mL) 0.60 < 0.001**
Lymphocytes (%) 0.14 0.07
Calcium (mg/mL) 0.5 0.007*
CRP (mg/L) 0.6 < 0.001**
D-dimer (ng/mL) 0.36 0.03*
Using r-Pearson correlation coefcient.
p-value > 0.05 NS; *p-value < 0.05 S; **p-value < 0.001 HS.
Figure 1. Scatter plot between Vitamin D with ferritin in patients group. r = 0.44; p= 0.01.
Almehmadi et al. 5
Figure 2. Scatter plot between Vitamin D with PTH in patients group. r = 0.60; p< 0.001.
Figure 3. Scatter plot between Vitamin D with D-dimer in patients group. r = 0.36, p= 0.03.
6European Journal of Inammation
Figure 4. Scatter plot between Vitamin D with CRP in patients group. r = 0.6, p< 0.001.
Figure 5. Scatter plot between Vitamin D with calcium in patients group. r = 0.5, p= 0.007.
Almehmadi et al. 7
In our current research, we studied the correlation be-
tween vitamin D and inammatory markers used in clinical
practice to assess the severity of COVID-19. Signicant
negative correlations were reported between lower vitamin
D levels and higher inammatory markers CRP, ferritin,
and D-dimer. In accordance with our ndings, Daneshkhah
et al.
31
observed that high CRP was inversely correlated
with vitamin D levels. Our results suggest a possible role
for vitamin D in the reduction of complications caused by
the cytokine storm, considering C-reactive protein as an
important marker for the severity of COVID-19 inam-
mation and the cytokine storm. Moreover, Ricci et al.
26
found a signicant relation between high levels of D-dimer
and low levels of vitamin D.
The relationship between vitamin D and inammatory
diseases has triggered a lot of debate because the mech-
anism of the link between low vitamin D concentrations
and increased inammatory cytokines levels has not been
completely explored. A recent meta-analysis conducted by
Kazemi et al.
32
discovered that in COVID-19, the associ-
ation between vitamin D deciency and lung inammation
was contradictory and the relationship between vitamin D
deciency and mortality was ambiguous. Vitamin D de-
ciency is prevalent in hospitalized patients with severe
illnesses, especially in those who are critically ill.
3335
There are several conicting results at this point.
Yousefzadeh et al.
36
reported that vitamin D levels mea-
sured during an acute disease may be an inaccurate
biomarker of vitamin D status, and the changes in vitamin
Dbinding protein (DBP) levels should be noted as con-
founding factors when interpreting 25(OH)D concentra-
tions in blood. Another explanation by Quraishi and
Camargo
37
is that lower 25(OH)D levels can be caused by
lower levels of DBP due to interstitial leakage caused by
increased vascular permeability during inammatory dis-
eases. Amrein et al.
38
revealed that vitamin D levels as-
sessed at the beginning of an acute inammatory injury can
represent the acute phase of the illness rather than true
vitamin D levels. Moreover, Waldron et al.
39
suggested that
serum 25(OH)D is a negative acute phase reactant, and
after an acute inammatory injury, serum 25(OH)D is an
ineffective biomarker of vitamin D status.
On the other hand, vitamin D regulates immune reac-
tions induced by macrophages and dendritic cells, which
are the rst line of host defense, preventing them from the
production of excessive inammatory cytokine and che-
mokine.
40
The value of vitamin D sufciency in serious
disease is strongly supported by the study of Braun et al.,
41
in which 25(OH)D was measured at the start of critical
treatment. Mata-Granados et al.
42
observed that large doses
of oral 25(OH)D can correct vitamin D deciency and
could lead to improvement in general health and most
likely, a decrease in the overall mortality rate of critically ill
patients.
Regarding the clinical presentations of the COVID-19
patients we studied, the clinical features of COVID-19
infection were more prominent among the vitamin D
decient group in comparison to other groups. Patients
who were decient in vitamin D had a higher frequency of
fever and fatigue in comparison to the other groups, and the
difference was statistically signicant. In consistency with
our results, Mardani et al.
43
observed that adequate vitamin
D may have a controlling effect on the symptoms of
COVID-19 infection by interfering with the rennin-
angiotensin-aldosterone system (RAAS) and immune sys-
tem functions through the vitamin D receptor (VDR), which
is a ligand-activated transcription factor. Pereira et al.
44
observed a positive association between vitamin D de-
ciency and the severity of the disease. Moreover, Ilie et al.
22
found a signicant relation between vitamin D levels and the
number of COVID-19 cases in different European countries,
with increased mortality.
Considering the causes of clinical diversity in the course
and mortality rates of COVID-19 cases, it is necessary to
point out that vitamin D deciency may also underlie the
comorbidity of patients.
45
This study has limitations. The retrospective design of
the study may possibly involve incomplete or incorrect
data, and the number of patients in the study may be small,
but it may provide guidance which helps researchers
perform larger studies to explore the effects of vitamin D
deciency on COVID-19 infected patients. The study was
underpowered to examine severity due to the small
numbers of mortality and ICU-admitted patients. In ad-
dition, vitamin D levels before the start of COVID-19
infection were not reported for included patients. So, vi-
tamin D levels should be measured before and at the onset
of acute diseases in future research, with adjustment for all
possible affecting factors such as age, sex, BMI, diet,
medication, vitamin D supplementation, and socioeco-
nomic factors.
Conclusion
We evaluated vitamin D status and its relationship with
clinical features in hospitalized patients with COVID-19.
Our results suggested that vitamin D deciency was as-
sociated with increased levels of inammatory markers of
COVID-19 infection.
Acknowledgments
The authors would like to thank Taif University, Taif, Saudi Arabia,
for their support (Taif University Researchers Supporting Project
number: TURSP-2020/80), Taif University, Taif, Saudi Arabia.
8European Journal of Inammation
Declaration of conicting interests
The author(s) declared no potential conicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The author(s) disclosed receipt of the following nancial support
for the research, authorship, and/or publication of this article: The
work was funded by Taif University, Taif, Saudi Arabia. (Taif
University Researchers Supporting Project number: TURSP-
2020/80).
ORCID iD
Mazen Almehmadi https://orcid.org/0000-0002-7580-8667
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10 European Journal of Inammation
... [9] It has been suggested that adequate vitamin D levels can prevent cytokine storms and reduce the severity of the disease by regulating inflammatory marker levels in COVID-19 patients. [10] It has been observed that the serum vitamin D level is lower in COVID-19 positive patients than in negative patients. [10,11] Studies in different European countries [12][13][14] show that there is a relationship between the increasing number of COVID-19 cases, mortality and severity and vitamin D deficiency. ...
... [10] It has been observed that the serum vitamin D level is lower in COVID-19 positive patients than in negative patients. [10,11] Studies in different European countries [12][13][14] show that there is a relationship between the increasing number of COVID-19 cases, mortality and severity and vitamin D deficiency. In contrast, Chen et al. [15] showed that vitamin D deficiency or insufficiency, even vitamin D supplementation was not significant in the risk of COVID-19 or susceptibility to death in a meta-analysis study involving 536,105 patients. ...
... [19] It has been reported that COVID-19 positive patients with serum vitamin D level >30 ng/ml have very low CRP levels moreover, vitamin D levels and ferritin, CRP and D dimer levels are inversely proportional. [10] In addition, it was found that vitamin D level was positively correlated with lymphocyte count and negatively correlated with CRP and fibrinogen levels in pediatric COVID-19 cases. [28] Compared to COVID-19 negative groups, COVID-19 patients were found to have higher levels of HCT, neutrophils and CRP but lower levels of Hb, monocytes, eosinophils and basophils. ...
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Amaç :Although some recent studies have shown that serum 25-hydroxyvitamin D (25(OH)D) may be effective on the course of Covid-19 disease, the results obtained are still controversial. Therefore, in this study, it was aimed to examine whether there are differences in terms of age, gender, length of hospital stay, biochemical and hematological parameters between those with and without serum 25(OH)D deficiency in Covid-19 patients. Gereç ve Yöntem: The data of 413 patients hospitalized in Ankara Pursaklar State Hospital whose covid-19 positivity was revealed by PCR test were evaluated retrospectively. Those with less than serum 25(OH)D (
... It is caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in Wuhan, China, and was transmitted to other parts of the world. The WHO declared that COVID-19 as a novel pandemic on February 11, 2020, with variation in clinical characteristics, including 15.7 % patients had a severe illness, and 17.9 % infections were mild (Almehmadi et al., 2021). COVID-19 exhibits an early immune suppression, followed by an anomalously activated immune response, including the cytokine storm. ...
... COVID-19 exhibits an early immune suppression, followed by an anomalously activated immune response, including the cytokine storm. The infection triggers severe consequences, including systemic inflammatory response syndrome and acute respiratory distress syndrome (Almehmadi et al., 2021). All infection incidents, recent epidemics, and the COVID-19 pandemic confirm that CoVs threaten humans and the economy continuously since they spread easily, emerge unexpectedly, and cause catastrophic consequences. ...
... VD deficiency is an important health problem that increases people's vulnerability to coronavirus infections, including COVID-19. Approximately one billion people have VD deficiency globally (Almehmadi et al., 2021;Nimavat et al., 2021). In winter, incidents of influenza increase due to decreased access to vitamin D via sunlight. ...
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Coronaviruses, especially Beta coronaviruses (β)is a threat to humans since it spreads easily. Although we are yet to find a cure to COVID-19, there are various approaches to prevent its spread, including UV and heat inactivation. However, recently scholars have identified an increased relationship between vitamin D-deficiency and the severe COVID-19, making it a feasible intervention to treat or prevent COVID-19. We can obtain vitamin D directly through sunlight, diet, or supplementation. Vitamin D, especially vitamin D2 and D3 prevents COVID-19 by enhancing anti-inflammatory and eradicating pro-inflammatory cytokines and acting as an antiviral by augmenting B-defensin and antimicrobial peptides cathelicidin, declining viral replication. People with vitamin D deficiency are more susceptible to SARS-CoV-2 than normal peopole. Vitamin D is safe and has limited adverse events because although it is a fat-soluble vitamin, humans rarely experience vitamin D overdose, including vitamin D overdoses due to sunlight.
... In addition, the relation between low levels of serum 25 (OH)D and elevated serum transaminases was revealed in several studies previously [24,25]. Nevertheless, Almehmadi et al. did not find any association between Vitamin-D and ALT in COVID-19 patients [26]. There was no association between vitamin-D and AST and ALT in COVID-19 patients in another study [27]. ...
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Background The benefits and harms of vitamin D supplementation in the treatment of COVID-19 have not yet been fully documented. In this study, we aimed to evaluate the effects of high-dose vitamin D supplementation on liver function tests in COVID-19. Method This double-blinded randomized clinical trial was conducted on 140 hospitalized patients aged > 30 years. Patients were randomly allocated to receive either intervention group (n = 70 receiving 50,000 IU of vitamin D capsules orally as a single dose and then 10,000 IU syrup daily from the second day of admission for 30 days) and the control group (n = 70 receiving 1000 IU vitamin D syrup orally per day). Liver function tests (LFT), including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and Lactate Dehydrogenase (LDH) were evaluated at baseline and at the end of the intervention. Decision tree analysis was performed to identify the predictors for change in liver enzymes. Results Among COVID-19 patients, a significant decrease was observed in serum level of ALP between intervention and placebo groups (p = 0.04). In addition, decision tree analysis revealed that GGT, temperature, serum magnesium level at baseline and gender were the most important predictors of ALT changes in COVID-19 patients. Conclusion High-dose vitamin D supplementation improved ALP markers among COVID-19 patients. More randomized controlled trials with longer follow-up times will be required.
... Our study is in concur with Mazen Almehmadi1 et al. [13]. Their results showed that vitamin D levels were inversely correlated with the markers used for monitoring the condition of COVID-19 patients: ferritin, CRP, and D-dimer, and serum vitamin D was low in symptomatic patients and normal in non-symptomatic patients. ...
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The outbreak of coronavirus disease 2019 (COVID-19), which is caused by the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was announced a pandemic in March 2020 by the World Health Organization. The disease can be diagnosed on the basis of clinical symptoms, polymerase chain reaction positivity, and the presence of ground-glass opacities on computed tomography (CT) scans. Recent studies have focused on the role of serum inflammatory markers that predict COVID-19, such as lymphocyte counts and C-reactive protein (CRP), homocysteine, and D-dimer levels. Vitamin D is thought to reduce the risk of viral infections through several mechanisms. Our aim was to evaluate the correlation between serum vitamin D level and inflammatory markers and severity in Egyptian patients with COVID-19 infection. Serum vitamin D level had a positive correlation with hemoglobin level and lymphocytes. As results, serum vitamin D had a negative correlation with serum ferritin, CRP, and D-dimer and was not correlated with CORAD scoring in the CT chest. In conclusion, serum vitamin D was inversely correlated with inflammatory markers (ferritin, CRP, and D-dimer) which mean that participants with symptoms of COVID-19 had a high level of inflammatory markers and a low level of vitamin D. Participants without symptoms of COVID-19 had normal inflammatory markers and normal vitamin D level.
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Purpose of Review In the midst of the COVID-19 pandemic, several academic studies have emerged that explore the importance of vitamin D in the development of the SARS-CoV2 infection. The basis of this interest comes from the established effect vitamin D status has on other acute respiratory infections, such as influenza. This article aims to determine the role and effect of vitamin D serum concentration in the prevalence and severity of COVID-19. Recent Findings Several observational studies have demonstrated that suboptimal levels of vitamin D serum concentrations can significantly increase the risk of developing COVID-19 and lead to a more severe symptomatology. One study suggests, however, that supplementation of vitamin D could potentially increase the incidence of mortality in COVID-19 patients. Summary Vitamin D status could have an influential role in the development and progression of SARS-CoV2 infection. Further studies are warranted to understand fully the veracity and the extent of this association.
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ABSTRACT This systematic review was conducted to summarize and clarify the evidence on the association between 25-hydroxyvitamin-D [25(OH)D] concentrations and coronavirus disease 2019 (COVID-19) risk and outcomes. PubMed, Scopus, and Web of Science databases and Google Scholar were searched up to 26 November 2020. All retrospective and prospective cohort, cross-sectional, case-control, and randomized controlled trial studies that investigated the relation between 25(OH)D and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 severity were included. Thirty-nine studies were included in the current systematic review. In studies that were adjusted (OR: 1.77; 95% CI: 1.24, 2.53; I2: 44.2%) and nonadjusted for confounders (OR: 1.75; 95% CI: 1.44, 2.13; I2: 33.0%) there was a higher risk of SARS-CoV-2 infection in the vitamin D deficiency (VDD) group. Fifteen studies evaluated associations between VDD and composite severity. In the studies that were adjusted (OR: 2.57; 95% CI: 1.65, 4.01; I2 = 0.0%) and nonadjusted for confounders (OR: 10.61; 95% CI: 2.07, 54.23; I2 = 90.8%) there was a higher severity in the VDD group. Analysis of studies with crude OR (OR: 2.62; 95% CI: 1.13, 6.05; I2: 47.9%), and adjusted studies that used the Cox survival method (HR: 2.35; 95% CI: 1.22, 4.52; I2: 84%) indicated a significant association of VDD with mortality, while in adjusted studies that used logistic regression, no relation was observed (OR: 1.05; 95% CI: 0.63, 1.75; I2: 76.6%). The results of studies that examined relations between VDD and intensive care unit (ICU) admission, pulmonary complications, hospitalization, and inflammation were inconsistent. In conclusion, although studies were heterogeneous in methodological and statistical approach, most of them indicated a significant relation between 25(OH)D and SARS-CoV-2 infection, COVID-19 composite severity, and mortality. With regard to infection, caution should be taken in interpreting the results, due to inherent study limitations. For ICU admission, inflammation, hospitalization, and pulmonary involvement, the evidence is currently inconsistent and insufficient.
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Background Several immune mechanisms activate in COVID-19 pathogenesis. Usually, coronavirus infection is characterized by dysregulated host immune responses, interleukine-6 increase, hyper-activation of cytotoxic CD8 T lymphocytes. Interestingly, Vitamin D deficiency has been often associated with altered immune responses and infections. In the present study, we evaluated Vitamin D plasma levels in patients affected with different lung involvement during COVID-19 infection. Methods Lymphocyte phenotypes were assessed by flow cytometry. Thoracic CT scan involvement was obtained by an image analysis program. Results Vitamin D levels were deficient in (80%) of patients, insufficient in (6.5%) and normal in (13.5%). Patients with very low Vitamin D plasma levels had more elevated D-Dimer values, a more elevated B lymphocyte cell count, a reduction of CD8 + T lymphocytes with a low CD4/CD8 ratio, more compromised clinical findings (measured by LIPI and SOFA scores) and thoracic CT scan involvement. Conclusions Vitamin D deficiency is associated with compromised inflammatory responses and higher pulmonary involvement in COVID-19 affected patients. Vitamin D assessment, during COVID-19 infection, could be a useful analysis for possible therapeutic interventions. Trial registration: 'retrospectively registered'.
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The world is now experiencing its third major epidemic of coronavirus (CoV) infections began in Wuhan, Hubei, China, in late 2019 and named COVID-19. After an initial explosive outbreak of pneumonia of unknown etiology in China, the disease spread first to neighboring Asian countries and then worldwide. Patients with COVID-19 presented with a constellation of symptoms such as fever, dry cough, dyspnea, sore throat, and nasal congestion and radiological findings showed bilateral lung glassy opacities. Vitamin D has many mechanisms by which it reduces the risk of microbial infection and death, including physical barrier, cellular natural immunity, and adaptive immunity. Vitamin D supplementation has shown favorable effects in viral infections including influenza and HIV. The effects of vitamin D supplementation during covid 19 infection remain controversial. Looking ahead, clinical studies are needed to define better cut offs for vitamin D levels and, finally, which dosage is the best.
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There is still limited evidence regarding the influence of vitamin D in people with COVID-19. In this systematic review and meta-analysis, we analyze the association between vitamin D deficiency and COVID-19 severity, via an analysis of the prevalence of vitamin D deficiency and insufficiency in people with the disease. Five online databases-Embase, PubMed, Scopus, Web of Science, ScienceDirect and pre-print Medrevix were searched. The inclusion criteria were observational studies measuring serum vitamin D in adult and elderly subjects with COVID-19. The main outcome was the prevalence of vitamin D deficiency in severe cases of COVID-19. We carried out a meta-analysis with random effect measures. We identified 1542 articles and selected 27. Vitamin D deficiency was not associated with a higher chance of infection by COVID-19 (OR = 1.35; 95%CI = 0.80-1.88), but we identified that severe cases of COVID-19 present 64% (OR = 1.64; 95%CI = 1.30-2.09) more vitamin D deficiency compared with mild cases. A vitamin D concentration insufficiency increased hospitalization (OR = 1.81, 95%CI = 1.41-2.21) and mortality from COVID-19 (OR = 1.82, 95%CI = 1.06-2.58). We observed a positive association between vitamin D deficiency and the severity of the disease.
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Objective Coronavirus disease 2019 (COVID‐19) is a global health problem that can result in serious complications. The aim of this study was to investigate the prevalence and clinical importance of vitamin D deficiency in children with COVID‐19. Material and Methods This study includes 40 patients who were diagnosed to have COVID‐19 and hospitalized with the real‐time reverse transcription polymerase chain reaction method, 45 healthy matched control subjects with vitamin D levels. The age of admission, clinical and laboratory data, and 25‐hydroxycholecalciferol (25‐OHD) levels were recorded. Those with vitamin D levels which are below 20 ng/ml were determined as Group 1 and those with ≥20 ng/ml as Group 2. Results Patients with COVID‐19 had significantly lower vitamin D levels 13.14 μg/L (4.19–69.28) than did the controls 34.81 (3.8–77.42) μg/L (p < .001). Patients with COVID‐19 also had significantly lower serum phosphorus (4.09 ± 0.73 vs. 5.06 ± 0.93 vs. (U/L) (p < .001)) values compared with the controls. The symptom of fever was significantly higher in COVID‐ 19 patients who had deficient and insufficient vitamin D levels than in patients who had sufficient vitamin D levels (p = .038). There was a negative correlation found between fever symptom and vitamin D level (r = −0.358, p = .023). Conclusion This is the first to evaluate vitamin D levels and its relationship with clinical findings in pediatric patients with COVID‐19. Our results suggest that vitamin D values may be associated with the occurrence and management of the COVID‐19 disease by modulating the immunological mechanism to the virus in the pediatric population.
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Objectives: We present evidence for a possible role of Vitamin D (VitD) deficiency in unregulated cytokine production and inflammation leading to complications in COVID-19 patients. Design: The time-adjusted case mortality ratio (T-CMR) was estimated as the ratio of deceased patients on day N to the confirmed cases on day N-8. The adaptive average of T-CMR (A-CMR) was calculated as a metric of COVID-19 associated mortality. A model based on positivity change (PC) and an estimated prevalence of COVID-19 was used to determine countries with similar screening strategies. A possible association of A-CMR with the mean concentration of 25-hydroxyvitamin D (25(OH)D) in elderly individuals in countries with similar screening strategy was investigated. We considered high C-reactive protein (CRP) in severe COVID-19 patients (CRP ≥ 1 mg/dL) as a surrogate of a cytokine storm. We considered high-sensitivity CRP (hs-CRP) in healthy subjects as hs-CRP ≥ 0.2 mg/dL. Results: A link between 25(OH)D and A-CMR in countries with similar screening strategy is evidence for VitD's possible role in reducing unregulated cytokine production and inflammation among patients with severe COVID-19. We observed an odds ratio (OR) of 1.8 with 95% confidence interval (95% CI) (1.2 to 2.6) and an OR of 1.9 with 95% CI (1.4 to 2.7) for hs-CRP in VitD deficient elderly from low-income families and high-income families, respectively. COVID-19 patient-level data show an OR of 3.4 with 95% CI (2.15 to 5.4) for high CRP in severe COVID-19 patients. Conclusion: We conclude that future studies on VitD's role in reducing cytokine storm and COVID-19 mortality are warranted.
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The outbreak of COVID-19 has created a global public health crisis. Little is known about the protective factors of this infection. Therefore, preventive health measures that can reduce the risk of infection, progression and severity are desperately needed. This review discussed the possible roles of vitamin D in reducing the risk of COVID-19 and other acute respiratory tract infections and severity. Moreover, this study determined the correlation of vitamin D levels with COVID-19 cases and deaths in 20 European countries as of 20 May 2020. A significant negative correlation (p = 0.033) has been observed between mean vitamin D levels and COVID-19 cases per one million population in European countries. However, the correlation of vitamin D with COVID-19 deaths of these countries was not significant. Some retrospective studies demonstrated a correlation between vitamin D status and COVID-19 severity and mortality, while other studies did not find the correlation when confounding variables are adjusted. Several studies demonstrated the role of vitamin D in reducing the risk of acute viral respiratory tract infections and pneumonia. These include direct inhibition with viral replication or with anti-inflammatory or immunomodulatory ways. In the meta-analysis, vitamin D supplementation has been shown as safe and effective against acute respiratory tract infections. Thus, people who are at higher risk of vitamin D deficiency during this global pandemic should consider taking vitamin D supplements to maintain the circulating 25(OH)D in the optimal levels 75-125 nmol/L. In conclusion, there not enough evidence on the association between vitamin D levels and COVID-19 severity and mortality. Therefore, randomized control trials and cohort studies are necessary to test this hypothesis.
Article
In late 2019, SARS-CoV-2 started to spread throughout the world causing the COVID-19 that has taken a considerable number of lives. Results obtained from several investigations have explained the virus origin, pathogenicity, and transmission. Similar to SARS coronavirus, the pulmonary angiotensin converting enzyme (ACE) 2 was introduced as the virus receptor for entering the cell. An increased body of epidemiological and clinical evidences has shown modulating effects of vitamin D in lung injuries through several mechanisms. Several clinical symptoms as well as molecular factors have shown to be related to the disease transmission and severity. In this study, vitamin D, ACE concentrations, and neutrophil to lymphocyte ratio (NLR) were measured in patients with confirmed COVID-19 in comparison with control group. Results demonstrated significant alterations in vitamin D and ACE levels as well as NLR in the patients’ group. Contribution of those factors with the prognosis and severity of the disease has been shown.