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

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 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.

Full text

Original Research Article
European Journal of Inflammation
Volume 19: 1–10
© The Author(s) 2021
Article reuse guidelines:
sagepub.com/journals-permissions
DOI: 10.1177/20587392211038315
journals.sagepub.com/home/eji
Association of vitamin D deficiency with
clinical presentation of COVID-19
Mazen Almehmadi
1
, Abdullah Turjoman
2
, Ahmad El-Askary
1
, Alaa Shafie
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
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.
Keywords
COVID-19, vitamin D, clinical presentation, inflammatory 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 officially 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 inflammatory re-
sponse syndrome (SIRS).
5,6
Vitamin D deficiency represents an important health
problem; more than one billion people are estimated to
have vitamin D deficiency worldwide.
7,8
In Saudi Arabia,
the prevalence of vitamin D deficiency is around 60%. Its
occurrence has been reported in different ages and both
genders.
9,10
Vitamin D exerts significant antiviral and anti-inflammatory
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: first, it plays an antiviral role by enhancing antimi-
crobial peptides cathelicidin and B-defensin that diminish the
viral replication; second, enhancement of anti-inflammatory
and diminishment of pro-inflammatory cytokines (IL-6,
TNF-α,andIFN-γ) that cause pneumonia and lung insult.
2
The pro-inflammatory cytokines are recognized as predictors
for bad outcomes in COVID-19 infection.
12
Previous research has reported that vitamin D deficiency
may enhance the possibility of respiratory infections, in-
cluding respiratory syncytial virus, tuberculosis, and flu. 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
Ddeficiency 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 define
the prevalence and clinical significance of vitamin D de-
ficiency 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 23–88 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 classified into three subgroups
according to their vitamin D status: a vitamin D sufficient
group (vitamin D > 30 ng/mL), a vitamin D–deficient group
(vitamin D < 20 ng/mL) and a vitamin D–insufficient group
(vitamin D from 20–30 ng/mL).
17
Specific 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 confidence value 95% at a significant 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-
fined 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 inflammatory 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 manufacturer’s protocol. The
range of detection was 0.5–1010 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 deficient. 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 Inflammation

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 0.01–32 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 0.4–100 mg/dL, according to the manufac-
turer’s 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 Tukey’s
honestly significant difference (HSD). Post-hoc analyses
were used for multiple comparisons between groups. The
chi-square (x
2
) test of significance was applied to compare
proportions, and the Pearson correlation coefficient was
used to assess the association between vitamin D and the
studied parameters. pvalues were considered statistically
significant 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 significant proportion
(49%) of COVID-19 patients (81 of 166) were deficient in
vitamin D. About 48 patients (29%) were insufficient in
vitamin D. Only 37 patients (22%) had sufficient vitamin D
levels. Demographic data of the subgroups showed no
significant difference regarding mean age of the vitamin D–
deficient group in comparison to the insufficiency and
sufficiency groups (61 ± 15 vs 56 ± 15 and 54 ± 16, re-
spectively). Regarding sex distribution, there was no statis-
tically significant difference between three patient subgroups
(Table 2).
We reported a statistically high difference (pvalue <
0.001) when we compared the vitamin D deficiency group
and both the insufficiency and sufficiency groups regarding
laboratory parameters: serum ferritin (890 ± 170 in the
deficiency group versus 782 ± 188 in the insufficiency
group and 678 ± 154 in the sufficiency group), CRP (9 ± 4
in the deficiency group versus 7 ± 3 in the insufficiency
group and 6 ± 3 in the sufficiency group), D-dimer (2.3 ±
1.1 in the deficiency group versus 1.7 ± 0.8 in the insuf-
ficiency group and 1.4 ± 0.4 in the sufficiency group), PTH
(42 ± 7 in the deficiency group versus 39 ± 8 in the in-
sufficiency group and 36 ± 7 in the sufficiency group),
calcium (7.9 ± 1.2 in the deficiency group versus 8.2 ± 1.4
in the insufficiency group versus 9.5 ± 0.8 in the sufficiency
group), and vitamin D (14 ± 4 in the deficiency group
versus 24 ± 2 in the insufficiency group and 45 ± 15 in the
sufficiency group). ALT and relative lymphocytic counts
showed no significant difference between the three sub-
groups (Table 3).
The clinical features for each subgroup are represented
in Table 4. Only fever and fatigue showed significant
differences between the three subgroups of patients (p
values were 0.01 and 0.003, respectively). The other pa-
rameters showed no statistically significant 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 significant 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 significant positive correlation with calcium (pvalues =
0.007). However, ALT, relative lymphocytic count, and age
showed no significant correlation (Table 5). In addition, the
scatter plot curves for each significant parameter correlated
with vitamin D levels were demonstrated in Figures 1–5.
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 deficiency with clinical data and in-
flammatory biomarkers in COVID-19 patients.
Although little is known about the effects of vitamin D
deficiency 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.
22–24
Table 2. Comparison between subgroups of COVID-19 patients according to demographic data.
Parameter Deficiency (n= 81) Insufficiency (n= 48) Sufficiency (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 Deficiency (n = 81) Insufficiency (n = 48) Sufficiency (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 significant difference with the deficiency group; b: statistically significant difference with insufficiency 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.
Deficiency (n= 81) Insufficiency (n= 48) Sufficiency (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 Inflammation

In our current research, we found that 49% of COVID-
19 patients enrolled in the study were deficient in vitamin
D, while 29% were insufficient in vitamin D, resulting in a
total of 78% with deficiency or insufficiency in vitamin D.
Also, we found that the vitamin D deficiency group in-
cluded elderly patients.
In accordance with our findings, 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 deficiency and
6.5% had vitamin D insufficiency. 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 insufficient evidence to link vitamin D levels with
COVID-19 severity and mortality.
The current study evaluated the effect of vitamin D
deficiency on the inflammatory 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 inflammatory markers in the vitamin
Ddeficiency group when compared to the other two
groups.
Our findings agree with a previous study by Yilmaz and
S
¸en,
29
which found that vitamin D may reduce the incidence
of inflammatory 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-inflammatory cytokines. Vitamin
D has been reported as a modulator of the immune re-
sponse of macrophages, preventing them from releasing
several inflammatory 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 coefficient.
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 Inflammation

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 inflammatory markers used in clinical
practice to assess the severity of COVID-19. Significant
negative correlations were reported between lower vitamin
D levels and higher inflammatory markers CRP, ferritin,
and D-dimer. In accordance with our findings, 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 inflam-
mation and the cytokine storm. Moreover, Ricci et al.
26
found a significant relation between high levels of D-dimer
and low levels of vitamin D.
The relationship between vitamin D and inflammatory
diseases has triggered a lot of debate because the mech-
anism of the link between low vitamin D concentrations
and increased inflammatory 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 deficiency and lung inflammation
was contradictory and the relationship between vitamin D
deficiency and mortality was ambiguous. Vitamin D defi-
ciency is prevalent in hospitalized patients with severe
illnesses, especially in those who are critically ill.
33–35
There are several conflicting 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
D–binding 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 inflammatory dis-
eases. Amrein et al.
38
revealed that vitamin D levels as-
sessed at the beginning of an acute inflammatory 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 inflammatory 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 first line of host defense, preventing them from the
production of excessive inflammatory cytokine and che-
mokine.
40
The value of vitamin D sufficiency 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 deficiency 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–
deficient group in comparison to other groups. Patients
who were deficient in vitamin D had a higher frequency of
fever and fatigue in comparison to the other groups, and the
difference was statistically significant. 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 defi-
ciency and the severity of the disease. Moreover, Ilie et al.
22
found a significant 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 deficiency 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
deficiency 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 deficiency was as-
sociated with increased levels of inflammatory 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 Inflammation

Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The author(s) disclosed receipt of the following financial 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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