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Mashhad University of
Medical Sciences
(MUMS) Reviews in Clinical Medicine
Rev Clin Med 2023; Vol 10 (No 3)
Published by: Mashhad University of Medical Sciences (http://rcm.mums.ac.ir)
6
Clinical Research
Development Center
Ghaem Hospital
*Corresponding author: Majid Ghayour-Mobarhan,
International UNESCO Center for Health Related Basic Sciences and
Human Nutrition, Department of Nutrition, Faculty of Medicine, Mashhad
University of Medical Sciences, Mashhad, Iran.
E-mail: ghayourm@mums.ac.ir
Tel : +985138002288
This is an Open Access article distributed under the terms of the
Creative Commons Attribution License (http://creativecommons.
org/licenses/by/3.0), which permits unrestricted use, distribution,
and reproduction in any medium, provided the original work is
properly cited.
Psychological Function and Serum Vitamin D Concentration in
COVID19- Patients: A cross-sectional study
Zahra Khorasanchi (PhD)1,2#, Mohammad Vahedi Fard (BSc)3, Kimia Mohammadhasani (BSc)3#,
Yasamin Sharifan (MD)2, Zahra Dehnavi (PhD)1,2,Ramtin Naderian (MD)2,
Ali Jafarzadeh Esfehani (MD-PhD)4, Payam Sharifan (MD-PhD)1, Reza Zare-Feyzabadi (PhD)5,
Gordon Ferns (PhD)6, Majid Ghayour Mobarhan (MD-PhD)5*
1Department of Nutrition, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
2Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
3Department of Nutrition, Food Sciences and Clinical Biochemistry, School of Medicine, Social Determinants of Health Research Center,
Gonabad University of Medical Science, Gonabad, Iran .
4Metabolic Syndrome Research Center. Mashhad University of Medical Sciences, Mashhad, Iran.
5International UNESCO Center for Health Related Basic Sciences and Human Nutrition, Department of Nutrition, Faculty of Medicine,
Mashhad University of Medical Sciences, Mashhad, Iran.
6Brighton and Sussex Medical School, Division of Medical Education, Brighton, United Kingdom.
#Equally contributed as first authors.
Introduction
A cluster of previously unknown pneumonia was
reported, in Wuhan, China in December 2019 (1).
Since, COVID-19 has spread globally, infecting more
deaths as of December 2021 (2).
To hinder the fast propagation of COVID-19,
imposed worldwide, reducing outdoor activities
and interpersonal interactions (3). The extreme
changes caused by the pandemic have contributed
ARTICLE INFO ABSTRACT
Article type
Original article
Article history
Received: 10 Jul 2023
Revised: 30 Jul 2023
Accepted: 15 Aug 2023
Keywords
Vitamin D
COVID-19
Psychological function
Depression
Introduction: The pandemic of COVID-19 created a psychological response. So, the
psychological function of COVID-19 patients is an important subject that forces us to
follow up with them.
Aim: Assess the correlation between vitamin D serum concentrations and
psychological functions such as insomnia, stress, and depression through the
COVID-19 pandemic
Methods: In this cross-sectional study, blood samples from 120 COVID-19 patients
(61 males and 59 females) who had more than 30 years, were taken. Also, 25(OH)D
Serum level of COVID-19 patients was analyzed. The Insomnia Severity Index (ISI),
Depression anxiety stress scales (DASS), and the Short Form Health Survey (SF-36)
were used to analyze insomnia, anxiety, stress, quality of life, and depression.
Results: The relationship between temperature (p=0.039), PCO2 (p=0.022), and
between stress (p=-0.023, OR=0.389, 95% CI for OR=0.047, 0.843), depression
(p=0.012, OR=0.659, 95% CI for OR=0.476, 0.913), and the concentration of serum
vitamin D.
Conclusion:This study recommends that vitamin D supplementation improve
psychological state in COVID-19 patients.
Please cite this paper as:
Khorasanchi Z, Vahedi Fard M,Mohammadhasani K, Sharifan Y, Dehnavi Z, Naderian R, Jafarzadeh Esfehani A, Sharifan P, Zare-Feyzabadi R,
Ferns G, Ghayour Mobarhan M. Psychological Function and Serum Vitamin D Concentration in COVID-19 Patients: A cross-sectional study.
Rev Clin Med. 2023;10 (3): 6-12.
Rev Clin Med 2023; Vol 10 (No 3)
Published by: Mashhad University of Medical Sciences (http://rcm.mums.ac.ir)
7
Khorasanchi Z et al
contributed to the emergence of a psychological
health crisis in many countries, as various studies
have demonstrated (4,5). Studies have shown an
association between economic stagnation and
massive lockdowns due to the pandemic and an
escalation in suicide rates, and the prevalence of
depressive traits has increased more than three
times since the pandemic’s beginning (6,7,8).
UNICEF has reported, social isolation as a
COVID-19 consequence impairs the psychological
health of Australian teenagers in terms of increasing
their levels of anxiety (9). Social isolation has also
contributed to loneliness, boredom, stress, and fear
(9, 10). People with psychological health situations
before, are even at higher risk for deterioration or
recurrence of their symptoms (11,12).
However, the degree of susceptibility to the
psychological distress imposed by the pandemic
depends on social support, exposure to mass media,
duration of isolation, infection conditions, and
lifestyle habits, including nutrition (13). Previously, a
relationship between neuropsychological situations
like depression and bipolar disorder and vitamin D
Vitamin D (25(OH)D) is a neuroactive substance
development in the central nervous system (16,
17). Vitamin D regulates mood via increasing brain
serotonin availability by increasing the expression of
tryptophan hydroxylase two enzymes. This enzyme
(18). Therefore, low levels of vitamin D causes
psychological disorder. Also, vitamin D inadequacy
interleukin-6 by increasing nuclear-factor kappa B
expression (19).
of mental disorders like depression and anxiety
(20). Furthermore, decreased vitamin D level is
connected with altered responses to stressors and
traumatic events (21,22). A meta-analysis revealed
vitamin D and the risk of depression. It recommends
that the supplementation of vitamin D could be
helpful in depressive patients with hypovitaminosis
(23). Additionally, vitamin D supplementation has
shown a considerable enhancement in symptoms
of individuals diagnosed with depression in
comparison to placebo, which could highlight a
causal association between reduced vitamin D
concentration and depressive traits (24,25).
However, vitamin D function in depression is still
debated and requires more study (23,26,27). As
the population, with more than a billion individuals
affected by it globally, the importance of investigating
its different effects cannot be stressed more at the
time of the pandemic (28).
Therefore, we aimed to estimate the correlation
between vitamin D serum concentrations and
mental function in the COVID-19 pandemic.
Materials and Methods
Study design
In 2021, our cross-sectional study was administered
in Imam Reza Hospital in Mashhad, on 120 patients
with COVID-19 who were aged >30 years. Without
anti-depressant drug treatment, hepatic or renal failure,
cancer, metabolic bone disease, and autoimmune
diseases throughout the previous six months were
the exclusion criteria. Informed written consent was
the Ethics Committee of MUMS (Mashhad University of
Medical Sciences), Mashhad, Iran.
All the participants in the main study who met the
inclusion criteria were included in this study based on
global sampling (29).
General and clinical characteristics
characteristics such as smoking status, age, and the
data of comorbidity from each subject by professional
questioner.
Blood Collection and Biochemical Measurements
Blood samples were collected from all subjects
following a 12-hour fasting period in plain Vacutainer
tubes. All blood samples were centrifuged at 5000
serum levels were evaluated by commercial ELISA kits
(Pishgaman Sanjesh- Iran) using an Awareness/Stat
Fax 2100 analyzer.
Depression anxiety stress scales (DASS)
To evaluate mood status, we used DASS (30). DASS
is a questionnaire that includes three subscales and
consists of 7 questions, generally consists 21 items.
Every question is on a four-point (0-3) Likert scale to
recognize the intensity of affective disorders like stress,
anxiety, and depression.
Every item score should be doubled, as DASS 21 is
a summarized version of DASS 42. In DASS, a higher
score reveals an increased in negative emotion, and a
lower score shows a decreased in negative mood status.
The validity and reliability of DASS have been reported
in the Iranian population before (31). The scores of
stress, anxiety, and depression were separated into
degree of affective disorders. The scores received from
Rev Clin Med 2023; Vol 10 (No 3)
Published by: Mashhad University of Medical Sciences (http://rcm.mums.ac.ir)
8
Khorasanchi Z et al.
Insomnia Severity Index (ISI)
The ISI is a self-report tool for determining insomnia
that has seven items. The dimensions evaluated are
the distress caused by sleep problems, noticeability of
sleep disorders by others, early morning waking up
problems, interference of sleep problems with daytime
functioning, sleep dissatisfaction, severity of sleep onset,
and sleep preservation (32).
According to the severity, every item scored on a
0–4 scale. The overall scale ranges from 0 to 28 and is
insomnia (8–14), mild insomnia (15–21), and severe
insomnia (22–28). The reliability and validity of the
Persian version of this questionnaire have been proved
in the Iranian population (Cronbach’s a>0.8 and intra-
Quality of Life Questionnaire
We used SF-36 validated questionnaire to assess the
general quality of life. SF-36 is categorized into eight
subscales, including Mental Health, Role Emotional,
Vitality, General Health, Physical Functioning, Role
Physical, and Bodily Pain Social Functioning. This
questionnaire’s scoring ranges from 0 to 100. The SF-
36 Persian version was evaluated in a prior study and
showed construct validity and good reliability (34).
Statistical analysis
We used the statistical package for social sciences
(SPSS) version 16 for analyzing data. The normality
distribution of continuous variables was estimated
using the Kolmogorov-Smirnoff and Shapiro-Wilk tests.
Normally and non-normally distributed variables were
presented using mean and standard deviation (SD);
were presented using mean and standard deviation
(SD); and median and interquartile range (IQR),
respectively. The data was double-checked to correct
errors regarding outliers and missing variables.
For the remaining missing variables, multiple
imputation was performed based on gender, age, and
other related variables to the missing variables using
the SPSS software. We compared usually distributed
and non-normally distributed variables between
groups using the independent t-test and Mann-Whitney
test, respectively. The chi-square test was performed
to compare the distribution pattern of categorical
variables between groups.
Also, we used Binary logistic regression to evaluate
the relationship between achieving serum vitamin D
>30 ng/mL after the intervention as the dependent
variable, and the scores of DASS-21 subscales, total
SF-36, ISI, and sleep quality scores, as independent
as p<0.05.
Results
One hundred twenty patients (59, 49.1% females and
61, 50.9% males) cooperated in the current study. The
mean age of the patients was 60.38±13.61 years old. We
separated subjects into two groups;1) the level of serum
vitamin D 30 ng/mL or above, and 2) serum vitamin D
below 30 ng/mL. Comparison of the demographic and
medical history variables between subjects with levels
of serum vitamin D above 30 ng/mL and below 30 ng/
mL are presented in Table 1.
Variable Vitamin D < 30 ng/mL
n=68
Vitamin D > 30 ng/mL
n=52 p-value
Gender Male 35 (57.9%) 26 (42.1%) 0.870
Female 33 (56.4%) 26 (43.6%)
Residential status Male 64 (57.1%) 48 (42.9%) 0.395
Female 5 (62.5%) 3 (37.5%)
Hypertension 26 (55.3) 21 (44.7%) 0.721
Diabetes 24 (52.2%) 22 (47.8%) 0.359
CVD 14 (56.0%) 11 (44.0%) 0.884
Smoking 57 (60.0%) 38 (40.0%) 0.146
Table 1. Comparison of demographic and medical history variables between patients with serum vitamin D levels above 30 ng/mL
and below 30 ng/mL
and In Our study the level of serum vitamin
D was 30 ng/mL or above in 52 (42.9%) of the
in demographic and medical history variables
between patients with levels of serum vitamin D
below above 30 ng/mL (p>0.05).
A comparison of the clinical variables, DASS-21
subscale, SF-36, and sleep quality scores with the
levels of serum vitamin D below and above 30 ng/
mL is presented in Table 2.
temperature (p=0.039) and PCO2 (p=0.022) of
The relationship between DASS-21 subscales, SF-36,
and ISI scores and improved serum vitamin D in the
study patients are presented in Table 3.
(p=-0.023, OR=0.389, 95% CI for OR=0.047, 0.843)
and depression (p=0.012, OR=0.659, 95% CI for
OR=0.476, 0.913) and Vitamin D levels.
Rev Clin Med 2023; Vol 10 (No 3)
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Khorasanchi Z et al
Variable Vitamin D < 30 ng/mL
n=64
Vitamin D > 30 ng/mL
n=48 p-value
Pulse rate (/min) 87.00 (14.50) 90.85±10.46 0.201†
Respiratory rate (/min) 21.96±3.65 27.00±5.63 0.326‡
Temperature 37.00 (0.63) 37.15±0.31 0.039*†
SBP (mmHg) 133.27±20.57 131.77±23.61 0.694‡
DBP (mmHg) 80.15±16.26 79.62±13.85 0.854‡
SPO2 (%) 83.50 (12.75) 89.00 (12.00) 0.320†
O2 saturation (%) 73.15 (6.45) 65.40 (37.25) 0.311†
PaO2 (mmHg) 41.65±13.54 33.10 (24.35) 0.418†
PCO2 (mmHg) 40.72±11.15 48.18±17.67 0.022*†
Depression 9.00 (9.25) 7.00 (3.50) 0.090†
Anxiety 13.00 (9.50) 11.92±3.90 0.491†
Stress 10.50 (9.50) 10.00 (6.50) 0.907†
Quality of life 53.77±18.04 59.32±20.25 0.864‡
Insomnia Severity Index 2.00 (10.00) 1.00 (5.50) 0.665†
Table 2. Comparison of clinical variables and scores in DASS21- subscales, SF36-, and insomnia between
patients with serum vitamin D levels above 30 ng/mL and below 30 ng/mL
SBP: Systolic Blood Pressure, DBP: Diastolic Blood Pressure, SPO2: Blood Oxygen Saturation, PaO2: Arterial
Oxygen Pressure, PCO2: Arterial carbon Dioxide Pressure, min: Minute, mmHg: Millimeters Mercury, mEq:
Milli Equivalent, L: Liter,
Table 3. Relationship between depression, stress anxiety, quality of life and insomnia scores and improved
Variable B Wald p OR 95% CI for OR
Lower Upper
Depression -0.416 6.282 0.012* 0.659 0.476 0.913
Anxiety -0.105 0.689 0.407 0.901 0.704 1.153
Stress -0.329 5.191 0.023* 0.389 0.047 0.843
Insomnia -0.085 1.997 0.158 0.918 0.816 1.033
Quality of Life -0.009 0.246 0.620 0.991 0.955 1.028
Binary logistic regression was done.
These results revealed that with one point increase in
depression scores, the risk of achieving vitamin D levels
above 30 mg/mL decreases by 34.1%. Furthermore,
with one point increase in stress core, the risk of
achieving vitamin D levels above 30 ng/mL decreases
by 38.9%. Although we obtained all these results, more
to determine all the mechanisms that vitamin D affects
psychological function.
Discussion
In this cross-sectional study, the correlation between
vitamin D concentration and psychophysiological
factors among 120 COVID-19 patients was assessed.
levels of vitamin D and reduced depression and stress
in patients. The correlation between vitamin D and
mental disorders has been investigated in various
studies (35,36,37).
the reduced severity of mental effects caused by
COVID-19 and 25(OH) D concentrations (at least 30
ng/mL). In line with our study, some experimental
between increased major depression and vitamin
OH-D3 levels increase the severity of depression
(39). Murphy et al. found that a reduced level of
serum 25(OH) D is associated with depression (40).
Also, a meta-analysis of cohort and cross-sectional
studies suggested that depressive disorders are
related to reduced vitamin D concentrations (41).
It can be due to the extensive impact of
Vitamin D on modulating mental function,
including neurotransmitter release (42,43,44),
neuroprotection (45, 46), maintaining cognitive
ability (47, 48), and protection against adverse
outcomes of chronic stress (49,50).
Rev Clin Med 2023; Vol 10 (No 3)
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Khorasanchi Z et al.
neurotransmitters such as glutamate, serotonin,
and dopamine (51).
and oxidative stress. Selective Serotonin
Reuptake Inhibitors (SSRI) are used to reduce the
the brain. (52) Also, oxidative stress is associated
with depression by damaging DNA (53). The
supplementation of vitamin D increases the gene
expression that correlates with antioxidation
glutathione reductase) (54).
Therefore, vitamin D decreases oxidative
stress and improves depression. One of the
most COVID-19 outcomes is stress which affects
psychological stability (55). Our study revealed
that the levels of vitamin D are associated with
pressure in COVID-19 patients. Tehrani et al.
indicated that adults had higher priority and had
lower levels of vitamin D (56).
Another study revealed that higher vitamin
D levels reduce stress (57). Also, Trovato et al.
found that increased consumption of vitamin
D or sunlight exposure is related to lower
perceived stress among participants (58). In
between stress in another study and vitamin D
levels (59). Reducing stress may be related to the
improvement of depression (57).
So, it helps COVID-19 patient’s mental health
and decreases stress.
We have some limitations in our study. At
patients, which can limit the generalization of the
results to other populations. We included patients
who had recorded 25(OH) D concentrations. Some
confounding factors, like social, economic status
and smoking, did not register for all participants
and might have a reasonable effect on the severity
of COVID-19. Additionally, the RT-PCR test has not
been performed on all participants with COVID-19
clinical signs. Second, our study is cross-sectional.
depression or stress among COVID-19 patients.
In conclusion, this study revealed that vitamin
D concentrations are related to depression and
stress. A higher concentration of serum vitamin D
may decrease depression and stress risk among
COVID-19 patients. Additional longitudinal large-
the pathophysiology of COVID-19 symptoms.
some of the associated symptoms of COVID-19
may be prevented or improved through nutritional
interventions both at the community and
hospital levels. Furthermore, physicians might
better anticipate of the prognosis of symptoms
in COVID-19 patients who present degrees of
depression and stress.
Ethical statements
Acknowledgment
We sincerely thank all patients participating in
this study.
Funding
This study is supported by Mashhad University
of Medical Sciences (grant nu: 981873).
Availability of data and materials
The datasets collected and/or analyzed during
the present study are not publicly accessible due
to ethical concerns, but the corresponding author
may provide datasets upon reasonable request.
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