COVID-19 AND VITAMIN D – A SYSTEMATIC REVIEW
Taja JORDAN1,a,*, Darko SIUKA2,a, Nada KOZJEK ROTOVNIK3,4, Marija PFEIFER3
1University Medical Centre Ljubljana, Department for Radiology, Zaloška c. 7, 1000 Ljubljana, Slovenia
2University Medical Centre Ljubljana, Department for Gastroenterology, Zaloška c. 7, 1000 Ljubljana, Slovenia
3University of Ljubljana, Faculty of Medicine, Vrazov trg 2, 1000 Ljubljana, Slovenia
4Institute of Oncology Ljubljana, Department for Clinical Nutrition, Zaloška c. 2, 1000 Ljubljana
Received: Aug 20, 2021
Accepted: Feb 22, 2022
Review
*Corresponding author: Tel. + 386 40 257 987; E-mail: taja.jordan@gmail.com
aThese authors contributed equally to this work.
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COVID-19 IN VITAMIN D – SISTEMATIČNI PREGLEDNI ČLANEK
© National Institute of Public Health, Slovenia. 
Jordan T, Siuka D, Kozjek Rotovnik M, Pfeifer M. COVID-19 and vitamin D – a systematic review. Zdr Varst. 2022;61(2):124-132. doi: 10.2478/sjph-2022-0017.
ABSTRACT
Keywords: 
COVID-19, vitamin D, 
systematic reviews
IZVLEČEK
Ključne besede: 
COVID-19, vitamin D, 
sistematični pregledi
Introduction: The COVID-19 pandemic has strongly affected global healthcare systems. Prior epidemiological 
studies on different infectious diseases have shown a strong correlation between serum vitamin D levels and 
the incidence of certain infectious diseases. Vitamin D has an important immunomodulatory effect on innate 
immunity and exhibits several other mechanisms in the pathogenesis of the cytokine storm, which is one of the 
main contributing factors to fatality in COVID-19 patients.
Methods: A keyword search was conducted in the PubMed and Google Scholar research databases. The abstracts 
and/or full texts of selected papers were further evaluated. Articles that fulfilled the inclusion criteria were 
included in the systematic review.
Results: The 28 studies summarized in this review provide observational findings that vitamin D levels are 
related to the incidence, severity, and mortality rate of COVID-19 infection. The literature does not suggest 
that COVID-19 could be eliminated with supplementation of vitamin D, but there are implications that vitamin D 
deficiency might increase the risk for COVID-19 infection and severity of the disease progression.
Discussion: Current literature and several guidelines support the supplementation of vitamin D as a reasonable 
strategy for correcting and preventing vitamin D deficiency. The recommended dose for maintaining normal 
25(OH)D levels by consensus is 1000 to 2000 IU vitamin D daily for at-risk teens and adults. 
Conclusion: Vitamin D supplementation might play an important role in protecting from acute respiratory 
infections like the SARS CoV2, and in high-risk individuals with COVID 19 from progressing to critical clinical 
condition and reducing mortality.
Uvod: Pandemija COVID-19 je močno zamajala zdravstvene sisteme po svetu. Predhodne epidemiološke študije 
o različnih nalezljivih boleznih so pokazale močno povezavo med ravnjo vitamina D v serumu in incidenco 
nekaterih nalezljivih bolezni. Znano je, da ima vitamin D pomemben imunomodulatorni učinek, ki okrepi 
prirojeno imunost. Poleg tega ima vitamin D tudi številne druge mehanizme, vključno z ublažitvijo citokinskega 
viharja, ki je eden glavnih dejavnikov obolevnosti in smrtnosti pri bolnikih s COVID-19.
Metode: Iskanje po ključnih besedah je bilo izvedeno v raziskovalnih podatkovnih bazah PubMed in Google 
Scholar. Povzetki in/ali celotna besedila izbranih, potencialno pomembnih prispevkov so bili nadalje ocenjeni. 
Članki, ki so ustrezali merilom, so bili vključeni v sistematični pregled.
Rezultati: V preglednem članku je povzetih 28 študij, ki obsegajo ugotovitve, da so ravni vitamina D tako ali 
drugače povezane z incidenco, resnostjo bolezni in stopnjo umrljivosti zaradi okužbe s COVID-19. Literatura 
ne kaže, da bi lahko COVID-19 odpravili z dodatkom vitamina D, vendar obstajajo podatki, da pomanjkanje 
vitamina D lahko poveča tveganje za okužbo s COVID-19 in je povezano s hujšo stopnjo obolevnosti in smrtnosti.
Diskusija: Trenutna literatura in več smernic podpirajo dodajanje vitamina D kot razumno strategijo za odpravo 
in preprečevanje pomanjkanja vitamina D. Priporočeni odmerek za vzdrževanje normalne ravni 25(OH)D s 
konsenzom je 1000 do 2000 IE vitamina D na dan za ogrožene najstnike in odrasle.
Zaključek: Dodatek vitamina D pri posameznikih s pomanjkanjem vitamina D ima lahko pomembno vlogo pri 
zaščiti posameznikov pred akutnimi okužbami dihal ter pri tistih z visokim tveganjem za hud potek COVID-19 
in smrt zaradi te bolezni.
1 INTRODUCTION
The COVID-19 pandemic has strongly affected global 
healthcare systems. In the early spring of 2020, a severe 
acute respiratory syndrome coronavirus 2 (SARS CoV2) 
crisis began in European countries, with many critical 
cases and deaths, particularly in high-risk groups. 
Several retrospective analyses were performed, observing 
the effects on different disease courses, and other reasons 
for the clinical outcome differences were questioned. 
According to the reported data, there are seasonal 
fluctuations of COVID-19 disease severity (1).
It has been known for decades that seasonal changes cause 
significant immunity variation, including fluctuations in 
lymphocyte response and circulating levels of lymphocytes 
and neutrophils (2, 3). Epidemiological studies have shown 
also a strong reverse correlation between serum vitamin D 
(25-hydroxyvitamin D, 25(OH)D) levels, which are normally 
higher during the summer season, and the incidence of 
certain infectious diseases (2, 3). Vitamin D induces 
cathelicidin and beta defensin transcription and synthesis 
in macrophages and a favourable anti-inflammatory Th1 
to Th2 phenotype ratio. Additionally, vitamin D exhibits 
a mitigating effect on the pathogenesis of the cytokine 
storm, which is one of the main contributing factors to 
fatality in COVID-19 patients (4). Vitamin D showed also 
potent activity against SARS CoV 2 in vitro (5). 
Factors that have been shown to contribute to vitamin D 
deficiency include older age, smoking, higher body mass 
index (BMI) and obesity, lack of proper sun (UVB) exposure, 
dark skin and the presence of chronic illnesses, such as 
diabetes, malignant disease, high blood pressure, various 
gastrointestinal disorders and many others. Most people 
with these risk factors have been shown to be at increased 
risk regarding both severity of the disease and mortality 
from COVID-19 (6). Ethnic differences in the prevalence 
of common genetic polymorphisms of vitamin D receptor 
(VDR) and a series of cytochrome P450-containing sterol 
hydroxylases provide an additional explanation for low 
vitamin D levels. The exact role of genetic background in 
the responsiveness to vitamin D supplementation is yet to 
be determined (7).
In Slovenia, epidemiological data about vitamin D status 
in the population were investigated by a nationwide 
Nutrihealth study in 2017/18. A particularly concerning 
situation was observed during extended wintertime 
(November–April); severe vitamin D deficiency (defined 
as 25(OH)D levels below 30 nmol/L) was found in 40.8% 
of adults (age 18 – 64 years) and 34.6% of elderly people 
(age 65 to 74 years), while levels below 50 nmol/L 
(vitamin D deficiency) were observed in 81.6% and 
78.8%, respectively. The results of the study showed high 
seasonal variations in serum 25(OH)D levels in both the 
adult and elderly population. The prevalence of vitamin 
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D deficiency in Slovenia is among the highest in Europe 
and poses a serious public health risk that needs to be 
addressed with appropriate recommendations and policy 
interventions (8).
In 2021 a Slovenian systematic review of vitamin D status 
and dietary intake in various Slovenian populations was 
published. A meta-analysis of 43 studies that addressed 
serum 25(OH)D status and 16 that addressed vitamin D 
intake was conducted. The results showed that various 
population groups across Slovenia are at high risk of 
vitamin D insufficiency and deficiency, particularly during 
wintertime. All included studies reported daily intakes 
below the recommended level (9).
In Slovenia, because of the COVID-19 pandemic, medical 
doctors and the general population were urgently advised 
by leading experts to supplement vitamin D in fragile, 
vitamin D deficient high-risk individuals and COVID-19 
patients (10, 11). At the beginning of the COVID-19 
pandemic there were no data on the effects of vitamin 
D in SARS-CoV-2 infection; then again, there were 
reliable data on the beneficial effects of cholecalciferol 
in attenuating viral respiratory infections in people with 
low levels of vitamin D (12). The European Centre for 
Disease Prevention and Control encouraged health care 
professionals to take actions that are logical, based on 
previously known findings in related fields (13). However, 
in more than a year of the COVID-19 pandemic new data has 
become available to support the important role of vitamin 
D in SARS-CoV-2 infection, and some recommendations of 
vitamin D supplementation are already available (8-10). 
Several studies have investigated the correlation between 
serum 25(OH)D levels and the incidence, severity and 
mortality of COVID-19 patients. The objective of this 
systematic review was to review the studies that explored 
the relationship between vitamin D and the course of 
COVID-19. The aim of our study was to explore whether 
optimal vitamin D status mitigates COVID-19 and if vitamin 
D supplementation is beneficial in the phase of COVID-19 
pneumonia. 
2 MATERIALS AND METHODS
2.1 Literature search strategy
The systematic review was prepared following the PRISMA 
recommendations (17).
2.2 Search strategy
We used the PubMed and Google Scholar research 
databases to search for published research (18, 19). 
The search command consisted of the following MeSH 
Terms: (Vitamin D AND COVID-19) and was narrowed to 
search in titles and abstracts. Abstracts were then examined 
by two independent observers. Studies available in full 
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text that included key terms in the title or abstract were 
considered. The abstracts and/or full texts of selected, 
potentially relevant papers were further evaluated.
Two independent reviewers (D.S., T.J.) completed a study 
identification and selection search in MEDLINE and Google 
Scholar, and disagreements were discussed with another 
reviewer (N.R.K.). 
2.3 Methods of inclusion and exclusion criteria 
The selection was limited to surveys published in English 
in 2020. The last inquiry was made on 30th November 
2020. By reviewing the titles and abstracts, articles 
that were assessing the impact of vitamin D on COVID-19 
infection in participating subjects or in populations were 
chosen. We searched for outcomes of COVID-19 (severity 
or/and mortality or/and incidence). For the purpose of 
our research the association of vitamin D and COVID-19 
was divided into two groups: positive or negative (YES or 
NO), positive association meaning there was a statistically 
significant association between higher vitamin D levels 
and better outcome of COVID-19. Only studies with 
accessible full text and quantitatively reported outcomes 
were included. 
The exclusion criteria for articles were: no accessible 
full text, publications with only abstracts, posters, 
editorials and comments available. Articles for paediatric 
populations and case studies were also excluded.  Studies 
that did not report specific outcomes quantitatively were 
also excluded.
3 RESULTS
3.1 Search results and study selection
The search of PubMed returned 321 articles and Google 
Scholar returned 574 articles. By following the inclusion 
and exclusion criteria explained in the method section, 
and after removing duplicates, the number of articles 
fell to 361. After reading the abstracts, we found 58 full 
text articles eligible for full reading. After reading the 
full texts, we excluded 30 articles not assessing either 
the severity, mortality or the incidence of COVID-19. We 
also excluded editorials, systematic reviews, case studies, 
studies of paediatric population and in vitro studies. A 
study assessing the impact of vitamin D together with other 
micronutrients on COVID-19 severity was also excluded. 
A total of 28 articles were relevant for the purpose of 
content analysis (Figure 1).
3.2 General description of selected documents
The final number of studies included in the research was 
28. All studies were published in 2020. We collected data 
on the country where the research was conducted, the 
number of participants, the number of centres included in 
Figure 1. Flowchart of the course of selection of documents in 
the systematic review of the literature on vitamin D 
and COVID, following PRISMA.
the study and the effect of vitamin D on COVID-19. Among 
the included studies were 22 individual-level studies and 
6 population-evel studies. There were 24 observational 
studies and 4 experimental studies.  A positive association 
between vitamin D and COVID-19 was described in 26 
studies and in 2 studies there was no association. The 
results are shown in Table 1.
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Entrenas Castillo 
M et al (20)
De Smet D  
et al (24)
Jain A et al (25)
Merzon E et al (26)
Israel A et al (27)
Meltzer DO 
et al (28)
Kaufman HW 
et al (29)
Hastie CE et al (30)
Daneshkhah 
A et al (31)
Murai IH et al (21)
Rastogi A et al (22)
Annweiler G 
et al (23)
AUTHORS
EXPERIMENTAL STUDIES
OBSERVATIONAL STUDIES
UTCOME
(S-SEVERITY/M-
MORTALITY/
I-INCIDENCE)
Association
(YES/NO)
COUNTRY DESIGN SAMPLE 
SIZE
CENTRE EFFECT OF VITAMIN D ON COVID-19
S,M
S,M
/
S,I
I
I
I
I
I
S,M
/
S,M
YES
YES
YES
YES
YES
YES
YES
NO
NO
NO
YES
YES
Spain
Belgium
India
Israel
Israel
USA
USA
UK
USA
Brazil
India
France
RCT
ROCS
ROCS
ROCS
ROCS
ROCS
ROCS
ROCS
ROCS
DB RCT
RCT
QES
76
186
154
14000
576455
489
190000
502624
4526
240
40
77
1
1
1
/
/
/
50
/
6
2
1
1
Positive association. In the treatment 
group, 2% required admission to 
the ICU, in the control group 50%
Positive association. Vitamin D 
deficiency is correlated with the 
risk for hospitalization for COVID-19 
pneumonia and predisposes to more 
advanced radiological disease stages
Positive association. Vitamin 
D deficiency in COVID-19 
asymptomatic group 32.96% and 
96.82% in symptomatic group
Positive association. The results 
demonstrated that low vitamin 
D levels are an independent risk 
factor for COVID-19 infection and 
hospitalization due to COVID-19 
Positive association. Highly 
significant correlation between 
prevalence of vitamin D deficiency 
and COVID-19 incidence
Positive association. The relative 
risk of testing positive for COVID-19 
was 1.77 times greater for patients 
with deficient vitamin D status 
compared with patients with sufficient 
vitamin D status before disease
Positive association. The SARS-
CoV-2 positivity rate was higher in 
patients with 25(OH)D deficiency 
No association. Pre-infection 
blood samples did not support the 
vitamin D and the SARS-CoV-2 link
Positive association. Vitamin D status 
of a country’s elderly population was 
associated with the number of severe 
cases of Covid-19 in that country
No association. Increased 25(OH)
D levels in severe COVID patients, 
did not reduce hospital length 
of stay or any other relevant 
outcomes compared to placebo 
Positive association. With vitamin D 
supplementation more COVID patients 
turned COVID-19 PCR test negative 
with significant decrease in fibrinogen
Positive association. Regular 
bolus vitamin D supplementation 
was associated with less severe 
COVID-19 and better survival in frail 
elderly nursing home residents
Table 1. Analyses reviewing the effect of Vitamin D on COVID-19 infection, individual-level studies.
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Hernandez  
et al (32)
Fasano et al (33)
Maghbooli Z 
et al (34)
D’Avolio A  
et al (35)
Carpagnano GE 
et al (36)
Baktash V  
et al (37)
Mardani Ret al (38)
Radujkovic A 
et al (39)
Karahan S  
et al (40)
Faniyi AA (41)
AUTHORS UTCOME
(S-SEVERITY/M-
MORTALITY/
I-INCIDENCE)
Association
(YES/NO)
COUNTRY DESIGN SAMPLE 
SIZE
CENTRE EFFECT OF VITAMIN D ON COVID-19
S
S
S
I
S,M
S,M
I
S,M
S,M
I
YES
YES
YES
YES
YES
YES
YES
YES
YES
YES
Spain
Italy
Iran
Swizerland
Italy
UK
Iran
Germany
Turkey
UK
ROCS
ROCS
ROCS
ROCS
ROCS
ROCS
ROCS
ROCS
ROCS
ROCS
413
2693
235
107
42
105
123
185
149
392
1
1
1
1
1
1
1
1
1
1
Positive association. 25(OH)D levels 
are lower in hospitalized COVID-19 
patients than in population
Positive association. Vitamin D 
supplementation was protective 
for developing COVID-19 in 
patient with Parkinson disease
Positive association between sufficient 
vitamin D levels and the reduction 
in clinical severity for COVID-19
Positive association. Significantly 
lower 25(OH)D levels were found in 
PCR-positive for SARS-CoV-2 patients 
compared with negative patients
Positive association. Significantly 
higher mortality rate among patients 
with vitamin D deficiency in the ICU
Positive association. Patients 
with vitamin D deficiency and 
COVID-19 may demonstrate 
worse morbidity outcomes
Positive association. Angiotensin-
converting enzyme (ACE) 
concentration showed a higher 
quantity among individuals 
with COVID-19 with insufficient 
vitamin D concentration
Positive association. Vitamin D 
deficiency was associated with 
higher risk of invasive mechanical 
ventilation and death 
Positive association. Mean serum 
25(OH)D was significantly lower in 
patients with severe-critical COVID-19 
compared with moderate COVID-19
Positive association. UK health 
professionals with vitamin D 
deficiency were more likely to be 
seropositive for COVID-19 antibodies
*RCT-Randomized controlled trial, DB RCT-Double blind randomized controlled trial, QES-Quasi-experimental study, ROCS-Retrospective 
observational cohort study, POCS-Prospective observational cohort study, Mendelian randomization. OUTCOME: severity/mortality of 
COVID-19 in relation to 25(OH)D levels – S,M; incidence of COVID-19 infection in relation to 25(OH)D levels – INC, interventional studies 
with vitamin D replacement – INT
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Moozhipurath 
RK et al (42)
Jüni P et al (43)
Ilie et al (44)
Singh et al (45)
Notari A et al (46)
Li M et al (47)
AUTHORS
EKO
UTCOME
(S-SEVERITY/M-
MORTALITY/
I-INCIDENCE)
Association
(YES/NO)
COUNTRY DESIGN SAMPLE 
SIZE
CENTRE EFFECT OF VITAMIN D ON COVID-19
I
I
S,M
I
I
I
YES
NO
YES
YES
YES
YES
Germany
Canada
UK
India
Spain
USA
EKO
EKO
EKO
EKO
EKO
EKO
6524
375 609
/
/
/
/
152
144
20
20
50
154
Positive association. UVB 
radiation (indirect vitamin D) 
was associated with lower death 
rates and case fatality rates 
No associations of epidemic 
growth of COVID-19 with 
latitude and temperature
Positive association. Significant 
correlation between low mean 
vitamin D levels for both 
COVID-19 fatalities and cases 
Positive association. Significant 
inverse correlation between 
vitamin D levels and case rates
Positive association. Lower mean 
annual levels of vitamin D were 
linearly related to increased 
COVID-19 infection risk 
Positive association, vitamin D 
was associated with reduced 
COVID-19 infection risk 
Table 2. Analyses reviewing effect of Vitamin D on COVID-19 infection, population-level studies.
*EKO-Ecological study. S-severity, M-mortality, I-incidence
3.3 Detailed qualitative results
3.3.1 Individual-level studies 
Out of 22 individual-level studies, only 4 were 
experimental studies. The majority (3 out of 4) showed a 
positive correlation between vitamin D supplementation 
and COVID-19 infection and only one, the Brazil study, 
showed no correlation. There were 18 observational 
individual-level studies included, with only one showing 
no association between vitamin D levels and COVID-19 
infection.
3.3.2 Population level studies
There were 6 population-level studies included, all of 
them being ecological studies. Only the Canadian study 
had a negative result and did not find any associations 
between epidemic growth of COVID-19 infection and 
latitude and temperature. The other 5 included ecological 
studies showed a positive correlation, where higher 
vitamin D levels were associated with lower incidence of 
COVID-19 infection.
4 DISCUSSION
The 28 articles summarized here provide correlational 
evidence that vitamin D levels impact the incidence, 
severity and mortality rate of COVID-19 infection. Most 
of the observational studies show an inverse correlation 
between vitamin D levels and the severity and mortality 
of the COVID-19 disease. The same results were found in 
two other systematic reviews (48, 49). The majority of 
included observational studies also showed an inverse 
correlation between vitamin D levels and incidence of 
COVID-19, whereas results from the meta-analysis by 
Pereira et al show that vitamin D deficiency was not 
associated with higher incidence of COVID-19 infection 
(48). The demonstration of a significant correlation 
between vitamin D status and COVID-19 incidence, 
severitiy and even mortality may bring important public 
health implications regarding a major public health issue 
represented by vitamin D deficiency in the modern age. 
Five out of 6 ecological studies showed the correlation 
between vitamin D, COVID-19 mortality rate and latitude. 
These population-level studies also show big potential 
in health promotion regarding vitamin D deficiency 
prevention in different parts of the world. But correlation 
does not prove causality. Vitamin D levels are usually 
higher in healthy individuals in whom vitamin D could be 
an indicator of a healthy lifestyle.  
The literature does not suggest that COVID-19 could be 
substantially reduced with supplementation of vitamin 
D, but there are indications that vitamin D deficiency 
increases the risk for COVID-19 infection and severity of 
the disease progression, as it does for other acute viral 
respiratory infections (12). However, there were some 
studies published that did not confirm this hypothesis. 
As for the Brazilian randomized controlled trial, it is 
important to note that the patients received vitamin D 
supplementation in a single very high dose (200.000 IU or 
5000µg) more than a week after the onset of symptoms. 
Patients who required invasive mechanical ventilation and 
those admitted to the ICU were excluded. Additionaly, 
the proportion of patients with 25(OH)D deficiency was 
considerably lower than in other cohorts. (12, 44). A single 
dose of vitamin D might cause long-term induction of the 
inactivating 24-hydroxylase, and induction of fibroblast 
growth factor 23 (FGF23) that can suppress the 1-alpha-
hydroxylase enzyme required for activation of vitamin 
D. Thus regular daily vitamin D supplementation or daily 
loading doses at the beginning of the disease (as soon as 
possible after confirmation of the infection) might have 
better immunomodulatory effects in COVID-19, rather than 
large bolus dosing at the time of severe disease (51, 52). In 
the Indian randomized study, a high-dose cholecalciferol 
turned a greater proportion of COVID-19 infected patients 
to become negative, supporting the thesis of the important 
impact of vitamin D on the innate immunity allowing 
macrophages to lower the viral burden and mitigate the 
COVID-19 course (22). A single study included an analysis of 
VDR and hydroxylase polymorphisms, which could affect 
results obtained across different populations and ethnic 
groups, as well as determine the effect of vitamin D levels 
in certain individuals. One Mendelian randomization study, 
using summary data from genome-wide association studies 
and 25(OH)D concentration-related single nucleotide 
polymorphisms as instrumental variables of genes 
associated with vitamin D deficiency, showed that there 
might be no linear causal relationship between 25(OH)D 
concentrations, susceptibility to COVID-19 infection and 
severity of disease. This randomization did not consider 
other factors influencing serum vitamin D levels, such 
as ambiental UVB (53). Interestingly, a recent Mendelian 
randomization study analysing the relationship between 
genetically determined 25(OH)D levels and all-cause 
mortality found that there was a negative relation only in a 
vitamin deficient area that was exponential but no relation 
between 25(OH)D levels above 50 nmol/L and mortality 
(48). As poor nutritional status compromises the immune 
response and reduces the treatment response to COVID-19 
infection, not just supplementation with vitamin D but 
proper nutritional therapy in combination with vitamin D 
supplements would probably improve the effectiveness of 
COVID-19 treatments (54). Moreover, intake of vitamin D 
supplements is often limited by relatively poor adherence, 
especially in individuals with low-socioeconomic status 
(lower education, marginal groups), who are at the highest 
risk for vitamin D deficiency. Vitamin D deficiency is a 
known challenging public health issue, especially during 
the winter months with high incidence of viral respiratory 
infections (9). An effective approach to improve vitamin 
D status in the general population could be systematic 
vitamin D food fortification, since it is economical, safe 
and decreases deficiency risk in the entire population, 
including people that would not use supplements (55). 
However, current literature supports the supplementation 
of vitamin D as a reasonable strategy for correcting and 
preventing vitamin D deficiency. There are already some 
national ad hoc recommendations addressing vitamin D 
supplementation in fragile, vitamin D deficient high-risk 
individuals for COVID-19. Slovenian as well as some other 
ad hoc recommendations for replacement of vitamin D in 
periods of respiratory infections and COVID-19 pandemic 
suggested supplementation with cholecalciferol in a daily 
dose of 20 to 50µg (800 – 2000 IU) from October to May as 
a preventive measure in healthy individuals who have the 
possibility of safe sun exposure in the summer months (15). 
In individuals with chronic medical conditions and in those 
with less possibility of safe sun exposure in the summer 
between 10 a.m. and 4 p.m. such as healthcare providers, 
a dose of 20 to 50µg was recommended. The same dose 
was recommended also for individuals who share the 
same household with a COVID-19 infected person and 
with a high risk for COVID-19 infection. For hospitalized 
COVID-19 patients a laboratory analysis of serum 25(OH)
D was recommended following vitamin D supplementation 
according to the serum level (56). For national guidelines 
of vitamin D supplementation in the COVID-19 pandemic 
and in periods of viral respiratory infections, data from 
additional studies is needed especially from larger double 
blind randomized placebo-controlled studies. Given 
the lack of highly effective therapies against COVID-19, 
except perhaps for corticosteroids, it is important to 
remain open-minded to emerging results from rigorously 
conducted studies with vitamin D (47). 
The strength of this systematic review is its compliance 
with international standardized guidelines on reporting of 
systematic reviews and a high heterogeneity of included 
studies resulting from the baseline study design and the 
variability of the baseline characteristics. In this review 
different endpoints such as the incidence of COVID-19, 
the severity of COVID-19, length of hospitalizations, 
the need for an intensive care unit and mortality are 
reported, and our results could have a significant impact 
on clinical practice and public health. In view of the 
fact that COVID-19 is a new disease and there is a low 
number of well-planned intervention studies, this was 
the main limitation that influenced the conclusion of this 
research. An additional limitation of our study is that we 
only searched through two bibliographic databases (we 
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10.2478/sjph-2022-0017 Zdr Varst. 2022;61(2):124-132
searched the two largest ones) and there was a relatively 
large number of excluded articles which did not fulfil our 
carefully chosen criteria for inclusion. 
This systematic review with a large number of articles 
included has considerable public health importance 
because it presents a summation of the latest research 
of the immunomodulative impact of vitamin D on the 
COVID-19 course. This review article presents some 
possibilities and ideas for future research. In future, 
randomized double blinded studies are needed, with 
vitamin D supplementation as a preventive measure prior 
to potential infection. 
5 CONCLUSION
Vitamin D supplementation might play a pivotal role in 
protecting individuals from COVID-19. Optimal levels of 
25(OH)D in the early phase of COVID-19 infection could 
prevent progression to severe or critical clinical condition 
and reduce mortality associated with COVID-19. The role of 
acute supplementation of vitamin D in severely deficient 
patients in the late phases of COVID-19 pneumonia is still 
unclear. Therefore, further randomized double blinded 
clinical trials are needed to provide conclusive evidence.
CONFLICT OF INTEREST
We declare no competing interests.
FUNDING
This work was unfunded.
ETHICAL APPROVAL
The method used in this systematic literature review 
involves no ethical issues and ethical approval was not 
necessary.
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