Objective: To explore the possible relationship between vitamin D and coronavirus disease-2019 in an urban population known to have relatively low vitamin D levels.
Method: The retrospective study was conducted in Bursa, Turkey, and comprised data of 30 family health centers from
March 1 to December 15, 2020, related to diagnosed inpatients of coronovairus disease-2019. The diagnosis was based on
polymerase chain reaction test for severe acute respiratory syndrome coronavirus-2 infection. Vitamin D levels of these
patients were obtained from previous records and compared with those without polymerase chain reaction positivity.
Vitamin D levels of positive patients who survived were compared with those who died of coronavirus disease-2019. Data
was analysed using SPSS 21.
Result: Of the 2,105 patients whose data was retrieved, 212(10%) were positive for coronavirus disease-2019, while
1,893(90%) were negative. Among the positive patients, 89(42%) were men and 123(58%) were women. The overall median
age was 45 years (Q1-Q3(Q1: first quartile, Q3: third quartile): 35-56 years). Vitamin D level was not significantly different
between the positive and negative patients (p>0.05). Among the positive patients, 2(0.9%) patients did not have new
admissions to the designated centers and their data was excluded, 206(97.2%) survived and 4(1.9%) died. There was no
significant difference in vitamin D levels between those who survived and those who died (p>0.05).
Conclusion: There was no significant relationship found between vitamin D levels and coronavirus disease-2019 infection
and related deaths.
Keywords: COVID-19, PCR positivity, SARS-CoV-2 infection, Vitamin D. (JPMA 72: 1779; 2022)
Coronavirus disease-2019 (COVID-19) develops due to infection of severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) which uses angiotensin-converting enzyme2 (ACE2) as a primary receptor for entry into human cells. ACE2 receptors are found in different organs and tissues, particularly the lungs.1,2 Vitamin D is an important hormone that is synthesised in the body. It is essential for immune function and modulates host inflammatory responses to infection.3,4 In some studies, vitamin D has been reported to have a possible positive effect in reducing the risk of respiratory tract infections (RTIs). Vitamin D may decrease the viral replication rate and proinflammatory cytokine concentrations by inducing cathelicidins and defensins. This decrease in levels of proinflammatory cytokines reduces inflammation, lung damage and pneumonia.2-7
In a study investigating vitamin D levels in patients with COVID-19, levels of 25-hydroxy vitamin D (25[OH]D) were significantly lower in patients with SARS-CoV-2 infection than those without, and this difference was more pronounced in individuals aged >70 years. Moreover, advanced age and low 25(OH)D levels increase COVID-19-related mortality rates.8
In another study investigating calcium levels in patients with COVID-19, the levels of ionized calcium were lower in >80% of the hospitalised cases compared to those not hospitalised. Hypocalcaemia was associated with admission to the intensive care unit (ICU) and death. Additionally, it hinted that vitamin D deficiency may be related to the occurrence of hypocalcaemia.9
Vitamin D deficiency is common in countries worldwide.10 Exposure to the sun has decreased because of the need to spend more time at home during the pandemic. This situation may worsen the issue of deficiency of vitamin D in the long term. Therefore, vitamin D supplementation may effectively prevent acute RTIs in patients with vitamin D deficiency and serum 25(OH)D level <20ng/mL.11-13
Although there is no definite and precise data about the effects of vitamin D levels and administration of vitamin D supplements on COVID-19,2 vitamin D may play a protective role in preventing and treating the disease.
As such, the current study was planned to explore the possible relationship between vitamin D and COVID-19 in an urban population known to have relatively low vitamin D levels.
Materials and Methods
The retrospective study was conducted in Bursa, Turkey, and comprised data of 30 family health centers from March 1 to December 15, 2020, related to diagnosed inpatients of COVID-19. After approval from the ethics review committee of Bursa Uludağ University, Bursa, the sample size was determined on the basis of our previous study10 that had examined vitamin D levels in17,812 cases. These examined cases were taken as a population, and the sample was raised by randomly including individuals in the light of the official COVID-19 incidence rate noted by the Ministry of Health with margin of error d=0.009 at alpha=0.05. The COVID-19 diagnosis was based on polymerase chain reaction (PCR) test for SARS-CoV-2 infection. The data was accessed after permission from the Turkish Ministry of Health.
Demographic information, vitamin D levels, and patients' comorbidities were noted. The vitamin D levels of these patients had been measured at the designated family health centers and recorded in their individual their files within the preceding two years. Vitamin D level of the positive patients were compared with those who were negatve. Also, vitamin D levels of positive patients who survived were compared with those who died of COVID-19. Data of PCR-positive patients who had not been inpateints at the study centers within the study period was excluded.
Data was analysed using SPSS21. Normality of continuous variables was tested using the Shapiro-Wilk test. Vitamin D levels were found to be non-normally distributed. Descriptive statistics were presented as median Q1-Q3 (Q1: first quartile, Q3: third quartile) for continuous variables, and frequencies and percentages for categorical variables. Mann-Whitney U test was used for comparison between the groups. The level of statistical significance was set at p<0.05.
Of the 2,105 patients whose data was retrieved, 212(10%) were positive for COVID-19, while 1,893(90%) were negative. Among the positive patients, 89(42%) were men and 123(58%) were women. The overall median age was 45 years (Q1-Q3: 35-56 years). Among the negative patients, 726(38.4%) were men and 1,167(61.6%) were women. The overall median age of 42 (Q1-Q3: 30-56 years). Covid-19-positive women were aged significantly higher than those who were negative (p=0.007). All other age comparisons were not significant (p>0.05). Among the negative patients, 174(9.19 %), and among the positive patients, 20(9.43%) were on vitamin D supplementation.
Vitamin D level was not significantly different between the positive and negative patients (p>0.05) (Table).
Among the positive patients, 2(0.9%) did not have new admissions to the designated centers and their data was excluded, 206(97.2%) survived and 4(1.9%) died. There was no significant difference in vitamin D levels between those who survived and those who died (p>0.05).
The study fund no significant difference between the vitamin D levels of patients who tested PCR-positive and negative for SARS-CoV-2 infection, as well as between those who survived COVID-19 and those died because of COVID-19. A statistically significant association between age and COVID-19 positivity was observed in females, but not in the male gender.
Clinical observations indicated that advanced age and male gender increased the risk of COVID-19.4,14 Different from these observations, most patients in the current study were females, and, similar to these observations, COVID-19-positive females were older. The discrepancies in the current results might be due to the study's small smaple size.
Different studies indicated that vitamin D could positively affect acute RTIs by increasing the production of antimicrobial peptides in the respiratory epithelium and reducing inflammation related to the disease. Vitamin D may also have immune-supporting properties through modulation of the immune system, which could affect the severity of the response to COVID-19, and, therefore, vitamin D deficiency may be associated with COVID-19-related mortality. Vitamin D levels differ across the world, but even the more sunny countries in southern Europe experienced seriously high incidence of COVID-19 and related mortalities.15-17
Vitamin D levels were found to be low in different studies conducted in Turkey, which is also located in the southern part of the northern hemisphere.10 Therefore, it is crucial to investigate the relationship between COVID-19 and vitamin D levels.
There are conflicting results in literature about the vitamin D level status of COVID-19 patients, with some indicating lower vitamin D levels in patients with COVID-19, while other reporting otherwise.18-22 The present study could not find a relationship between vitamin D levels and COVID-19.
The effectiveness of supplemental vitamin D in preventing RTIs has been reported in different studies.6,12 Additionally, deficiency of vitamin D and the presence of some metabolic diseases can adversely affect the prognosis of COVID-19. It is evident that more comprehensive studies are needed to assess their effects on the impaired immunological system and prognosis in COVID-19.23 A study suggested vitamin D as an immunomodulatory agent that confers protection against the severity of COVID-19 and that serum levels of 25(OH)D should be maintained within the range of 40-60ng/mL to minimise the risk and severity of COVID-19.20 A study conducted in patients with COVID-19 reported a more frequent occurrence of pneumonia in patients without vitamin D supplementation 6 months before diagnosing COVID-19.24 The present study could not find a relationship between vitamin D supplementation and the disease.
In the present study, the mean vitamin D levels were low in both PCR-positive and PCR-negative cases, and no significant difference was found between the groups. The current study has an important limitation as the vitamin D level had been tested much earlier than the diagnosis of COVID 19.
Considering the varying results reported by literature, large-scale, community-based studies are needed to investigate the impact of vitamin D on COVID-19 prevention, prognosis, and survival.
No significant relationship was found between low vitamin D levels and COVID-19 and related deaths.
Acknowledgement: We would like to thank Editage (http://www.editage.com) for English language editing, Vademecum (http://www.vademecumonline.com.tr) for its online support and ARGEV (The Turkish Family Medicine Research Development and Education Foundation http://www.argev.org.tr) for providing education before the study and for their cooperation, and our colleagues and family physicians who have contributed to this study by participating in all the districts of Bursa province.
Conflict of Interest: None.
Source of Funding: None.
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