Discussion
Our study evaluated the vitamin D deficiency prevalence and the association between vitamin D deficiency and clinical and inflammatory markers in our patients hospitalized for COVID-19 infection. To the best of our knowledge, we have not found any study on vitamin D levels in pediatric patients diagnosed with COVID-19 in our literature review of resources in English. We aim to investigate whether children diagnosed with COVID-19 had vitamin D deficiency as well as the realationship between vitamin D deficiency and clinical outcomes.
Although there are no adequate studies on vitamin D levels and its effects in children with COVID-19, there are several studies evaluated the relationship between other respiratory pathogens and vitamin D. In some clinical studies, vitamin D has been shown to protect children from lung infection. Children with vitamin D deficiency or insufficiency are more susceptible to respiratory infection (13). A meta-analysis and systematic review of 25 randomized controlled trials by Martineau et al. showed that vitamin D generally protects against acute respiratory infection (14). In an important study covering 1582 people by Li et al. with aim of determining the relationship between 25(OH)D in children and pulmonary infection, the community-acquired pneumonia group displayed a lower value than the control group, and there were also significant differences between the pneumonia group and pneumonia-derived sepsis group ( p  <0.001), and there was association between lower serum 25(OH)D level and more serious symptoms (15).
Daneshkhah et al. observed that high CRP was inversely correlated with 25(OH)D, and they thought vitamin D to have a possible role in reduction of complications caused by abnormal inflammation and cytokine storm given the CRP as a marker for cytokine storm and considering its association with vitamin D deficiency (16). Some previous studies found negative correlation between 25(OH) D vitamin level and pneumonia severity, CRP level, increased risk of sepsis, ARDS risk and increased production of proinflammatory cytokines such as IL-6 (17-21). In the present study, a negative correlation was found between vitamin D level and fever symptom (p = 0.023), but there was no significant finding in terms of CRP level and clinical severity.
In a study conducted by Alipio M et al. observed that vitamin D level was low or insufficient in 74.1% of patients diagnosed with COVID 19 and also found a statistically significant difference between serum 25(OH)D level and clinical outcomes (p <0.001) (22). In another study of Lau et al. regarding the relationship between vitamin D deficiency and the severity of COVID-19 disease in adult age group, low levels of vitamin D were found in 75% of the cases and 84.6% of the patients in intensive care unit (23). In a study conducted on adults, Raharusa et al. found deficient or insufficient levels of vitamin D in 47.3% of 780 patients diagnosed with COVID-19. Vitamin D was insufficient in 27.3% of them and deficient in 20% of them. They observed mortality in 49.1% of vitamin D insufficient cases, 46.7% of deficient ones and 4.1% of normal ones, and found statistically significant results between vitamin D level and mortality (p <0.001). However, the comorbid factors concomitant with the majority of those with deficient and insufficient vitamin D levels in their studies make it difficult to evaluate the relationship between mortality and vitamin D alone (24). In our study, 72.5% of our cases were vitamin D deficient or insufficient, and 2 patients (100%) in need of treatment in the intensive care unit had the vitamin D level of below 10 ng/ml, and had comorbid diseases, but none of them had mortality. In our study, the distribution of disease severity according to vitamin D levels was not found significantly different (p = 0.097). Yet, although the virulence mechanisms related to COVID-19 are not fully characterized, the fact that clinical severity and mortality rate of the disease generally progress better in children compared to adults suggests that it may be due to Ace 2 receptor count and cytokine storm being less than that of adults depending on immunological response. When COVID 19 diagnosed childrens who had deficient and insufficient level of vitamin D (group 1) and covid 19 diagnosed childrens who had normal level of vitamin (group 2) compared at admission, Group 1 had significantly higher fever symptom (34.5%, 10) than Group 2 (0%) (p = 0.038). A negative correlation was found between vitamin D level and fever symptom (p = 0.023), but there was no significant finding in terms of CRP level and clinical severity.
A study conducted by Ilie et al., found that average vitamin D levels in each country and the COVID-19 cases were negatively correlated with the number of deaths caused by COVID-19 (25). Since there were no patients in our study who died, there was no evaluation of the relationship between vitamin D levels and mortality.
In conclusion, our study is the first to evaluate vitamin D levels and its relationship with clinical findings in pediatric patients diagnosed with COVID-19. There are significantly lower levels of vitamin D in children with COVID-19 than those in the control group. This shows that vitamin D, which is effective in the immunological mechanism, also has an effect in the physiopathology of the disease. Vitamin D levels are associated with fever. Since we did not have any patients lost, their relationship with mortality could not be evaluated. More studies are needed in children for evaluation of the association between vitamin D with clinical and laboratory findings of the disease and its effect on mortality.