According to our study, COVID-19 patients with vitamin D deficiency (a serum level of less than 20 ng/dl) were about twice as much at risk for ICU hospitalization and death, even after adjusting the statistical model for age and gender.
In a recent study, linking the data from UK Biobank to COVID-19 test results revealed an association between vitamin D and COVID-19 infection which was not significant after adjustment for confounders. Among the 348,598 participants, 449 tested positive for COVID-19. The median serum 25(OH)D concentration was lower in COVID-19 positive patients. However, after performing univariable logistic regression analysis adjusted for confounding factors, the authors found no strong evidence to support a potential protective role of vitamin D against COVID-19 infection.(11)
Another retrospective multicentral study of 212 cases with laboratory-confirmed infection of SARS-CoV-2 showed that serum 25(OH)D level was lowest in critical cases, and a decrease in serum 25(OH)D level could worsen clinical outcomes of the patients.(12)
Meltzer et al. studied the documents of 4,314 patients tested for COVID-19. Of those, 499 had had a vitamin D result during the last year, and 178 (36%) cases were diagnosed as vitamin D deficient. The multivariable analysis suggested that persons with vitamin D deficiency were at a substantially higher risk of testing positive for COVID-19.(13)
Several possible mechanisms can link vitamin D to COVID-19. Firstly, it is now clear that vitamin D plays important roles in the modulation of the immune system and its low level is associated with both increased autoimmune and infectious diseases. Calcitriol, the active form of vitamin D, has its own nuclear receptor (VDR) trough which can alter gene expression. To our knowledge, immunologic cells are capable of synthesizing the active calcitriol, and the VDRs have been found in these cells as well. Therefore, vitamin D can even act in a paracrine or autocrine manner to affect immunity.(14)
Vitamin D improves physical protection against pathogens by maintaining junction integrity.(15) It also enhances cellular innate immunity partly through the induction of antimicrobial peptides (such as cathelicidin and defensins) as well as reducing the cytokine storm which has been widely observed in COVID-19 patients.(16) Vitamin D is a modulator of adaptive immunity via suppressing responses mediated by the T helper cells type1 (Th1), promoting cytokine production by the T helper cells type 2 (Th2), and improving induction of the T regulatory cells, thereby inhibiting inflammatory processes.(17) It therefore comes as no surprise why many documents depict an association between lower vitamin D levels and a higher rate of upper respiratory tract infection, influenza, bacterial vaginosis, HIV and other viral or microbial infections.(18–22)
A recent study claimed that subtropical and mid-latitude countries are most affected by COVID-19. This finding, if correct, might be partly explained by the higher prevalence of vitamin D deficiency in these geographical regions.(23) Furthermore, the seasonal fluctuation of serum vitamin D level might be responsible for the higher risk of respiratory infections in fall and winter.(24)
Another link between COVID-19 and vitamin D is the rennin angiotensin system (RAS). It seems that angiotensin converting enzyme 2 (ACE2) is the functional receptor of SARS-CoV-2 to which the virus gets attached and then penetrates into the host cell. During the SARS-CoV-2 infection, tissues, especially lungs, face a loss in ACE2 function followed by an increase in the concentration of angiotensin II which finally leads to increasing alveolar permeability and accelerating lung damage.(25) Interestingly, vitamin D can increase the expression of ACE2 mRNA which can act as a double-edged sword; on the one hand, it can increase the number of receptors for the virus to enter the cells and on the other hand it can protect the pulmonary tissue from damage by saving the function of ACE2.
A Vitamin D concentration was among the parameters with the significant diagnostic accuracy for the early detection of COVID-19 death and requiring invasive mechanical ventilation. Vitamin D seems to have the same or more predictive value than LDH, ESR and CRP for COVID-19 poor outcomes. However, it has lower predictive ability compared to lymphocyte count, creatinine, and CPK. Previously, independent parameters such as underlying comorbidity, older age, higher LDH and lower lymphocyte count were used to develop a scoring model for predicting the progression of COVID-19.(26)
In conclusion, the present study showed that vitamin D deficiency can be considered as a predictor for poor outcomes and mortality in COVID-19 patients. Therefore, taking vitamin D supplements according to the prophylactic or treatment protocols is recommended as before. In addition, it is suggested that serum vitamin D status be checked in all COVID-19 patients on admission and appropriate action be taken to correct the possible deficiency or insufficiency.