Vitamin D had been known to affect the immune system and decrease the severity of respiratory tract infections [4–6]. Recent correlative analysis investigating the effect of mean serum levels on the COVID–19 occurrence/cases and deaths in European countries had indicated a tenuous negative (protective) covariation . The level of significance for correlation was borderline (p-value 0.0501 and 0.0534) as could be expected from countries included in the study being at different stages of the COVID–19 pandemic. For making the covariation analysis more robust, the data about cases and deaths per million population was also gathered from a later date, i.e., 12 May 2020, when the COVID–19 situation had stabilized and countries had passed the peak of the infection. It was found that the cases per million had registred about 1.2 fold (e.g., Iceland, Norway) to 4 fold increase (Ireland, Hungary, Turkey) while the death rates registered about 1.6 fold (e.g., Iceland) to 12.5 fold (e.g.,, Slovakia) increase (Table 1). The standard deviation of the data mean had also reduced (Table 1). The strength and significance of correlation changed both between vitamin D levels and cases per million (r(20): –0.4435; R2 = 0.1967; p-value: 0.0501 vs r(20): –0.5504; R2 = 0.3029; p-value: 0.0119) as well as between vitamin D and deaths per million (r(20): –0.4378; R2 = 0.1917; p-value: 0.0535 vs r(20): –0.3935; R2 = 0.1549; p-value: 0.0860). The exponential curve fitting of the data displayed still better correlation with cases per million (R2 = 0.3751) and deaths per million (R2 = 0.2754), as expected for a biological system with bottlenecks and required thresholds for seeing an effect (Figure 1). There is a possibility that there exists a cause and effect relationship.
The underlying differences in the population composition, age distribution, differential comorbidities distribution, medication practices, etc maybe some other confounding variables lowering the estimate of correlation. So, it may be surmised that higher vitamin D levels may be positively correlating with a reduced infection rate while its covariation with the adverse outcome may not be significantly correlated. It should be noted here that comprehensive vitamin D data is not available for the populations under study and within the countries different subgroups had been shown to have quite different levels of vitamin D ranging from deficiency to insufficiency . Particularly, children, women, aged, people of color are more prone to having vitamin D levels lower than means for the population. Complete dependence on mean values could be problematic in driving reliable inferences for protection from COVID–19. Studies involving target groups with known vitamin D levels would be able to shed light on the reliability of the the observed protective correlation and establishing the cause and effect relationship.
A study to evaluate the effect of vitamin D levels or supplementation may be planned for SARS- CoV–2 infection using carefully matched (i.e., age, basal vitamin D level, comorbidities, sex, genetic background, disease severity, etc) control and test groups. Alternatively, relatively reliable estimates can be made using collation of the required information from health systems if needed employing a surveillance questionnaire. The outcome of the suggested retrospective or exploratory studies would possibly provide a handle to limit the impact of COVID–19 in future waves of infection as well as the countries who are still in the early or middle phase of infections, e.g., Asian countries.
The current study indicated a stronger negative correlation between mean vitamin D levels of the European populations with COVID–19 cases per million in the populations than the association shown at an earlier stage of COVID–19 pandemic (R2 = 0.3751 vs R2 = 0.1967). However, the vitamin D levels correlation with deaths per million population among the studied countries seemed insignificant. As vitamin D is already known to boost the immune system and play an important role in reducing respiratory disease severity [4–6], it would be safe to assume its positive interaction with