Vitamin D deficiency and co-morbidities in COVID-19 patients – A fatal relationship?

Abstract

Infections of the respiratory tract are more frequent in the winter months and especially in the northern latitudes than they are in summer [1]. This obviously also applies to the COVID-19 infectious disease that briefly spread all over the world in the winter months and became a pandemic [2,3]. A common feature of the winter months and the inhabitants of all countries north of the 42nd parallel is a hypovitaminosis D that frequently occurs during this period [4]. In addition during cold temperature the virus will be more easily transmitted. This raises the question of whether an inadequate vitamin D supply has an influence on the progression and severity of COVID-19 disease. A low vitamin D status, measured as the plasma level of the transport form of vitamin D, 25(OH)D,is widespread worldwide and is mainly found in regions of northern latitudes, but also in southern countries [5]. In Europe, vitamin D deficiency is widely prevalent during the winter months and affects mainly elderly people and migrants. In Scandinavia only 5% of the population is affected by a low vitamin D status, in Germany, France and Italy more than 25%, particularly older people e.g. in Austria up to 90% of senior citizens [6,7]. In Scandinavian countries, the low incidence of vitamin D deficiency may be due to the traditional consumption of cod liver oil rich in vitamin D and A or to genetic factors resulting in higher synthesis of vitamin D in the epidermal layer [8]. Taken together, low vitamin D status is common in Europe with the exception of the Scandinavian countries. The calculated COVID-19 mortality rate from 12 European countries shows a significant (P = .046) inverse correlation with the mean 25(OH)D plasma concentration [9]. This raises the question whether insufficient vitamin D supply has an influence on the course of COVID-19 disease? An analysis of the distribution of Covid-19 infections showed a correlation between geographical location (30–50° N+), mean temperature between 5–11 °C and low humidity [10]. In a retrospective cohort study (1382 hospitalized patients) 326 died, Among them 70.6% were black patients. However, black race was not independently associated with higher mortality [11]. An excess mortality (2 to sixfold have been described in African-Americans with average latitudes of their state of residence in higher latitudes (> 40) [12]. The mortality of COVID-19 (cases/ million population) shows a clear dependence on latitude. Below latitude 35, mortality decreases markedly [13]. Indeed, there are exceptions e.g. Brazil (tenfold higher than all other latin American countries – except mexico), however, the management of the pandemic may increase infection risk. 1.1. Vitamin D effects The skeletal and extra skeletal effects of vitamin D have recently been described in an extensive review [14]. Vitamin D exerts a genomic and non-genomic effect on gene expression. The genomic effect is mediated by the nuclear vitamin D receptor (VDR), which acts as a ligand activated transcription factor. The active form 1,25(OH)2D binds to the VDR and in most cases heterodimerizes with the retinoid X receptor (RXR), whose ligand is one of the active metabolites of vitamin A, 9-cis retinoic acid. The interaction of this complex with the vitamin D responsive element can regulate the expression of target genes either positively or negatively [15]. The non-genomic effects involve the activation of a variety of signaling molecules that interact with Vitamin D responsive element (VDRE) in the promoter regions of vitamin D dependent genes [16]. Vitamins A and D are also of particlular importance for the barrier function of mucous membranes in the respiratory tract [17,18].