Vitamin D Deficiency and COVID-19: A Biological Database Study on Pathways and Gene-Disease Associations.

Vitamin D (VD) is a fat-soluble vitamin, and pivotal for maintaining health. Several genetic markers have been related to a deficient VD status; these markers could confer an increased risk to develop osteoporosis and other chronic diseases. A VD deficiency could also be a determinant of a severe COVID-19 disease. This study aimed to interrogate genetic/biological databases on the biological implications of a VD deficiency and its association with diseases, to further explore its link with COVID-19. The genetic variants of both a VD deficiency and COVID-19 were identified in the genome-wide association studies (GWAS) catalog and other sources. We conducted enrichment analyses (considering corrected p-values < 0.05 as statistically significant) of the pathways, and gene-disease associations using tools, such as FUMA, REVIGO, DAVID and DisGeNET, and databases, such as the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). There were 26 and 46 genes associated with a VD deficiency and COVID-19, respectively. However, there were no genes shared between the two. Genes related to a VD deficiency were involved in the metabolism of carbohydrates, retinol, drugs and xenobiotics, and were associated with the metabolic syndrome and related factors (obesity, hypertension and diabetes mellitus), as well as with neoplasms. There were few enriched pathways and disease connections for the COVID-19-related genes, among which some of the aforementioned comorbidities were also present. In conclusion, genetic factors that influence the VD levels in the body are most prominently associated with nutritional and metabolic diseases. A VD deficiency in high-risk populations could be therefore relevant in a severe COVID-19, underlining the need to examine whether a VD supplementation could reduce the severity of this disease.

Vitamin D in Human Immunodeficiency Virus Infection: Influence on Immunity and Disease.

People living with human immunodeficiency virus (HIV) infection typically have hypovitaminosis D, which is linked to a large number of pathologies, including immune disorders and infectious diseases. Vitamin D (VitD) is a key regulator of host defense against infections by activating genes and pathways that enhance innate and adaptive immunity. VitD mediates its biological effects by binding to the Vitamin D receptor (VDR), and activating and regulating multiple cellular pathways. Single nucleotide polymorphisms in genes from those pathways have been associated with protection from HIV-1 infection. High levels of VitD and VDR expression are also associated with natural resistance to HIV-1 infection. Conversely, VitD deficiency is linked to more inflammation and immune activation, low peripheral blood CD4+ T-cells, faster progression of HIV disease, and shorter survival time in HIV-infected patients. VitD supplementation and restoration to normal values in HIV-infected patients may improve immunologic recovery during combination antiretroviral therapy, reduce levels of inflammation and immune activation, and increase immunity against pathogens. Additionally, VitD may protect against the development of immune reconstitution inflammatory syndrome events, pulmonary tuberculosis, and mortality among HIV-infected patients. In summary, this review suggests that VitD deficiency may contribute to the pathogenesis of HIV infection. Also, VitD supplementation seems to reverse some alterations of the immune system, supporting the use of VitD supplementation as prophylaxis, especially in individuals with more severe VitD deficiency.