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

Int J Mol Sci. 2022 Nov 17;23(22):14256. doi: 10.3390/ijms232214256.


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.

Keywords: COVID-19; SARS-CoV-2; computational biology; genes; nutrition; vitamin D.

MeSH terms

  • COVID-19* / genetics
  • Genome-Wide Association Study
  • Humans
  • Vitamin D / genetics
  • Vitamin D / metabolism
  • Vitamin D Deficiency* / complications
  • Vitamin D Deficiency* / epidemiology
  • Vitamin D Deficiency* / genetics
  • Vitamins


  • Vitamin D
  • Vitamins