The activation of the VDR signaling pathway may generate beneficial effects by, decreasing the cytokine/chemokine storm, producing a shift from a Th1 and Th17 phenotype towards adaptive immune responses with an amplified Th2 phenotype; regulating the renin–angiotensin–bradykinin system (RAAS); modulate neutrophil activity and maintain the integrity of the pulmonary epithelial barrier; stimulating epithelial repair and directly and indirectly decreasing the increased coagulability and prothrombotic tendency associated with severe COVID-19 and its complications. This evidence concerns the gene VDR and COVID-19.