evidence: Vitamin D belongs to a group of fat-soluble vitamins with vitamin D3 being the major form in humans. The primary source is via cutaneous synthesis in response to sunlight, but it can also be ingested in the diet. The active vitamin D metabolite, 1,25-dihydroxyvitamin D (1,25(OH)2D), induces innate antiviral effector mechanisms and regulates inflammation in response to infection with rhinovirus, respiratory syncytial virus and influenza viruses (Fig. 1). The relevance of these actions for the host response to SARS-CoV-2 is supported by two lines of evidence. First, the vitamin D-inducible antimicrobial peptide cathelicidin LL-37 has been shown to inhibit SARS-CoV-2 attachment to host cells by blocking both the receptor-binding domain of the S1 subunit of the viral spike protein and the ligand-binding domain of the host-expressed viral entry receptor ACE2 (ref.1). Second, a study in transgenic mice expressing human ACE2 has shown that SARS-CoV-2 induces the expression of CYP27B1, which encodes the 1α-hydroxylase enzyme that catalyses the conversion of the major circulating metabolite 25-hydroxyvitamin D (25(OH)D) to 1,25(OH)2D (ref.2). Prophylactic administration of high-dose vitamin D3 increased the expression of IFNB and reduced inflammation in the lungs after SARS-CoV-2 infection, although this was not associated with a survival benefit2.