Vitamin D has been identified by the European Food Safety Authority (EFSA) as having sufficient evidence for a causal relationship between intake and optimal immune system function
26-29.
Vitamin D inhibits SARS-CoV-2 replication
in vitro16,23, mitigates lung inflammation, damage, and lethality in mice with an MHV-3 model for β-CoV respiratory infections
16,23, reduces SARS-CoV-2 replication in nasal epithelial cells via increased type I interferon expression
19, downregulates proinflammatory cytokines IL-1β and TNF-α in SARS-CoV-2 spike protein-stimulated cells
15, attenuates nucleocapsid protein-induced hyperinflammation by inactivating the NLRP3 inflammasome through the VDR-BRCC3 signaling pathway
20, may be neuroprotective by protecting the blood-brain barrier, reducing neuroinflammation, and via immunomodulatory effects
30, may mitigate hyperinflammation and cytokine storm by upregulating TLR10 expression which downregulates proinflammatory cytokines
12, downregulates ACE2 and TMPRSS2 in human trophoblasts and minimizes spike protein-induced inflammation
18, may minimize cytokine storm by dampening excessive cytokine production
2, may suppress post-entry viral replication and minimize cathepsin-L-dependent entry via LL-37 induction
11, and minimizes platelet aggregation mediated by SARS-CoV-2 spike protein via inhibiting integrin αIIbβ3 outside-in signaling
14.
Cholecalciferol and calcifediol directly bind two allosteric pockets on the SARS-CoV-2 Spike RBD, bias the trimer toward a closed state, weaken ACE2 engagement, and reduce viral entry in cell models
1.
Vitamin D improves regulatory immune cell levels and control of proinflammatory cytokines in severe COVID-19
31.
Calcifediol inhibits SARS-CoV-2 papain-like protease (PLpro), a critical enzyme for viral replication
13.
Symptomatic COVID-19 is associated with a lower frequency of natural killer (NK) cells and vitamin D has been shown to improve NK cell activity
32,33.
