It is well established that the ubiquitously expressed master immune response transcription factor NF-κB is centrally involved in the pathogenesis of respiratory viral infections. [1] Indeed, COVID-19 is known to activate the NF-κB pathway that results in the upregulation of many inflammatory gene promoters. [2] It is postulated that this results from multiple catalytic interactions that occurs between the viral nucelocapsid proteins and NF-κB mediated immunomodulation. [3,4,5] This signaling dynamic is similar to the manner in which other highly fatal coronaviruses, such as MERS and SARS-COV, are known to take control of the NF-κB pathway. [6-8] The activation of the NF-kB pathway leads to the release of inflammatory mediators often linked to the systemic inflammatory response syndrome. [8]

Vitamin D3 (VD3) also is a regulator of NF-kB mediated cellular responses, It is known to inhibit the production of the proinflammatory cytokines TNFα, interleukins, and other key activators of the cellular immune defense. [9,10] VD3 promotes phenotypic shifting of lymphocytes towards an anti-inflammatory subsets. [11] Furthermore, data from clinical studies indicate that VD3 deficiency is clinically associated with increased susceptibility to respiratory viral infections and increased severity once infected. [12] In the case of respiratory syncytial virus, vitamin D3 increases synthesis of the NF-κB inhibitor, IκBα, resulting in decreased expression of pro-inflammatory genes… Continue reading.