COVID-19 and Vitamin D: A lesson from the skin

Abstract

The negative outcomes of COVID-19 diseases respiratory distress (ARDS) and the damage to other organs are secondary to a "cytokine storm" and to the attendant oxidative stress. Active hydroxyl forms of vitamin D are anti-inflammatory, induce antioxidative responses, and stimulate innate immunity against infectious agents. These properties are shared by calcitriol and the CYP11A1-generated non-calcemic hydroxyderivatives. They inhibit the production of pro-inflammatory cytokines, downregulate NF-κΒ, show inverse agonism on RORγ and counteract oxidative stress through the activation of NRF-2. Therefore, a direct delivery of hydroxyderivatives of vitamin D deserves consideration in the treatment of COVID-19 or ARDS of different aetiology. We also recommend treatment of COVID-19 patients with high-dose vitamin D since populations most vulnerable to this disease are likely vitamin D deficient and patients are already under supervision in the clinics. We hypothesize that different routes of delivery (oral and parenteral) will have different impact on the final outcome.

Keywords: COVID-19; SARS-CoV-2; cytokine storm; oxidative stress; vitamin D; vitamin D-hydroxyderivatives.

FIGURE 1

Vitamin D as the solution to the COVID‐19 illness. (A) Hydroxyderivatives of vitamin D₃, by inhibition of cytokine storm and oxidative stress, will attenuate ARDS and multiorgan failure induced by COVID‐19. (B) Mechanism of action of canonical and non‐canonical vitamin D‐hydroxyderivatives. Vitamin D signalling in mononuclear cells downregulates inflammatory genes and suppresses oxidative stress. VDR, vitamin D receptor; RXR, retinoid X receptor; ROR, retinoic acid orphan receptor, RORE, ROR response element; ARE, antioxidant response element; VDRE, vitamin D response element; NRF2, transcription factor NF‐E2‐related factor 2. (C) Different routes of vitamin D delivery will impact vitamin D activation pattern