Vitamin D deficiency in association with endothelial dysfunction: Implications for patients with COVID-19

Abstract

There is emerging evidence to suggest that vitamin D deficiency is associated with adverse outcomes in COVID-19 patients. Conversely, vitamin D supplementation protects against an initial alveolar diffuse damage of COVID-19 becoming progressively worse. The mechanisms by which vitamin D deficiency exacerbates COVID-19 pneumonia remain poorly understood. In this review we describe the rationale of the putative role of endothelial dysfunction in this event. Herein, we will briefly review (1) anti-inflammatory and anti-thrombotic effects of vitamin D, (2) vitamin D receptor and vitamin D receptor ligand, (3) protective role of vitamin D against endothelial dysfunction, (4) risk of vitamin D deficiency, (5) vitamin D deficiency in association with endothelial dysfunction, (6) the characteristics of vitamin D relevant to COVID-19, (7) the role of vitamin D on innate and adaptive response, (8) biomarkers of endothelial cell activation contributing to cytokine storm, and (9) the bidirectional relationship between inflammation and homeostasis. Finally, we hypothesize that endothelial dysfunction relevant to vitamin D deficiency results from decreased binding of the vitamin D receptor with its ligand on the vascular endothelium and that it may be immune-mediated via increased interferon 1 α. A possible sequence of events may be described as (1) angiotensin II converting enzyme-related initial endothelial injury followed by vitamin D receptor-related endothelial dysfunction, (2) endothelial lesions deteriorating to endothelialitis, coagulopathy and thrombosis, and (3) vascular damage exacerbating pulmonary pathology and making patients with vitamin D deficiency vulnerable to death.

The Relationship Between Vitamin D and Infections Including COVID-19: Any Hopes?

“…160 The damaged respiratory endothelium during the entrance of SARS-CoV-2 through ACE2 receptors leads to endothelial dysfunction that in turn interferes with the binding of inadequately present vitamin D to its receptor (VDR), resulting in further progression of the inflammatory process and increased risk of severity in COVID-19. 162 Lately, several researchers have confirmed the positive effects of GSH, that acts as a potent antioxidant, along with its precursor, L-cysteine, on vitamin D metabolism. 41 Thus individuals with depleted GSH become less able to overcome the oxidative stress that develops during infections.…”

Role of endothelial cell receptors in the context of SARS-CoV-2 infection (COVID-19)

“…Conversely, EC dysfunction resulting from angiotensin-converting enzyme 2 (ACE2) and vitamin D receptors contributes to coronavirus disease 2019 (COVID-19)-associated vascular inflammation and coagulopathy. 1,2 Studying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a primate model, Koo et al showed that the development of COVID-19 caused acute interstitial pneumonia with endotheliitis in the lungs. 3 These findings strengthen the implications of EC dysfunction in COVID-19.…”

Vitamin D and Sars-Cov-2: A Review of the Literature

“…Furthermore, several authors underline the association between low levels of vitamin D and pulmonary pathologies 26 , chronic pathologies associated with metabolic syndrome 4 , vascular damage 27 , thrombotic episodes 28 confirming that this deficiency associated with these conditions involves a serious risk for the development of SARS infection. Cov-2 29 .…”