Table 2.

Potential effects of vitamin D on the risks and prognosis for patients with COVID-19

Categories	Possible effects	Mechanisms
Immune system	Modulating the risk of infection, attenuating excessive immune response	Innate immunity • Monocytes and macrophages: ↑proliferation [28], ↑antimicrobial peptides production (cathelicidins, defensins) [156], ↑autophagy [29] • Dendritic cells: ↓maturation [45], ↓MHC class II [45], ↓co-stimulatory molecules (CD40, CD80, CD86) [45], ↑inhibitory molecules (PD-L1)[157] Adaptive immunity • T cells: ↓proliferation [158], ↓Th1 (IFN-γ) [159] and Th17 (IL-17) [160] responses, ↑Th2 (IL-4, IL-5) [161] and Treg (IL-10) [157] responses • B cells: ↓proliferation [162], ↓differentiation into plasma cell [162], ↓Ig production (IgG, IgM) [163]
Inflammation	Anti-inflammation	↓TLR signaling [164], ↓NF-κB [165], ↓prostaglandins [166], ↑MAPK phosphatases [59], ↓proinflammatory cytokines (IL-6, TNF-α) [167], ↑inhibitory cytokines (IL-10, TGF-β) [157]
Fibrosis	Antifibrotic effect	↓Epithelial–mesenchymal transition [168], ↓fibroblast differentiation [169], ↑profibrotic factors (TGF-β, SERPINE1) [170], ↑antifibrotic factors (BMP-7, MMP-8, follistatin) [170], ↓collagen expression [170], ↓MCP-1 [171]
RAAS	Alleviating lung injury, improving outcome of preexisting CVD or reducing incident CVD	Classic pathway (ACE2/angiotensin-(1–7)/Mas receptor): ↑ACE2[21] Counter-regulatory pathway (angiotensin II/AT1R): ↓renin expression [21], ↓ACE [21], ↓angiotensin II expression [21]
ARDS	Reducing the risk of ARDS, promoting the recovery from lung injury	Epithelial barrier integrity: ↓extravascular lung water index [172], ↓pulmonary vascular permeability index [172] Epithelial injury: ↓RAGE (bronchoalveolar lavage fluid) [172], ↓protein permeability index [172] Inflammation: ↓TNF-α [172], ↓VEGF [172], ↓CXCL1 [172] Apoptosis: ↓soluble Fas ligand-mediated cell death [172] ↑Scratch wound healing [172]
Glucose metabolism	Improving outcomes of COVID-19 associated with hyperglycemia	T1DM: ↓insulitis [173], ↑β-cell survival [173], ↓disease onset [173], ↓disease progression [174] T2DM: ↑β-cell function [175], ↓islet inflammation [175], ↓islet RAAS components [176], ↓hyperglycemia [175], ↓disease progression [175]
CVD	Improving the prognosis of COVID-19	RAAS inhibition [65], ↓cardiac hypertrophy [177], ↑myocardial contractility [177], ↑endothelial function [177], ↓mortality [178]

ACE angiotensin-converting enzyme, ACE2 angiotensin-converting enzyme 2, AT1R angiotensin II type 1 receptor, ARDS acute respiratory distress syndrome, BMP-7 bone morphogenic protein-7, CD cluster of differentiation, COVID-19 coronavirus disease 2019, CVD cardiovascular disease, CXCL1 chemokine ligand 1, IFN interferon, Ig immunoglobulin, IL interleukin, MAPK mitogen-activated protein kinase, MCP-1 monocyte chemoattractant protein-1, MHC major histocompatibility complex, MMP-8 matrix metalloproteinase-8, NF-κB nuclear factor kappa-light-chain-enhancer of activated B cells, PD-L1 programmed death ligand-1, RAAS renin–angiotensin–aldosterone system, RAGE receptor for advanced glycation end products, T1DM and T2DM type 1 and type 2 diabetes mellitus, Th T helper cell, TLR toll-like receptor, Treg regulatory T cell, TGF-β transforming growth factor-β, TNF-α tumor necrosis factor-α, VEGF vascular endothelial growth factor