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

Vitamin D is proposed to have a potential role in the pathogenicity, clinical presentation, prognosis, complications, and treatment of several diseases. In addition to its well-known role in calcium metabolism, vitamin D regulates both innate and adaptive immunity, and subsequently modulates the antiviral and antibacterial inflammatory immune responses. In view of the emerging coronavirus disease 2019 (COVID-19) pandemic, searching for potential therapeutic and protective strategies is of urgent interest, and vitamin D is one of the promising agents in this field. In this review, we present data from literature that supports the promising role of vitamin D in treatment and/or prevention of several infections including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This review summarizes vitamin D metabolism and its role in inflammation, thrombosis and immune regulation. It also reviews, in short, the role of vitamin D and the impact of its deficiency in several infections namely tuberculosis, influenza, human immunodeficiency virus (HIV), and SARS-CoV-2. Considering the roles of vitamin D on immune modulation, controlling of thrombosis, and attacking several microorganisms, the current review will elaborate on the association between these salient roles of vitamin D and the pathogenicity of various infectious agents including COVID-19. Consequently, the comprehensive finding of the current review shows a possible significant impact of vitamin D supplement as a hope in preventing, treating, and/or improving the progression of certain infections, specifically during the worldwide attempts to fight against the COVID-19 pandemic and minimize the severity of health complications encountered accordingly. In addition, avoiding a status of vitamin D deficiency to obtain its positive effects on the immune system and its protective mechanism during infections will be a general benefit overall.

Ex vivo evaluation of antifibrotic compounds in skin scarring: EGCG and silencing of PAI-1 independently inhibit growth and induce keloid shrinkage.

Keloid disease (KD) is a common fibroproliferative disorder of unknown etiopathogenesis. Its unique occurrence in human skin and lack of animal models pose challenges for KD research. The lack of a suitable model in KD and over-reliance on cell culture has hampered the progress in developing new treatments. Therefore, we evaluated the effect of two promising candidate antifibrotic therapies: (-)-epigallocatechin-3-gallate (EGCG) and plasminogen activator inhibitor-1 (PAI-1) silencing in a long-term human keloid organ culture (OC). Four millimeters of air-liquid interface (ALI) keloid explants on collagen gel matrix in serum-free medium (n=8 cases) were treated with different modalities (EGCG treatment; PAI-1 knockdown by short interfering RNA (siRNA) and application of dexamethasone (DEX) as control). Normal skin (n=6) was used as control (only for D0 keloid-untreated comparison). Besides routine histology and quantitative (immuno-) histomorphometry, the key phenotypic and growth parameters of KD were assessed. Results demonstrated that EGCG reduced keloid volume significantly (40% by week 4), increased apoptosis (≥40% from weeks 1 to 4), and decreased proliferation (≤17% in week 2). EGCG induced epidermal shrinkage, reduced collagen-I and -III at mRNA and protein levels, depleted 98% of keloid-associated mast cells, and reduced the percentage of both cellularity and blood vessel count by week 4. Knockdown of PAI-1 significantly reduced keloid volume by 28% in week 4, respectively, and reduced collagen-I and -III at both mRNA and protein levels. As expected, DEX increased keloid apoptosis, decreased keloid proliferation, and collagen synthesis, but induced connective tissue growth factor overexpression. In conclusion, using keloid OC model, we provide the first functional evidence for testing candidate antifibrotic compounds in KD. We show that EGCG and PAI-1 silencing effectively inhibits growth and induces shrinkage of human keloid tissue in situ. Therefore, the application of EGCG, PAI-1 silencing, and other emerging compounds tested using this model may provide effective treatment and potentially aid in the prevention of recurrence of KD following surgery.