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Definitive Evidence from Meta-Analysis and Trial Sequential Analysis (Italy) Various studies, a association between severe vitamin D deficiency and bad COVID-19 outcomes. Vitamin D plays a crucial role in immune function and inflammation. Recent data suggest a protective role of vitamin D against bad outcomes Nutraceutical approach Promote the immune response and reduce the inflammatory response Anti-inflammatory, antioxidant, and immunomodulatory properties of vitamin D Immune optimisation and immune boosting Vitamin D maintains pulmonary barrier function Determines the production of antimicrobial peptides Enhances neutrophil activity Shifts the adaptive immune response to a more T helper cell-2 type Anti-inflammatory effects of vitamin D Reduces the production of pro-inflammatory cytokines, such as IL-6, IL-8, IL-9, IL-12, TNF alfa, IFN gamma Increases production of anti-inflammatory cytokines, such as IL-4, IL-5, IL-10 Patients with a low baseline vitamin D, more benefit Reduce risk of asthma exacerbations Prevents acute respiratory infections, and reducing their complications COVID-19 and vitamin D (Co-VIVID study): a systematic review and meta-analysis of randomized controlled trials The rates of RT-CR positivity were significantly decreased in the intervention group as compared to the non-vitamin D groups (RR = ) Conclusively, COVID-19 patients supplemented with vitamin D, fewer rates of ICU admission, mortality events, and RT-PCR positivity. Meta-analysis and trial sequential analysis (TSA) Better explain the strength of association Protective role of vitamin D supplementation, and risk of mortality / admission to intensive care units We searched four databases on 20 September 2022. Screened the randomized clinical trials (RCTs) Assessed the risk of bias (how to adjust thresholds for significance in randomised clinical trials when the required sample size has not been reached) The pre-specified outcomes of interest Mortality and ICU admission 78 bibliographic citations Five RCTs were suitable for our analysis Results Vitamin D administration results in a decreased risk of death, Vitamin D administration results in a decreased risk of ICU admission, Protective role of vitamin D and ICU admission The TSA of the protective role of vitamin D and ICU admission showed that, since the pooling of the studies reached a definite sample size, the positive association is conclusive. The studies Effects of a 2-Week 5000 IU versus 1000 IU Vitamin D3 Supplementation on Recovery of Symptoms in Patients with Mild to Moderate Covid-19: A Randomized Clinical Trial (Saudi) Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study (Spain) Changes in the immune response against SARS-CoV-2 in individuals with severe COVID-19 treated with high dose of vitamin D (Spain) Effect of a Single High Dose of Vitamin D3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19 (Brazil) Calcifediol treatment and COVID-19-related outcomes (Spain) Medicines & Healthcare products Regulatory Agency 86% industry funded
