Vitamin D: A key player in COVID‐19 immunity and lessons from the pandemic to combat immune‐evasive variants https://link.springer.com/article/10.1007/s10787-024-01578-w As of July 2024 775,754,322 confirmed cases of COVID-19 13,578,710,228 vaccine doses had been administered It is unclear why some patients develop severe symptoms while others do not, literature suggests a role for vitamin D. Vitamin D plays a crucial role in the infection or in ameliorating the severity of symptoms. VDD is associated with increased hospitalization of severely ill patients and increased levels of COVID-19-caused mortality. The mechanism of action of vitamin D and vitamin D deficiency (VDD) is well understood. Vitamin D levels and genetic variations in the vitamin D receptor (VDR) gene significantly impact the severity and out- comes of COVID-19, especially in the infections caused by Delta and Omicron variants. Furthermore, VDD causes immune system dysregulation upon infection with SARS-CoV-2, indicating that vitamin D sufficiency is crucial in fighting against COVID-19 infection. Potential role as a prophylactic and treatment adjunct. Immunomodulatory and anti-inflammatory effects of vitamin D Ability to enhance the efficacy of new antiviral drugs Large- scale randomized trials are required to reach a definitive conclusion. Mechanisms of action Macrophages activated to produce defensive proteins and stimulate naïve T cells Activate T lymphocytes and mature B lymphocytes into plasma cells Prevents inflammation, vasoconstriction, and fibrosis of the lungs. Prevents excess release of cytokines from macrophages Prevents excessive CRP production in the liver Vit D can reduce viral replication Vitamin D can protect against ARDS, the main death-causing complication of COVID-19 Seven out of nine studies reviewed by Yisak https://pubmed.ncbi.nlm.nih.gov/33447107/ have indicated a crucial role in vitamin D status in COVID-19 infection, prognosis, and mortality. Vitamin D dose To decrease the risk of contracting a new infection, people at high risk of COVID-19 to take 10,000 IU d−1 of vitamin D for a few weeks, followed by 5000 IU d−1 to raise the concentrations of the active form of vitamin D. Blood levels Levels below 12 ng/mL indicate severe deficiency. Levels between 12 and 20 ng/mL suggest deficiency Treatment recommended for levels below 30 ng/mL Optimal levels are 30–60 ng/mL, Recommended prophylactic dose 0–1 years, 400 IU/day (10 mcg) over  1 year, 600 IU (15 mcg) over 8 years, half an adult dose Adults, 800– 2000 IU of cholecalciferol Routine toxicity monitoring is unnecessary for doses under 10,000 IU/day