Abstract: (2020) 18:322 Xu et al. J Transl Med https://doi.org/10.1186/s12967-020-02488-5 Journal of Translational Medicine Open Access REVIEW The importance of vitamin d metabolism as a potential prophylactic, immunoregulatory and neuroprotective treatment for COVID‑19 Yi Xu1,2,3* , David J. Baylink2, Chien‑Shing Chen1,3, Mark E. Reeves1,3, Jeffrey Xiao2, Curtis Lacy1, Eric Lau1 and Huynh Cao1,3 Abstract The coronavirus disease 2019 (COVID-19) pandemic has led to a declaration of a Public Health Emergency of Interna‑ tional Concern by the World Health Organization. As of May 18, 2020, there have been more than 4.7 million cases and over 316,000 deaths worldwide. COVID-19 is caused by a highly infectious novel coronavirus known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), leading to an acute infectious disease with mild-to-severe clini‑ cal symptoms such as flu-like symptoms, fever, headache, dry cough, muscle pain, loss of smell and taste, increased shortness of breath, bilateral viral pneumonia, conjunctivitis, acute respiratory distress syndromes, respiratory failure, cytokine release syndrome (CRS), sepsis, etc. While physicians and scientists have yet to discover a treatment, it is imperative that we urgently address 2 questions: how to prevent infection in immunologically naive individuals and how to treat severe symptoms such as CRS, acute respiratory failure, and the loss of somatosensation. Previous studies from the 1918 influenza pandemic have suggested vitamin D’s non-classical role in reducing lethal pneumonia and case fatality rates. Recent clinical trials also reported that vitamin D supplementation can reduce incidence of acute respiratory infection and the severity of respiratory tract diseases in adults and children. According to our literature search, there are no similar findings of clinical trials that have been published as of July 1st, 2020, in relation to the supplementation of vitamin D in the potential prevention and treatment for COVID-19. In this review, we summarize the potential role of vitamin D extra-renal metabolism in the prevention and treatment of the SARS-CoV-2 infection, helping to bring us slightly closer to fulfilling that goal. We will focus on 3 major topics here: 1. Vitamin D might aid in preventing SARS-CoV-2 infection: • Vitamin D: Overview of Renal and Extra-renal metabolism and regulation. • Vitamin D: Overview of molecular mechanism and multifaceted functions beyond skeletal homeostasis. • Vitamin D: Overview of local immunomodulation in human infectious diseases. – Anti-viral infection. – Anti-malaria and anti-systemic lupus erythematosus (SLE). *Correspondence: dyxu@llu.edu 1 Division of Hematology and Oncology, Department of Medicine, Loma Linda University, Loma Linda, California, USA Full list of author information is available at the end of the article © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your..