The Perfect Storm Review: Immune Dysregulation in Severe COVID-19 and the Possible Role of Mast Cell-Vitamin D Interactions

Abstract

COVID-19 is caused by a Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) and has two spike subunits on the envelope of SARS-CoV-2, S1 and S2, where S1 binds to the Angiotensin Converting Enzyme (ACE-2), a receptor on the host cells and S2 binds to the cell surface membrane. Different immune responses to the virus are apparent, from asymptomatic to severe respiratory distress, organ failure and ultimately death. Immune responses without hyper-inflammation are essential to successful viral resolution. Pathological and environmental factors drive the immunological repertoire, in response to the virus, influencing innate immune cell activation, cytokine-balance and T cell differentiation. This is determined by age, comorbidity, Vitamin D status and ethnicity related factors. Homeostasis of the immune system plays an important role in the development of COVID-19 pneumonia. Mast cell activation and release of histamine is important to the cytokine driven T-cell differentiation as the adaptive response. This review combines the relative effects of UV-index-related Vitamin-D synthesis with immune status. Innate immune responses, T cell differentiation and renin/angiotensin system are different in patients affected by COVID-19 and their different outcomes are explored.