A Randomized trial to determine the effect of vitamin D and zinc supplementation for improving treatment outcomes among COVID-19 patients in Mumbai, India

The COVID-19 pandemic has an unprecedented scale of spread. There is urgent need for effective treatments, and research has focused on development of antiviral drugs and vaccines. However, since host immune response is a critical determinant of disease severity for life-threatening infections, interventions that modify deleterious host responses (for e.g. immune activation, endothelial dysfunction, micro-vascular injury and pro-coagulant responses) may also play a critical role in decreasing progression to severe and fatal COVID-19. Micronutrient deficiencies, particularly vitamin D and zinc, have been associated with dysregulation of these host responses and may play an important role in COVID-19. Nutritional status is critical especially in older individuals and those with chronic disease including diabetes and cardiovascular disease, in whom COVID-19 is often more severe. While supplementation is important in other infections, there are no well-designed studies on the potential effect of such supplements in COVID-19. In line with CIHR's call for testing therapeutics for COVID-19, we propose a 2x2 factorial randomized trial to examine the effectiveness of vitamin D and zinc supplements as immune-based therapy among 700 patients in Mumbai, India. We will also examine the immunological response to COVID-19 and the effect of the intervention on specific biomarkers of immune and endothelial activation (e.g. Angiopoietin-2) that are independent and quantitative predictors of severity and mortality in other severe infections (e.g. sepsis, pneumonia).