Vitamin D Status and Immune-inflammatory Status in Different UK Populations With COVID-19 Infection

Overview

Hypothesis: Serum Vitamin D (25(OH)D) is significantly lower in severe versus non-severe COVID-19 infections and that this is a function of ethnicity. There is an association between vitamin D status and various cytokines (pro-inflammatory molecules). The primary objective of this research is to provide a snap shot of vitamin D status in patients from the South-East London area by age, sex, ethnicity and BMI and demonstrate ethnic differences in vitamin D status as well as its associations with severe vs non-severe COVID-19 infections. The secondary objective is to determine if there is an association between vitamin D status and various cytokines (pro-inflammatory molecules) and severity of disease.

Worldwide there has been over 6 million cases and 380,810 deaths from Coronavirus 2019 (COVID-19) (ECDC June 2020). According to the European Centre for Disease Prevention and Control (ECDC) risk factors for critical illness include elderly people above 70 years of age, and people with underlying conditions such as hypertension, diabetes, cardiovascular disease, chronic respiratory disease, immune compromised status and obesity (73.4% of critically ill patients with BMI 30-40). In addition, in the UK 32% of critically ill COVID-19 patients are of Black or Asian ethnic-minority background (ICNARC April 10th, 2020). There is therefore an urgent need to fully understand the risk factors for severe COVID-19 infection and find an effective treatment. In COVID-19 infection those patients that required intensive care treatment have high circulating cytokines and chemokines TNF-α, IL-2, IL-6, IL-7, IL-9, IL-17, IFN-γ, MCP-1 and MIP-1α. Severe COVID-19 infection appears therefore to be associated with a damaging hyperinflammation state. In addition to a dysregulated cytokine response there is also dysregulation of immune cell populations in COVID-19 infection. For example, there is low T regs, NK cell and CD8+ and CD4+ T cells in severe COVID-19 infection. Moreover, CD8+ T cells appear to be an independent predictor for COVID-19 severity and treatment efficacy. Other than genetic factors, e.g. HLA, which may predispose to severe COVID-19, vitamin D (25(OH)D) may be important for several reasons. Firstly because 25(OH)D inadequacy is prevalent in European and US older adults (\>60 years), Black and Asian minority ethnic population groups and in those with a high BMI. Secondly because 25(OH)D is known to have important immunoregulatory roles e.g. in downregulating pro-inflammatory cytokines TNF-α, IL-1, IL-2, IL-6, IL-8, IL-17, IFN-γ and upregulating anti-inflammatory TGFβ and IL-10. 25(OH)D also promotes Treg and effector CD8+ T cell differentiation and expansion. Furthermore, 25(OH)D has a role in preventing and reducing human respiratory infections e.g. influenza and in experimental animals is positively associated with virus specific CD8+ T cells. Vitamin D may also be an important modulator of hyperinflammatory response in patients with Covid-19 infection through cytokine storm suppression. As part of the Government's response to Covid-19, Public Health England has re-issued existing advice on vitamin D: https://www.nhs.uk/conditions/vitamins-and-minerals/vitamin-d/ This study will provide important information on vitamin D status as a possible risk factor in relation to COVID-19 infection in UK elderly and ethnic minority populations. Furthermore, the data generated could also have important implications for future supplementation and or vaccination strategies for COVID-19.