CARDINNATE: Variation in innate immune activation and cardiovascular disease risk as drivers of COVID19 outcome in South Asians in UK and India

In the UK, individuals of South Asian heritage have a higher COVID-19 mortality rate than other ethnic groups, even after adjusting for age and social., , factors. This is driven by a greater risk of in-hospital death rather than an increased rate of admissions, in part related to a higher prevalence of cardiovascular disease (CVD) and diabetes which are recognised risk factors for severe COVID-19. By contrast, mortality rates for COVID-19 in India are markedly lower than the UK. Severe COVID-19 is associated with profound systemic immune dysregulation, haemodynamic and thrombotic complications. Multiple lines of evidence suggest that innate immune mechanisms, specifically variation in the regulation of the type 1 interferon (IFN) response and the subsequent dysregulation of cellular innate and adaptive immunity, may be very important determining factors in COVID-19 pathogenesis. Hence these mechanisms are good candidates for underlying increased mortality risk in UK South Asians and set a platform for understanding why the situation is different in India. Our multi-disciplinary UK and India team will elucidate the inter-relationship among innate immune mechanisms, pre-existing CVD/diabetes and environment (India versus UK). Differences in innate immunity, which provides a first line of defence to infection, are captured by the term "trained immunity", reflecting its conditioning in part via IFN, by exposure to endemic environmental pathogens, diet, and inflammatory conditions including CVD/diabetes. Hence, evident differences in these factors for South Asians in India versus the UK may profoundly affect the speed and strength of first-phase immune responses to SARS CoV2, as well as attendant cardiovascular damage and dysfunction, to collectively drive systemic immunopathology and the differences in COVID-19 mortality between the UK and India.