Explaining the differential severity of COVID-19 between Indians in India and the UK

Emerging data suggest that Indian residents may be less susceptible to severe COVID-19 than Indians in the diaspora. It remains unclear whether these differences are real or due to data artefact. Hypothesized mechanisms for protection from COVID-19 include lower burden of obesity and cardio-metabolic disease, greater exposure to vitamin D, and cross-immunity from past infections and vaccinations. The aim of this study is to determine whether the risk of severe COVID-19 (defined as COVID-19 related hospitalisation or death) differs between Indian populations in India and the UK and the extent to which this is explained by differences in data quality, age structure, co-morbidities, and cross-immunity. This project will comprise two work packages: The first is an epidemiological study comparing the population prevalence of severe COVID-19 in India and the UK. Using anonymised longitudinal electronic health record data for 400,000 people of Indian ethnicity in the UK, we will quantify the prevalence of severe COVID-19 adjusted for age, sex, and co-morbidities. A parallel analysis will be conducted in India using COVID-19 surveillance and chronic disease registry data from 220,000 people in the extended cohorts of two established studies in the states of Karnataka and Telangana. The second work package will use detailed biomarker and phenotyping data available in a 10,000 person subset of the two Indian cohorts to conduct an in-depth mechanistic study to elucidate hypothesized relationships between COVID-19 severity, environmental (vitamin D levels) and socio-economic factors (cross-immunity from greater exposure to infections and lower rates of obesity and cardiometabolic co-morbidities due to undernutrition). Findings will be used to triangulate evidence on the differential severity of COVID-19 in global Indian populations and translated into recommendations for clinical and policy use targeted at reducing risk of severe COVID-19 in Indian populations worldwide.