SARS-CoV-2 memory response in non-hospitalised cases: immunology in the context of a population-based cohort study

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Background The study of non-hospitalised COVID-19 cases provides a context for improved understanding of the immune response to existing and new infections. Population-based cohorts provide a unique opportunity to do this in relation to rich longitudinal pre- and pan-pandemic data. The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1990-1992 and has subsequently followed participants for over 30 years. Methods A study comprising three clinic visits was implemented, in response to the COVID-19 pandemic, amongst ALSPAC participants to measure SARS-CoV-2 specific humoral and cellular responses longitudinally. Here we present data from the first clinic in December 2020 before the start of the UK vaccination campaign and examine associations with a set of exemplar pre- and pan-pandemic health factors. Results We observed humoral and cellular memory immune responses to SARS-CoV-2 infection in mild cases of COVID-19 up to 9 months post-infection. Symptomatic infection elicited a memory immune response of greater magnitude, though there was variation in response in both asymptomatic and symptomatic individuals. We examined health factors associated with severe COVID-19 and found that cardio-metabolomic, respiratory and immune-related health factors associate with a memory immune response of higher magnitude. For example, in older participants (mean age 58 years), higher BMI was associated with an immune memory response of greater magnitude, particularly with anti-S and anti-N binding antibodies. Conclusions We set out to illustrate the use of cohort studies to deliver detailed immunological data and to provide example analyses of how life course health factors can be examined in relation to the immune response following a widespread and novel infection. We expanded this assessment to include longitudinally assessed traits, opening up the potential for the more common use of longitudinal population studies for the better understanding the aetiology of infection outcome.