Defining the impact of pre-existing host immunity on SARS-CoV-2 incidence and COVID‑19 clinical outcome

Kaul, Rupert | $489,600

Ontario University of Toronto 2021 CIHR Project Grant

Clinical outcomes are highly variable after SARS-CoV-2 infection (COVID-19), ranging from asymptomatic infection to severe disease. Very soon after exposure to viruses our innate immune responses are triggered, while the development of adaptive host T cell responses takes longer but may give long-lasting protection against reinfection. Interestingly, T cell responses against COVID can be detected in about 50% of uninfected individuals, presumably induced by prior infection with other seasonal coronaviruses. We propose to study the impact of pre-infection innate immune responsiveness and coronavirus-specific T cell responses on subsequent COVID infection rates and disease severity. A June report from Kenya found that 10% of Nairobi residents had already had COVID-19, and we hypothesize that female sex workers are at particularly high risk due to their inability to maintain social distancing. Drs Beattie (London, UK), Kimani (Nairobi, Kenya) and Kaul (Toronto, Canada) established the Maisha Fiti cohort of female sex workers in Nairobi, Kenya in 2018, to study immune pathways linking violence experience to HIV risk: 750 HIV uninfected sex worker participants were enrolled in late 2019, just before the COVID pandemic struck, with the storage of blood plasma and viable peripheral blood mononuclear cells (PBMC) for subsequent immune analysis and collection of very detailed data regarding women’s experience of violence. All participants are now returning for repeat sampling and counselling; we have added a detailed survey regarding respiratory symptoms, and have received approval for SARS-CoV-19 serology. This will allow us to work with these unique pre-COVID blood samples to define the impact of pre-existing innate and COVID-specific immune parameters on subsequent SARS-CoV-2 acquisition and disease severity.

With funding from the Government of Canada

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