Grant: Op. Gr.:Emerging COVID-19 Res. Gaps & Priorities (July 2021) - Immune Responses

Background: Canada is seeing a COVID-19 resurgence as SARS-CoV-2 variants continue to emerge globally and herd immunity remains elusive. It is unclear whether there will be a decline in immune protection over time, or with the emergence of viral variants. Methods: From December 2020 to June 2021, invitations went out to select Ontario Health Study participants requesting that they complete an online questionnaire and submit dried blood spot samples. The questionnaire includes details around vaccination, previous COVID-19 infection, and underlying medical conditions and medications taken. The study included 10,569 participants (age 21 to 93), with 62% women. Collection of second dried blood spot samples is underway. Dried blood spot samples will be tested for antibodies to SARS-CoV-2 (anti-spike IgG, anti-receptor binding domain of spike (RBD) IgG, and anti-nucleocapsid (N) IgG) and will undergo DNA extraction and genotyping. Data will be linked to COVID-19 lab results and hospitalization data, including ICU admission and death. Objectives: Measured levels of vaccine-induced immune markers (antibody levels) will be related to vaccine effectiveness by comparing incidence of SARS-CoV-2 infection, hospitalization, and mortality in a population of vaccinated and unvaccinated participants. We will also assess variation in immune response to vaccination by viral variant, vaccine factors (such as type, product, number of doses, interval between doses, time since vaccination) and intrinsic host factors (such as age, sex, genetics, and comorbidities). Implications: Identifying immune correlates of protection will be important because they can be used as surrogate endpoints in assessing vaccine efficacy, and the durability of protection over time will provide insights into the necessity for booster vaccination. Also, identification of host and vaccine factors that affect immunity will allow for tailored recommendations regarding vaccine distribution.