The Humoral Immune Response to SARS-CoV-2 Vaccination and Infection

Abstract

Background: The coronavirus disease 2019 (COVID-19) pandemic resulted in over seven million deaths as of 2026 and an excess mortality of 18.2 million as of 2022. COVID-19 vaccines were instrumental in improving population immunity. However, initial phase 2/3 clinical trials excluded vulnerable clinical groups. Observational research was therefore needed to evaluate the long-term effectiveness of COVID-19 vaccines among high-risk clinical groups in a real-world context. The Stop the Spread Ottawa (SSO) cohort was utilized to accomplish this goal. Objectives: I. Describe the demographic and clinical characteristics of the SSO cohort; II. Identify predictors of COVID-19 vaccine humoral immunogenicity; III. Determine if immune compromised (IC) status, obesity, excessive alcohol consumption, or SSRI medication use influence the production and durability and/or neutralization activity of antibodies generated by COVID-19 vaccination; V. Determine if SSRIs impact the odds of developing post COVID-19 condition (PCC); VI. Explore the potential impact of imprinting on COVID-19 vaccine immunogenicity. Methods: Predictors of antibody titers after the second COVID-19 vaccine dose were identified by multivariable quantile regression. The impact of IC (after five doses), obesity (three doses), excessive alcohol consumption (four doses), and SSRI use (three doses) were assessed by multivariable multilevel robust linear regression with flexible modelling of time, segmented multilevel Bayesian robust linear regression, segmented multilevel linear regression, and multilevel robust linear regression with flexible modelling of time, respectively. Results: The SSO cohort was primarily White (89.0%), female (66.6%), and employed (83.2%) at baseline. A wide range of ages were represented. Older age and high-level IC (e.g., malignancy, organ/bone marrow transplant, systemic immunosuppressant, rheumatological disease, suppressed HIV) predicted impaired antibody production and neutralization activity following COVID-19 vaccination, whereas hybrid immunity and a wider interval between doses were associated with heightened humoral response. Antibody production and durability were impaired for high-level IC participants but not for obese participants, excessive alcohol consumers, or SSRI users. SSRI use was not associated with the odds of PCC. Conclusion: COVID-19 vaccination generated robust humoral response among obese individuals, excessive alcohol drinkers, and SSRI users. Humoral immunogenicity was impaired for high-level IC participants and older individuals; our findings support the prioritization of these populations in public health vaccination guidelines.