Characterizing the SARS-CoV-2 antibody response and associations with patient factors: Serological profiling of participants enrolled in the GENCOV study

INTRODUCTION: The GENCOV study sought to evaluate serological differences between individuals with differing COVID-19 severity and outcomes. We assessed the SARS-CoV-2 antibody response of GENCOV participants cross-sectionally 1-, 6-, and 12-months following COVID-19 diagnosis to identify patient factors associated with more robust and durable humoral immune responses. MATERIALS AND METHODS: COVID-19 patients and a control cohort of vaccinated infection-naïve participants were recruited at hospital sites across the Greater Toronto Area in Ontario, Canada. Commercially available and laboratory-developed serological assays were used to characterize features of participants' antibody responses, including both binding and neutralizing antibodies. Regression analyses were performed to identify associations between participant characteristics and features of the SARS-CoV-2 antibody response. RESULTS: Samples were obtained from participants 1- (n = 938), 6- (n = 842), and 12-months (n = 662) post-infection or vaccination. At all time points, vaccinees, and to a greater extent those who were both infected and vaccinated, had significantly elevated anti-spike antibody levels compared to unvaccinated participants. Increasing age and/or illness severity were associated with significantly higher antibody levels among unvaccinated participants. Among vaccines, those who were vaccinated after infection (i.e., hybrid immunity) had consistently higher antibody levels compared to participants who were infection-naïve or vaccinated before their infection (i.e., breakthrough infections). Additionally, receiving more vaccine doses and having a more recent vaccination were strongly associated with higher antibody levels across all time points. CONCLUSIONS: Our findings highlight various patient factors, including vaccination, which contribute to robust, durable SARS-CoV-2 antibody responses. Overall, the findings presented here may inform future vaccine development and rollout plans.