Multivariate analyses and machine learning link sex and age with antibody responses to SARS-CoV-2 and vaccination

Summary: Prevention of negative COVID-19 infection outcomes is associated with the quality of antibody responses, whose variance by age and sex is poorly understood. Network approaches identified sex and age effects in antibody responses and neutralization potential of de novo infection and vaccination throughout the COVID-19 pandemic. Neutralization values followed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific receptor binding immunoglobulin G (RIgG), spike immunoglobulin G (SIgG) and spike and receptor immunoglobulin G (S, and RIgA) levels based on COVID-19 status. Serum immunoglobulin A (IgA) antibody titers correlated with neutralization only in females 40–60 years old (y.o.). Network analysis found males could improve IgA responses after vaccination dose 2. Complex correlation analyses found vaccination induced less antibody isotype switching and neutralization in older persons, especially in females. Sex-dependent antibody and neutralization decayed the fastest in older males. Shown sex and age characterization can direct studies integrating cell-mediated responses to define yet elusive correlates of protection and inform age and sex precision-focused vaccine design.