Multivariate analyses and machine learning link sex and age with antibody responses to SARS-CoV-2 and vaccination
Miroslava Cuperlovic-Culf,
Steffany A.L. Bennett,
Yannick Galipeau,
Pauline S. McCluskie,
Corey Arnold,
Salman Bagheri,
Curtis L. Cooper,
Marc-André Langlois,
Jörg H. Fritz,
Ciriaco A. Piccirillo,
Angela M. Crawley
Affiliations
Miroslava Cuperlovic-Culf
Digital Technologies Research Centre, National Research Council of Canada, 1200 Montreal Road, Ottawa, ON K1A 0R6, Canada; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Steffany A.L. Bennett
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Yannick Galipeau
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Pauline S. McCluskie
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Corey Arnold
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Salman Bagheri
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Coronavirus Variants Rapid Response Network (CoVaRR-Net), Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada; Centre for Infection, Immunity, and Inflammation (CI3), University of Ottawa, Ottawa, ON, Canada
Curtis L. Cooper
Coronavirus Variants Rapid Response Network (CoVaRR-Net), Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada; Centre for Infection, Immunity, and Inflammation (CI3), University of Ottawa, Ottawa, ON, Canada; Clinical Epidemiology, Ottawa Hospital Research Institute, Ottawa, ON, Canada; Division of Infectious Diseases, Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, ON, Canada; Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
Marc-André Langlois
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Coronavirus Variants Rapid Response Network (CoVaRR-Net), Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
Jörg H. Fritz
Coronavirus Variants Rapid Response Network (CoVaRR-Net), Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada; Program in Infectious Diseases and Immunology in Global Health, The Research Institute of the McGill University Health Centre (RI-MUHC), Montréal, QC, Canada; Centre of Excellence in Translational Immunology (CETI), Montréal, QC, Canada; McGill University Research Centre on Complex Traits (MRCCT), Montréal, QC, Canada
Ciriaco A. Piccirillo
Coronavirus Variants Rapid Response Network (CoVaRR-Net), Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada; Program in Infectious Diseases and Immunology in Global Health, The Research Institute of the McGill University Health Centre (RI-MUHC), Montréal, QC, Canada; Centre of Excellence in Translational Immunology (CETI), Montréal, QC, Canada; McGill University Research Centre on Complex Traits (MRCCT), Montréal, QC, Canada
Angela M. Crawley
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Coronavirus Variants Rapid Response Network (CoVaRR-Net), Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada; Centre for Infection, Immunity, and Inflammation (CI3), University of Ottawa, Ottawa, ON, Canada; Corresponding author
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.
