Determinants of Systemic SARS-CoV-2-Specific Antibody Responses to Infection and to Vaccination: A Secondary Analysis of Randomised Controlled Trial Data
Juana Claus,
Thijs ten Doesschate,
Esther Taks,
Priya A. Debisarun,
Gaby Smits,
Rob van Binnendijk,
Fiona van der Klis,
Lilly M. Verhagen,
Marien I. de Jonge,
Marc J. M. Bonten,
Mihai G. Netea,
Janneke H. H. M. van de Wijgert
Affiliations
Juana Claus
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, 3584 CG Utrecht, The Netherlands
Thijs ten Doesschate
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, 3584 CG Utrecht, The Netherlands
Esther Taks
Department of Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
Priya A. Debisarun
Department of Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
Gaby Smits
National Institute of Public Health and the Environment, 3720 BA Bilthoven, The Netherlands
Rob van Binnendijk
National Institute of Public Health and the Environment, 3720 BA Bilthoven, The Netherlands
Fiona van der Klis
National Institute of Public Health and the Environment, 3720 BA Bilthoven, The Netherlands
Lilly M. Verhagen
Department of Paediatric Infectious Diseases and Immunology, Amalia Children’s Hospital, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
Marien I. de Jonge
Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
Marc J. M. Bonten
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, 3584 CG Utrecht, The Netherlands
Mihai G. Netea
Department of Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
Janneke H. H. M. van de Wijgert
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, 3584 CG Utrecht, The Netherlands
SARS-CoV-2 infections elicit antibodies against the viral spike (S) and nucleocapsid (N) proteins; COVID-19 vaccines against the S-protein only. The BCG-Corona trial, initiated in March 2020 in SARS-CoV-2-naïve Dutch healthcare workers, captured several epidemic peaks and the introduction of COVID-19 vaccines during the one-year follow-up. We assessed determinants of systemic anti-S1 and anti-N immunoglobulin type G (IgG) responses using trial data. Participants were randomised to BCG or placebo vaccination, reported daily symptoms, SARS-CoV-2 test results, and COVID-19 vaccinations, and donated blood for SARS-CoV-2 serology at two time points. In the 970 participants, anti-S1 geometric mean antibody concentrations (GMCs) were much higher than anti-N GMCs. Anti-S1 GMCs significantly increased with increasing number of immune events (SARS-CoV-2 infection or COVID-19 vaccination): 104.7 international units (IU)/mL, 955.0 IU/mL, and 2290.9 IU/mL for one, two, and three immune events, respectively (p 10 concentrations were significantly associated with infection severity, and anti-S1 log10 concentration with COVID-19 vaccine type/dose. In univariable models, anti-N log10 concentration was also significantly associated with acute infection duration, and severity and duration of individual symptoms. Antibody concentrations were not associated with long COVID or long-term loss of smell/taste.