Incidence determinants and serological correlates of reactive symptoms following SARS-CoV-2 vaccination

Hayley Holt; David A Jolliffe; Mohammad Talaei; Sian Faustini; Giulia Vivaldi; Matthew Greenig; Alex G Richter; Ronan A Lyons; Christopher J Griffiths; Frank Kee; Aziz Sheikh; Gwyneth A Davies; Seif O Shaheen; Adrian R Martineau

doi:10.1038/s41541-023-00614-0

Incidence determinants and serological correlates of reactive symptoms following SARS-CoV-2 vaccination

NPJ Vaccines. 2023 Feb 25;8(1):26. doi: 10.1038/s41541-023-00614-0.

Authors

Hayley Holt^{1

2

3}, David A Jolliffe^{4

5}, Mohammad Talaei⁴, Sian Faustini⁶, Giulia Vivaldi^{4

7}, Matthew Greenig⁴, Alex G Richter⁶, Ronan A Lyons⁸, Christopher J Griffiths^{4

5}, Frank Kee⁹, Aziz Sheikh¹⁰, Gwyneth A Davies⁸, Seif O Shaheen⁴, Adrian R Martineau^{4

7

5}

Affiliations

¹ Wolfson Institute of Population Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. h.holt@qmul.ac.uk.
² Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. h.holt@qmul.ac.uk.
³ Asthma UK Centre for Applied Research, Queen Mary University of London, London, UK. h.holt@qmul.ac.uk.
⁴ Wolfson Institute of Population Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
⁵ Asthma UK Centre for Applied Research, Queen Mary University of London, London, UK.
⁶ Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
⁷ Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
⁸ Population Data Science, Swansea University Medical School, Singleton Park, Swansea, UK.
⁹ Centre for Public Health Research (NI), Queen's University Belfast, Belfast, UK.
¹⁰ Usher Institute, University of Edinburgh, Edinburgh, UK.

Abstract

Prospective population-based studies investigating associations between reactive symptoms following SARS-CoV-2 vaccination and serologic responses to vaccination are lacking. We therefore conducted a study in 9003 adults from the UK general population receiving SARS-CoV-2 vaccines as part of the national vaccination programme. Titres of combined IgG/IgA/IgM responses to SARS-CoV-2 spike (S) glycoprotein were determined in eluates of dried blood spots collected from all participants before and after vaccination. 4262 (47.3%) participants experienced systemic reactive symptoms after a first vaccine dose. Factors associating with lower risk of such symptoms included older age (aOR per additional 10 years of age 0.85, 95% CI: 0.81-0.90), male vs. female sex (0.59, 0.53-0.65) and receipt of an mRNA vaccine vs. ChAdOx1 nCoV-19 (0.29, 0.26-0.32 for BNT162b2; 0.06, 0.01-0.26 for mRNA-1273). Higher risk of such symptoms was associated with SARS-CoV-2 seropositivity and COVID-19 symptoms prior to vaccination (2.23, 1.78-2.81), but not with SARS-CoV-2 seropositivity in the absence of COVID-19 symptoms (0.94, 0.81-1.09). Presence vs. absence of self-reported anxiety or depression at enrolment associated with higher risk of such symptoms (1.24, 1.12-1.39). Post-vaccination anti-S titres were higher among participants who experienced reactive symptoms after vaccination vs. those who did not (P < 0.001). We conclude that factors influencing risk of systemic symptoms after SARS-CoV-2 vaccination include demographic characteristics, pre-vaccination SARS-CoV-2 serostatus and vaccine type. Participants experiencing reactive symptoms following SARS-CoV-2 vaccination had higher post-vaccination titres of IgG/A/M anti-S antibodies. Improved public understanding of the frequency of reactogenic symptoms and their positive association with vaccine immunogenicity could potentially increase vaccine uptake.