Association of Self-Reported Systemic Reactions Following SARS-CoV-2 Vaccination With Immunological Response in The Danish National Cohort Study of Effectiveness and Safety of SARS-CoV-2 Vaccines (ENFORCE)

Wendy P Bannister, Dorthe Raben, Palle Valentiner-Branth, Martin Tolstrup, Lykke Larsen, Britta Tarp, Mette Brouw Iversen, Ole Schmeltz Søgaard, Sisse Rye Ostrowski, Nina Breinholt Stærke, Marie Louise Jakobsen, Susan Olaf Lindvig, Maria Ruwald Juhl, Isik Somuncu Johansen, Ahmed B Mustafa, Lars Østergaard, Fredrikke Dam Larsen, Lene Surland Knudsen, Vibeke Klastrup, Lothar WieseThomas Benfield, Kristine Toft Petersen, Kasper K Iversen, Henrik Nielsen, Joanne Reekie*, Jens Lundgren, the ENFORCE Study Group

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

BACKGROUND: Side effects to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are a key concern contributing to vaccine hesitancy, but more individuals may be encouraged if SARS-CoV-2 vaccines were known to lead to a stronger immune response.

METHODS: Included were adult participants from the Danish National Cohort Study of Effectiveness and Safety of SARS-CoV-2 Vaccines (ENFORCE) who completed a questionnaire to assess systemic reactions following SARS-CoV-2 vaccination (BTN162b2, mRNA-1273, ChAdOx1) and had SARS-CoV-2 spike immunoglobulin G (IgG) levels measured at baseline and post-vaccine. A symptom score was developed to measure severity of systemic adverse reactions (+1 for each moderate, +2 for each severe). Post-vaccination SARS-CoV-2 spike IgG levels were compared between participants with different scores using multivariable linear regression.

RESULTS: A total of 6528 participants were included (56.3% females; median age [interquartile range], 64 [54-75] years). After the first vaccination, no association was found between symptom score and post-vaccine dose spike IgG level ( P = .575). Following the second vaccination, significantly higher spike IgG levels were observed according to higher symptom scores ( P < .001); adjusted geometric mean ratios were 1.16 (95% CI, 1.04-1.30), 1.24 (95% CI, 1.09-1.41), 1.25 (95% CI, 1.06-1.46), and 1.21 (95% CI, 1.08-1.35), for scores of 2, 3, 4, and ≥5, respectively, compared with a score of 0. After adjustment for pre-vaccine dose spike IgG, this association was attenuated.

CONCLUSIONS: An association was found between more severe adverse reactions and stronger antibody response after the second vaccination but not the first, likely attributed to higher levels of preexisting immunity gained from response to first vaccination. Regardless of side effects, most people experienced an effective immune response following vaccination.

Original languageEnglish
Article numberofad248
JournalOpen Forum Infectious Diseases
Volume10
Issue number6
Number of pages19
ISSN2328-8957
DOIs
Publication statusPublished - Jun 2023

Keywords

  • COVID-19 vaccines
  • SARS-CoV-2
  • adverse drug reactions
  • antibody response

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