Systemic Adverse Effects Induced by the BNT162b2 Vaccine Are Associated with Higher Antibody Titers from 3 to 6 Months after Vaccination

  1. Ryousuke Koike
  2. Michiru Sawahata
  3. Yosikazu Nakamura
  4. Yushi Nomura
  5. Otohiro Katsube
  6. Koichi Hagiwara
  7. Seiji Niho
  8. Norihiro Masuda
  9. Takaaki Tanaka
  10. Kumiya Sugiyama

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Abstract

Objective: We aimed to determine the relationship between vaccine-related adverse effects and antibody (Ab) titers from 3 to 6 months after the second dose of the BNT162b2 coronavirus disease 2019 (COVID-19) mRNA vaccine (Pfizer/BioNTech) in Japan. Methods: We enrolled 378 healthcare workers (255 women and 123 men) whose Ab titers were analyzed 3 and 6 months after the second dose in our previous study and whose characteristics and adverse effects were collected previously by using a structured self-report questionnaire. Results: The workers’ median age was 44 years. Although injection-site symptoms occurred with almost equal frequency between the first and second doses, systemic adverse effects, such as general fatigue and fever, were significantly more frequent after the second dose than after the first dose. Multivariate analysis showed that fever was significantly correlated with female participants for the second dose (odds ratio (OR), 2.139; 95% confidence interval (95% CI), 1.185–3.859), older age for the first dose (OR, 0.962; 95% CI, 0.931–0.994) and second dose (OR, 0.957; 95% CI, 0.936–0.979), and dyslipidemia for the first dose (OR, 8.750; 95% CI, 1.814–42.20). Age-adjusted Ab titers at 3 months after vaccination were 23.7% and 23.4% higher in patients with a fever than in those without a fever after the first and second dose, respectively. In addition, age-adjusted Ab titers at 3 and 6 months after the second dose were, respectively, 21.7% and 19.3% higher in the group in which an anti-inflammatory agent was used than in the group without the use of an anti-inflammatory agent. Conclusion: Participants with systemic adverse effects tend to have higher Ab titers from 3 to 6 months after the second dose of the BNT162b2 vaccine. Our results may encourage vaccination, even among people with vaccine hesitancy related to relatively common systemic adverse effects.

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  1. Version published to 10.3390/vaccines10030451
  2. ScreenIT

    SciScore for 10.1101/2022.01.23.22269706: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: The Ethics Committee of National Hospital Organization Utsunomiya National Hospital (No. 03-01; April 19
    Consent: 9, 2021) approved this study, and written informed consent was obtained from all participants before their enrollment.
    Sex as a biological variable(255 women, 123 men) at the National Hospital Organization Utsunomiya National Hospital in Tochigi Prefecture, Japan and analyzed their Ab titers at 3 and 6 months after the second of two BNT162b2 vaccine inoculations administered 3 weeks apart in February and March 2021.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    To calculate Spearman’s rank correlation coefficient and perform the Mann–Whitney U test, chi-square test, and multivariate logistic regression analysis, we used the Statistical Package for Social Sciences (SPSS) version 28 (IBM Japan, Ltd., Tokyo, Japan).
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Some limitations and possible sources of bias in this study include the following. First, the participants were limited in number and were all healthcare workers vaccinated at a single national hospital in Tochigi Prefecture. Therefore, the results obtained in this study might not be widely generalizable or even generalizable within Japan. Second, we may need additional analysis and discussion to determine whether age is an important factor independently associated with adverse effects. One possibility is that fever may be an independent factor associated with higher Ab titers, but not age. In this case, because most of the participants with fever were younger, younger age may not be independently associated with a higher Ab titer. The opposite is also a possibility. In addition, both fever and age may be important factors. Therefore, we cannot determine whether fever or young age is a more important factor. In conclusion, participants with systemic adverse effects had about 20% higher Ab titers at 3 and 6 months after the second dose of the BNT162b2 vaccine. Although the systemic adverse effects induced by the BNT162b2 vaccine are sometimes unpleasant, higher Ab titers should reduce the risk of a more severe COVID-19 infection. We hope that our results will encourage vaccine uptake.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

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  3. Version published to 10.1101/2022.01.23.22269706v1 on medRxiv