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Abstract

Background

Non-severe adverse events (AE) including pain at injection site or fever are common after COVID-19 vaccination.

Aim

To describe determinants of AE after COVID-19 vaccination and investigate the association between AE and pre- and post-vaccination antibody concentrations.

Methods

Participants of an ongoing prospective cohort study (VASCO) completed a questionnaire on AE within 2 months after vaccination and provided 6 monthly serum samples during May 2021–November 2022. Logistic regression analyses were performed to investigate AE determinants after mRNA vaccination, including pre-vaccination Ig antibody concentrations against the SARS-CoV-2 spike protein receptor binding domain. Multivariable linear regression was performed in SARS-CoV-2-naive participants to assess the association between AE and log-transformed antibody concentrations 3–8 weeks after mRNA vaccination.

Results

We received 47,947 completed AE questionnaires by 28,032 participants. In 42% and 34% of questionnaires, injection site and systemic AE were reported, respectively. In 2.2% of questionnaires, participants sought medical attention. AE were reported more frequently by women, younger participants (< 60 years), participants with medical risk conditions and Spikevax recipients (vs Comirnaty). Higher pre-vaccination antibody concentrations were associated with higher incidence of systemic AE after the second and third dose, but not with injection site AE or AE for which medical attention was sought. Any AE after the third dose was associated with higher post-vaccination antibody concentrations (geometric mean concentration ratio: 1.38; 95% CI: 1.23–1.54).

Conclusions

Our study suggests that high pre-vaccination antibody levels are associated with AE, and experiencing AE may be a marker for higher antibody response to vaccination.

© Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
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2024-06-20
2024-06-30
http://instance.metastore.ingenta.com/content/10.2807/1560-7917.ES.2024.29.25.2300585
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References

  1. World Health Organization (WHO). Coronavirus disease (COVID-19) pandemic 2023.Geneva: WHO. [Accessed: 19 Nov 2023]. Available from: https://www.who.int/europe/emergencies/situations/covid-19.
  2. Cavaleri M, Enzmann H, Straus S, Cooke E. The European Medicines Agency’s EU conditional marketing authorisations for COVID-19 vaccines. Lancet. 2021;397(10272):355-7.  https://doi.org/10.1016/S0140-6736(21)00085-4  PMID: 33453149 
  3. Graña C, Ghosn L, Evrenoglou T, Jarde A, Minozzi S, Bergman H, et al. Efficacy and safety of COVID-19 vaccines. Cochrane Database Syst Rev. 2022;12(12):CD015477.  https://doi.org/10.1002/14651858.CD015477  PMID: 36473651 
  4. Wu Q, Dudley MZ, Chen X, Bai X, Dong K, Zhuang T, et al. Evaluation of the safety profile of COVID-19 vaccines: a rapid review. BMC Med. 2021;19(1):173.  https://doi.org/10.1186/s12916-021-02059-5  PMID: 34315454 
  5. Rolfes L, Härmark L, Kant A, van Balveren L, Hilgersom W, van Hunsel F. COVID-19 vaccine reactogenicity - A cohort event monitoring study in the Netherlands using patient reported outcomes. Vaccine. 2022;40(7):970-6.  https://doi.org/10.1016/j.vaccine.2022.01.013  PMID: 35067381 
  6. European Medicines Agency (EMA). Guideline on good pharmacovigilance practices (GVP) Annex 1 - Definitions (Rev 4) - EMA/876333/2011 Rev 4. London: EMA; 2017. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-good-pharmacovigilance-practices-annex-i-definitions-rev-4_en.pdf.
  7. Hervé C, Laupèze B, Del Giudice G, Didierlaurent AM, Tavares Da Silva F. The how’s and what’s of vaccine reactogenicity. NPJ Vaccines. 2019;4(1):39.  https://doi.org/10.1038/s41541-019-0132-6  PMID: 31583123 
  8. Sprent J, King C. COVID-19 vaccine side effects: The positives about feeling bad. Sci Immunol. 2021;6(60):eabj9256.  https://doi.org/10.1126/sciimmunol.abj9256  PMID: 34158390 
  9. Oyebanji OA, Wilson B, Keresztesy D, Carias L, Wilk D, Payne M, et al. Does a lack of vaccine side effects correlate with reduced BNT162b2 mRNA vaccine response among healthcare workers and nursing home residents? Aging Clin Exp Res. 2021;33(11):3151-60.  https://doi.org/10.1007/s40520-021-01987-9  PMID: 34652783 
  10. Hwang YH, Song KH, Choi Y, Go S, Choi SJ, Jung J, et al. Can reactogenicity predict immunogenicity after COVID-19 vaccination? Korean J Intern Med (Korean Assoc Intern Med). 2021;36(6):1486-91.  https://doi.org/10.3904/kjim.2021.210  PMID: 34038996 
  11. Hermann EA, Lee B, Balte PP, Xanthakis V, Kirkpatrick BD, Cushman M, et al. Association of symptoms after COVID-19 vaccination with anti-SARS-CoV-2 antibody response in the Framingham Heart Study. JAMA Netw Open. 2022;5(10):e2237908.  https://doi.org/10.1001/jamanetworkopen.2022.37908  PMID: 36269359 
  12. Uwamino Y, Kurafuji T, Sato Y, Tomita Y, Shibata A, Tanabe A, et al. Young age, female sex, and presence of systemic adverse reactions are associated with high post-vaccination antibody titer after two doses of BNT162b2 mRNA SARS-CoV-2 vaccination: An observational study of 646 Japanese healthcare workers and university staff. Vaccine. 2022;40(7):1019-25.  https://doi.org/10.1016/j.vaccine.2022.01.002  PMID: 35033389 
  13. Bauernfeind S, Salzberger B, Hitzenbichler F, Scigala K, Einhauser S, Wagner R, et al. Association between reactogenicity and immunogenicity after vaccination with BNT162b2. Vaccines (Basel). 2021;9(10):1089.  https://doi.org/10.3390/vaccines9101089  PMID: 34696197 
  14. Held J, Esse J, Tascilar K, Steininger P, Schober K, Irrgang P, et al. Reactogenicity correlates only weakly with humoral immunogenicity after COVID-19 vaccination with BNT162b2 mRNA (Comirnaty). Vaccines (Basel). 2021;9(10):1063.  https://doi.org/10.3390/vaccines9101063  PMID: 34696171 
  15. Ogrič M, Žigon P, Podovšovnik E, Lakota K, Sodin-Semrl S, Rotar Ž, et al. Differences in SARS-CoV-2-Specific antibody responses after the first, second, and third doses of BNT162b2 in naïve and previously infected individuals: a 1-year observational study in healthcare professionals. Front Immunol. 2022;13:876533.  https://doi.org/10.3389/fimmu.2022.876533  PMID: 35711413 
  16. Huiberts AJ, Kooijman MN, Melker HEd, Hahne SJ, Grobbee DE, Hoeve C, et al. Design and baseline description of an observational population-based cohort study on COVID-19 vaccine effectiveness in the Netherlands - The VAccine Study COvid-19 (VASCO). Research Square. Preprint. 2022 .  https://doi.org/10.21203/rs.3.rs-1645696/v1 
  17. Pluijmaekers A, Melker Hd. The National Immunisation Programme in the Netherlands. Surveillance and developments in 2021-2022. Bilthoven: National Institute for Public Health and the Environment; 2022. Available from: https://www.rivm.nl/bibliotheek/rapporten/2022-0042.pdf
  18. Højsgaard S, Halekoh U, Yan J. The R Package geepack for Generalized Estimating Equations. J Stat Softw. 2006;15(2):1-11.  https://doi.org/10.18637/jss.v015.i02 
  19. R Core Team. R: A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2018. Available from: https://www.R-project.org
  20. Wickham HAM, Bryan J, Chang WML, François R, Grolemund GHA, Henry L, et al. Welcome to the tidyverse. J Open Source Softw. 2019;4(43):1686.  https://doi.org/10.21105/joss.01686 
  21. Beatty AL, Peyser ND, Butcher XE, Cocohoba JM, Lin F, Olgin JE, et al. Analysis of COVID-19 vaccine type and adverse effects following vaccination. JAMA Netw Open. 2021;4(12):e2140364.  https://doi.org/10.1001/jamanetworkopen.2021.40364  PMID: 34935921 
  22. Tsai R, Hervey J, Hoffman K, Wood J, Johnson J, Deighton D, et al. COVID-19 vaccine hesitancy and acceptance among individuals with cancer, autoimmune diseases, or other serious comorbid conditions: cross-sectional, internet-based survey. JMIR Public Health Surveill. 2022;8(1):e29872.  https://doi.org/10.2196/29872  PMID: 34709184 
  23. Salter SM, Li D, Trentino K, Nissen L, Lee K, Orlemann K, et al. Safety of four COVID-19 vaccines across primary doses 1, 2, 3 and booster: a prospective cohort study of Australian community pharmacy vaccinations. Vaccines (Basel). 2022;10(12):2017.  https://doi.org/10.3390/vaccines10122017  PMID: 36560426 
  24. European Medicines Agency (EMA). Comirnaty: EPAR- product information. Amsterdam: EMA; 2022. Available from: https://www.ema.europa.eu/en/documents/product-information/comirnaty-epar-product-information_en.pdf.
  25. European Medicines Agency (EMA). Spikevax (previously COVID-19 Vaccine Moderna): EPAR - product information. Amsterdam: EMA; 2022. Available from: https://www.ema.europa.eu/en/documents/product-information/spikevax-previously-covid-19-vaccine-moderna-epar-product-information_en.pdf.
  26. European Medicines Agency (EMA). AstraZeneca’s COVID-19 vaccine: EMA finds possible link to very rare cases of unusual blood clots with low blood platelets 2021. Amsterdam: EMA. [Accessed: 27 Feb 2024]. Available from: https://www.ema.europa.eu/en/news/astrazenecas-covid-19-vaccine-ema-finds-possible-link-very-rare-cases-unusual-blood-clots-low-blood-platelets
  27. Braun E, Horowitz NA, Leiba R, Weissman A, Mekel M, Shachor-Meyouhas Y, et al. Association between IgG antibody levels and adverse events after first and second Bnt162b2 mRNA vaccine doses. Clin Microbiol Infect. 2022;28(12):1644-8.  https://doi.org/10.1016/j.cmi.2022.07.002  PMID: 35843565 
  28. Wei J, Pouwels KB, Stoesser N, Matthews PC, Diamond I, Studley R, et al. Antibody responses and correlates of protection in the general population after two doses of the ChAdOx1 or BNT162b2 vaccines. Nat Med. 2022;28(5):1072-82.  https://doi.org/10.1038/s41591-022-01721-6  PMID: 35165453 
  29. Orlandi C, Stefanetti G, Barocci S, Buffi G, Diotallevi A, Rocchi E, et al. Comparing heterologous and homologous COVID-19 vaccination: a longitudinal study of antibody decay. Viruses. 2023;15(5):1162.  https://doi.org/10.3390/v15051162  PMID: 37243247 
  30. Mathieu E, Ritchie H, Ortiz-Ospina E, Roser M, Hasell J, Appel C, et al. A global database of COVID-19 vaccinations. Nat Hum Behav. 2021;5(7):947-53.  https://doi.org/10.1038/s41562-021-01122-8  PMID: 33972767 
  31. Azzolini E, Canziani LM, Voza A, Desai A, Pepys J, De Santis M, et al. Short-term adverse events and antibody response to the BNT162b2 SARS-CoV-2 vaccine in 4156 health care professionals. Vaccines (Basel). 2022;10(3):439.  https://doi.org/10.3390/vaccines10030439  PMID: 35335071 
  32. Cheng A, Hsieh MJ, Chang SY, Ieong SM, Cheng CY, Sheng WH, et al. Correlation of adverse effects and antibody responses following homologous and heterologous COVID19 prime-boost vaccinations. J Formos Med Assoc. 2023;122(5):384-92.  https://doi.org/10.1016/j.jfma.2022.12.002  PMID: 36564299 
  33. Hamada H, Futamura M, Ito H, Yamamoto R, Yata K, Iwatani Y, et al. Association of a third vaccination with antibody levels and side reactions in essential workers: A prospective cohort study. Vaccine. 2023;41(9):1632-7.  https://doi.org/10.1016/j.vaccine.2023.01.050  PMID: 36737319 
  34. den Hartog G, Vos ERA, van den Hoogen LL, van Boven M, Schepp RM, Smits G, et al. Persistence of antibodies to severe acute respiratory syndrome coronavirus 2 in relation to symptoms in a nationwide prospective study. Clin Infect Dis. 2021;73(12):2155-62.  https://doi.org/10.1093/cid/ciab172  PMID: 33624751 
  35. Regev-Yochay G, Gonen T, Gilboa M, Mandelboim M, Indenbaum V, Amit S, et al. Efficacy of a fourth dose of Covid-19 mRNA vaccine against Omicron. N Engl J Med. 2022;386(14):1377-80.  https://doi.org/10.1056/NEJMc2202542  PMID: 35297591 
  36. Munro APS, Feng S, Janani L, Cornelius V, Aley PK, Babbage G, et al. Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial. Lancet Infect Dis. 2022;22(8):1131-41.  https://doi.org/10.1016/S1473-3099(22)00271-7  PMID: 35550261 
  37. Chalkias S, Eder F, Essink B, Khetan S, Nestorova B, Feng J, et al. Safety, immunogenicity and antibody persistence of a bivalent Beta-containing booster vaccine against COVID-19: a phase 2/3 trial. Nat Med. 2022;28(11):2388-97.  https://doi.org/10.1038/s41591-022-02031-7  PMID: 36202997 
  38. Kobashi Y, Shimazu Y, Kawamura T, Nishikawa Y, Omata F, Kaneko Y, et al. Factors associated with anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein antibody titer and neutralizing activity among healthcare workers following vaccination with the BNT162b2 vaccine. PLoS One. 2022;17(6):e0269917.  https://doi.org/10.1371/journal.pone.0269917  PMID: 35687563 
  39. Bettinger JA, Irvine MA, Shulha HP, Valiquette L, Muller MP, Vanderkooi OG, et al. Adverse events following immunization with mRNA and viral vector vaccines in individuals with previous SARS-CoV-2 infection from the Canadian National Vaccine Safety Network. Clin Infect Dis. 2022;76(6):1088-102.  https://doi.org/10.1093/cid/ciac852  PMID: 36310514 
Association between adverse events after COVID-19 vaccination and anti-SARS-CoV-2 antibody concentrations, the Netherlands, May 2021 to November 2022: a population-based prospective cohort study
<p class="citation"> <span>Citation style for this article:</span> <span class="meta-value authors"> <a href="/search?value1=Minke+R+Holwerda&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Holwerda Minke R</a>, <a href="/search?value1=Christina+E+Hoeve&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Hoeve Christina E</a>, <a href="/search?value1=Anne+J+Huiberts&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Huiberts Anne J</a>, <a href="/search?value1=Gerco+den+Hartog&option1=author&noRedirect=true" class="nonDisambigAuthorLink">den Hartog Gerco</a>, <a href="/search?value1=Hester+E+de+Melker&option1=author&noRedirect=true" class="nonDisambigAuthorLink">de Melker Hester E</a>, <a href="/search?value1=Susan+van+den+Hof&option1=author&noRedirect=true" class="nonDisambigAuthorLink">van den Hof Susan</a>, <a href="/search?value1=Mirjam+J+Knol&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Knol Mirjam J</a></span>. Association between adverse events after COVID-19 vaccination and anti-SARS-CoV-2 antibody concentrations, the Netherlands, May 2021 to November 2022: a population-based prospective cohort study. <a href="/content/ecdc">Euro Surveill.</a> 2024;29(25):pii=2300585. <a href="https://doi.org/10.2807/1560-7917.ES.2024.29.25.2300585" title="doi link" target="_blank">https://doi.org/10.2807/1560-7917.ES.2024.29.25.2300585</a> <span class="ES_Article_citation"> <span class="generated">Received</span>: 24 Oct 2023;&nbsp;&nbsp; <span class="generated">Accepted</span>: 11 Mar 2024 </span> </p>
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