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- Minke R Holwerda1, Christina E Hoeve1, Anne J Huiberts1, Gerco den Hartog1, Hester E de Melker1, Susan van den Hof1, Mirjam J Knol1
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1Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands
Correspondence:
Mirjam J Knol
mirjam.knolrivm.nl
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Citation style for this article:Holwerda Minke R, Hoeve Christina E, Huiberts Anne J, den Hartog Gerco, de Melker Hester E, van den Hof Susan, Knol Mirjam J.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.Euro Surveill. 2024;29(25):pii=2300585.https://doi.org/10.2807/1560-7917.ES.2024.29.25.2300585Received: 24 Oct 2023;Accepted: 11 Mar 2024
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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.
©
This work is licensed under a Creative Commons Attribution 4.0 International License.
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References
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.
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)00085-4PMID: 33453149
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.CD015477PMID: 36473651
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/s12916-021-02059-5PMID: 34315454
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.2022.01.013PMID: 35067381
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.
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/s41541-019-0132-6PMID: 31583123
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.abj9256PMID: 34158390
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/s40520-021-01987-9PMID: 34652783
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.2021.210PMID: 34038996
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.2022.37908PMID: 36269359
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.2022.01.002PMID: 35033389
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/vaccines9101089PMID: 34696197
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/vaccines9101063PMID: 34696171
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.2022.876533PMID: 35711413
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
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
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
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
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
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.2021.40364PMID: 34935921
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/10.2196/29872PMID: 34709184
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/vaccines10122017PMID: 36560426
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.
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.
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
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.2022.07.002PMID: 35843565
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/s41591-022-01721-6PMID: 35165453
Orlandi C, Stefanetti G, Barocci S, Buffi G, Diotallevi A, Rocchi E, et al. Comparing heterologous and hom*ologous COVID-19 vaccination: a longitudinal study of antibody decay. Viruses. 2023;15(5):1162. https://doi.org/10.3390/v15051162PMID: 37243247
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/s41562-021-01122-8PMID: 33972767
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/vaccines10030439PMID: 35335071
Cheng A, Hsieh MJ, Chang SY, Ieong SM, Cheng CY, Sheng WH, et al. Correlation of adverse effects and antibody responses following hom*ologous and heterologous COVID19 prime-boost vaccinations. J Formos Med Assoc. 2023;122(5):384-92. https://doi.org/10.1016/j.jfma.2022.12.002PMID: 36564299
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.2023.01.050PMID: 36737319
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/ciab172PMID: 33624751
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/NEJMc2202542PMID: 35297591
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)00271-7PMID: 35550261
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/s41591-022-02031-7PMID: 36202997
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.0269917PMID: 35687563
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/ciac852PMID: 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; <span class="generated">Accepted</span>: 11 Mar 2024 </span></p>
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