{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T02:35:32Z","timestamp":1767839732549,"version":"3.49.0"},"reference-count":29,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,13]],"date-time":"2022-03-13T00:00:00Z","timestamp":1647129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Short-term adverse events are common following the BNT162b2 vaccine for SARS-Cov-2 and have been possibly associated with IgG response. We aimed to determine the incidence of adverse reactions to the vaccine and the impact on IgG response. Our study included 4156 health-care professionals who received two doses of the BNT162b2 vaccine 21 days apart and obtained 6113 online questionnaires inquiring about adverse events. The serum response was tested in 2765 subjects 10 days after the second dose. Adverse events, most frequently a local reaction at the site of injection, were reported by 39% of subjects. Multivariate analysis showed that female sex (odds ratio\u2014OR\u20141.95; 95% confidence interval\u2014CI\u20141.74\u20132.19; p &lt; 0.001), younger age (OR 0.98 per year, p &lt; 0.001), second dose of vaccine (OR 1.36, p &lt; 0.001), and previous COVID-19 infection (OR 1.41, p &lt; 0.001) were independently associated with adverse events. IgG response was significantly higher in subjects with adverse events (1110 AU\/mL\u2014IQR 345-1630 vs. 386 AU\/mL, IQR 261-1350, p &lt; 0.0001), and the association was more pronounced in subjects experiencing myalgia, fever, and lymphadenopathy. We demonstrate that a more pronounced IgG response is associated with specific adverse events, and these are commonly reported by health care professionals after the BNT162b2 vaccine for SARS-Cov-2.<\/jats:p>","DOI":"10.3390\/vaccines10030439","type":"journal-article","created":{"date-parts":[[2022,3,13]],"date-time":"2022-03-13T21:44:17Z","timestamp":1647207857000},"page":"439","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Short-Term Adverse Events and Antibody Response to the BNT162b2 SARS-CoV-2 Vaccine in 4156 Health Care Professionals"],"prefix":"10.3390","volume":"10","author":[{"given":"Elena","family":"Azzolini","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy"},{"name":"IRCCS Humanitas Clinical Research Hospital, via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2537-5418","authenticated-orcid":false,"given":"Lorenzo Maria","family":"Canziani","sequence":"additional","affiliation":[{"name":"IRCCS Humanitas Clinical Research Hospital, via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Voza","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy"},{"name":"IRCCS Humanitas Clinical Research Hospital, via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4674-4905","authenticated-orcid":false,"given":"Antonio","family":"Desai","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy"},{"name":"IRCCS Humanitas Clinical Research Hospital, via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1441-0145","authenticated-orcid":false,"given":"Jack","family":"Pepys","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3196-1336","authenticated-orcid":false,"given":"Maria","family":"De Santis","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy"},{"name":"IRCCS Humanitas Clinical Research Hospital, via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Ceribelli","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy"},{"name":"IRCCS Humanitas Clinical Research Hospital, via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2153-6130","authenticated-orcid":false,"given":"Chiara","family":"Pozzi","sequence":"additional","affiliation":[{"name":"IRCCS Humanitas Clinical Research Hospital, via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Turato","sequence":"additional","affiliation":[{"name":"IRCCS Humanitas Clinical Research Hospital, via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Badalamenti","sequence":"additional","affiliation":[{"name":"IRCCS Humanitas Clinical Research Hospital, via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Germagnoli","sequence":"additional","affiliation":[{"name":"IRCCS Humanitas Clinical Research Hospital, via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5578-236X","authenticated-orcid":false,"given":"Alberto","family":"Mantovani","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy"},{"name":"IRCCS Humanitas Clinical Research Hospital, via Manzoni 56, Rozzano, 20089 Milan, Italy"},{"name":"The William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Rescigno","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy"},{"name":"IRCCS Humanitas Clinical Research Hospital, via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0323-0376","authenticated-orcid":false,"given":"Carlo","family":"Selmi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy"},{"name":"IRCCS Humanitas Clinical Research Hospital, via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1056\/NEJMoa2034577","article-title":"Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine","volume":"383","author":"Polack","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.15585\/mmwr.mm6950e2","article-title":"The Advisory Committee on Immunization Practices\u2019 Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine\u2014United States, December 2020","volume":"69","author":"Oliver","year":"2020","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.15585\/mmwr.mm7038e1","article-title":"Comparative Effectiveness of Moderna, Pfizer-BioNTech, and Janssen (Johnson & Johnson) Vaccines in Preventing COVID-19 Hospitalizations Among Adults Without Immunocompromising Conditions\u2014United States, March-August 2021","volume":"70","author":"Self","year":"2021","journal-title":"MMWR Morb. Mortal. Wkly. 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Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"22848","DOI":"10.1038\/s41598-021-01930-y","article-title":"Correlates of neutralizing\/SARS-CoV-2-S1-binding antibody response with adverse effects and immune kinetics in BNT162b2-vaccinated individuals","volume":"11","author":"Maeda","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1056\/NEJMoa2020283","article-title":"Genomewide Association Study of Severe Covid-19 with Respiratory Failure","volume":"383","author":"Ellinghaus","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e01224-20","DOI":"10.1128\/JCM.01224-20","article-title":"Clinical and Analytical Performance of an Automated Serological Test That Identifies S1\/S2-Neutralizing IgG in COVID-19 Patients Semiquantitatively","volume":"58","author":"Bonelli","year":"2020","journal-title":"J. Clin. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Iguacel, I., Maldonado, A.L., Ruiz-Cabello, A.L., Casaus, M., Moreno, L.A., and Martinez-Jarreta, B. (2021). Association between COVID-19 Vaccine Side Effects and Body Mass Index in Spain. Vaccines, 9.","DOI":"10.3390\/vaccines9111321"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.vaccine.2021.11.090","article-title":"Prior COVID-19 infection is associated with increased Adverse Events (AEs) after the first, but not the second, dose of the BNT162b2\/Pfizer vaccine","volume":"40","author":"Raw","year":"2022","journal-title":"Vaccine"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1056\/NEJMoa2110345","article-title":"Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine through 6 Months","volume":"385","author":"Thomas","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1001\/jama.2021.15072","article-title":"Surveillance for Adverse Events After COVID-19 mRNA Vaccination","volume":"326","author":"Klein","year":"2021","journal-title":"JAMA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1111\/jgs.17153","article-title":"Immunogenicity after 6 months of BNT162b2 vaccination in frail or disabled nursing home residents: The COVID-A Study","volume":"69","year":"2021","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1038\/s41591-021-01325-6","article-title":"Antibody responses to the BNT162b2 mRNA vaccine in individuals previously infected with SARS-CoV-2","volume":"27","author":"Ebinger","year":"2021","journal-title":"Nat. Med."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Konstantinidis, T.G., Zisaki, S., Mitroulis, I., Konstantinidou, E., Kontekaki, E.G., Romanidou, G., Karvelas, A., Nanousi, I., Lazidis, L., and Cassimos, D. (2021). Levels of Produced Antibodies after Vaccination with mRNA Vaccine; Effect of Previous Infection with SARS-CoV-2. J. Clin. Med., 10.","DOI":"10.1101\/2021.04.05.21254934"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Goel, R.R., Apostolidis, S.A., Painter, M.M., Mathew, D., Pattekar, A., Kuthuru, O., Gouma, S., Kuri-Cervantes, L., Meng, W., and Adamski, S. (2021). Longitudinal Analysis Reveals Distinct Antibody and Memory B Cell Responses in SARS-CoV2 Naive and Recovered Individuals Following mRNA Vaccination. medRxiv.","DOI":"10.1101\/2021.03.03.21252872"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1016\/S0140-6736(21)00502-X","article-title":"Effect of previous SARS-CoV-2 infection on humoral and T-cell responses to single-dose BNT162b2 vaccine","volume":"397","author":"Prendecki","year":"2021","journal-title":"Lancet"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"100208","DOI":"10.1016\/j.lanepe.2021.100208","article-title":"Dynamics of antibody response to BNT162b2 vaccine after six months: A longitudinal prospective study","volume":"10","author":"Naaber","year":"2021","journal-title":"Lancet Reg. Health Eur."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Coggins, S.A.A., Laing, E.D., Olsen, C.H., Goguet, E., Moser, M., Jackson-Thompson, B.M., Samuels, E.C., Pollett, S.D., Tribble, D.R., and Davies, J. (2021). Adverse effects and antibody titers in response to the BNT162b2 mRNA COVID-19 vaccine in a prospective study of healthcare workers. medRxiv.","DOI":"10.1093\/ofid\/ofab575"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"794642","DOI":"10.3389\/fimmu.2021.794642","article-title":"Reactogenicity and Immunogenicity of the Pfizer and AstraZeneca COVID-19 Vaccines","volume":"12","author":"Mahallawi","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"715688","DOI":"10.3389\/fimmu.2021.715688","article-title":"Do Vaccines Need a Gender Perspective? Influenza Says Yes!","volume":"12","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1056\/NEJMoa2110475","article-title":"Safety of the BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting","volume":"385","author":"Barda","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ganga, K., Solyar, A.Y., and Ganga, R. (2021). Massive Cervical Lymphadenopathy Post-COVID-19 Vaccination. Ear Nose Throat J.","DOI":"10.1177\/01455613211048984"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Igual-Rouilleault, A.C., Soriano, I., Quan, P.L., Fernandez-Montero, A., Elizalde, A., and Pina, L. (2021). Unilateral axillary adenopathy induced by COVID-19 vaccine: US follow-up evaluation. Eur. Radiol., 1\u20138.","DOI":"10.1007\/s00330-021-08309-7"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Cohen, D., Hazut Krauthammer, S., Wolf, I., and Even-Sapir, E. (2021). A sigh of relief: Vaccine-associated hypermetabolic lymphadenopathy following the third COVID-19 vaccine dose is short in duration and uncommonly interferes with the interpretation of [(18)F]FDG PET-CT studies performed in oncologic patients. Eur. J. Nucl. Med. Mol. Imaging, 1\u20137.","DOI":"10.21203\/rs.3.rs-859072\/v1"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Baek, D.W., Hwang, S., Kim, J., Lee, J.M., Cho, H.J., Moon, J.H., Hwang, N., Jeong, J.Y., Lee, S.W., and Sohn, S.K. (2021). Patients presenting high fever with lymphadenopathy after COVID-19 vaccination were diagnosed with hemophagocytic lymphohistiocytosis. Infect. Dis., 1\u20135.","DOI":"10.1080\/23744235.2021.2010801"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Rahmani, A., Dini, G., Orsi, A., Sticchi, L., Bruzzone, B., Montecucco, A., Pellegrini, L., Manca, A., Domnich, A., and Battistini, A. (2021). Reactogenicity of BNT162b2 mRNA COVID-19 Vaccine in a Young Working Age Population: A Survey among Medical School Residents, within a Mass Vaccination Campaign, in a Regional Reference Teaching Hospital in Italy. Vaccines, 9.","DOI":"10.3390\/vaccines9111269"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Mitsikostas, D.D., Aravantinou-Fatorou, K., Deligianni, C., Kravvariti, E., Korompoki, E., Mylona, M., Vryttia, P., Papagiannopoulou, G., Delicha, E.M., and Dellis, A. (2021). Nocebo-Prone Behavior Associated with SARS-CoV-2 Vaccine Hesitancy in Healthcare Workers. Vaccines, 9.","DOI":"10.2139\/ssrn.3923449"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/3\/439\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:35:53Z","timestamp":1760135753000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/3\/439"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,13]]},"references-count":29,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["vaccines10030439"],"URL":"https:\/\/doi.org\/10.3390\/vaccines10030439","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,13]]}}}