The association between adverse reactions and immune response against SARS-CoV-2 spike protein after vaccination with BNT162b2 among healthcare workers in a single healthcare system: a prospective observational cohort study

References

• Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–10. doi:10.1016/S0140-6736(20)30183-5.
   PubMed Web of Science ®Google Scholar
• Roser HR, Esteban O-O, Diana B, et al. Coronavirus pandemic (COVID-19) 2021 Aug 16. https://ourworldindata.org/coronavirus
   Google Scholar
• Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, Perez JL, Pérez Marc G, Moreira ED, Zerbini C, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383(27):2603–15. doi:10.1056/NEJMoa2034577.
   PubMed Web of Science ®Google Scholar
• Tang L, Hijano DR, Gaur AH, Geiger TL, Neufeld EJ, Hoffman JM, Hayden RT. Asymptomatic and symptomatic SARS-CoV-2 infections after BNT162b2 vaccination in a routinely screened workforce. Jama. 2021;325(24):2500–02. doi:10.1001/jama.2021.6564.
   PubMed Web of Science ®Google Scholar
• Hall VJ, Foulkes S, Saei A, Andrews N, Oguti B, Charlett A, Wellington E, Stowe J, Gillson N, Atti A, et al. COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): a prospective, multicentre, cohort study. Lancet. 2021;397(10286):1725–35. doi:10.1016/S0140-6736(21)00790-X.
   PubMed Web of Science ®Google Scholar
• Vasileiou E, Simpson CR, Shi T, Kerr S, Agrawal U, Akbari A, Bedston S, Beggs J, Bradley D, Chuter A, et al. Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study. Lancet. 2021;397(10285):1646–57. doi:10.1016/S0140-6736(21)00677-2.
   PubMed Web of Science ®Google Scholar
• Dagan N, Barda N, Kepten E, Miron O, Perchik S, Katz MA, Hernán MA, Lipsitch M, Reis B, Balicer RD, et al. Bnt162b2 mRNA Covid-19 vaccine in a nationwide mass vaccination setting. N Engl J Med. 2021;384(15):1412–23. doi:10.1056/NEJMoa2101765.
   PubMed Web of Science ®Google Scholar
• Angel Y, Spitzer A, Henig O, Saiag E, Sprecher E, Padova H, Ben-Ami R. Association between vaccination with BNT162b2 and incidence of symptomatic and asymptomatic SARS-CoV-2 infections among health care workers. Jama. 2021;325(24):2457–65. doi:10.1001/jama.2021.7152.
   PubMed Web of Science ®Google Scholar
• Bertollini R, Chemaitelly H, Yassine HM, Al-Thani MH, Al-Khal A, Abu-Raddad LJ. Associations of vaccination and of prior infection with positive PCR test results for SARS-CoV-2 in airline passengers arriving in Qatar. JAMA. 2021;326(2):185–88. doi:10.1001/jama.2021.9970.
   PubMed Web of Science ®Google Scholar
• Duan K, Liu B, Li C, Zhang H, Yu T, Qu J, Zhou M, Chen L, Meng S, Hu Y, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci U S A. 2020;117(17):9490–96. doi:10.1073/pnas.2004168117.
   PubMed Web of Science ®Google Scholar
• Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, Wang F, Li D, Yang M, Xing L, et al. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. Jama. 2020;323(16):1582–89. doi:10.1001/jama.2020.4783.
   PubMed Web of Science ®Google Scholar
• Feng S, Phillips DJ, White T, et al. Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection. medRxiv. 2021:21258528. doi:10.1101/2021.03.17.21253847
   Google Scholar
• Sahin U, Muik A, Vogler I, Derhovanessian E, Kranz LM, Vormehr M, Quandt J, Bidmon N, Ulges A, Baum A, et al. Bnt162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans. Nature. 2021;595(7868):572–77. doi:10.1038/s41586-021-03653-6.
   PubMed Web of Science ®Google Scholar
• Donal TS, Adam CH, and Javier G-J, et al. Two doses of SARS-CoV-2 vaccination induce more robust immune responses to emerging SARS-CoV-2 variants of concern than does natural infection. Res Sq. 2021:rs.3.rs-226857/v2. doi:10.21203/rs.3.rs-226857/v2.
   Google Scholar
• Pellini R, Venuti A, Pimpinelli F, Abril E, Blandino G, Campo F, Conti L, De Virgilio A, De Marco F, Di Domenico EG, et al. Initial observations on age, gender, BMI and hypertension in antibody responses to SARS-CoV-2 BNT162b2 vaccine. EClinicalMedicine. 2021;36:100928. doi:10.1016/j.eclinm.2021.100928.
   PubMedGoogle Scholar
• Jabal KA, Ben-Amram H, Beiruti K, et al. Impact of age, ethnicity, sex and prior infection status on immunogenicity following a single dose of the BNT162b2 mRNA COVID-19 vaccine: real-world evidence from healthcare workers, Israel, December 2020 to January 2021. Eurosurveillance. 2021;26(6):2100096.
   Web of Science ®Google Scholar
• Moderbacher CR, Ramirez SI, Dan JM, Grifoni A, Hastie KM, Weiskopf D, Belanger S, Abbott RK, Kim C, Choi J, et al. Antigen-Specific adaptive immunity to SARS-CoV-2 in acute COVID-19 and associations with age and disease severity. Cell. 2020;183(4):996–1012.e19. doi:10.1016/j.cell.2020.09.038.
   PubMed Web of Science ®Google Scholar
• Braun J, Loyal L, Frentsch M, Wendisch D, Georg P, Kurth F, Hippenstiel S, Dingeldey M, Kruse B, Fauchere F, et al. SARS-CoV-2-Reactive T cells in healthy donors and patients with COVID-19. Nature. 2020;587(7833):270–74. doi:10.1038/s41586-020-2598-9.
   PubMed Web of Science ®Google Scholar
• Chapin-Bardales J, Gee J, Myers T. Reactogenicity following receipt of mRNA-based COVID-19 vaccines. JAMA. 2021;325(21):2201–02. doi:10.1001/jama.2021.5374.
   PubMed Web of Science ®Google Scholar
• Sprent J, King C. COVID-19 vaccine side effects: the positives about feeling bad. Sci Immunol. 2021;6(60):eabj9256. doi:10.1126/sciimmunol.abj9256.
   PubMed Web of Science ®Google Scholar
• Doedée AM, Boland GJ, Pennings JL, de Klerk A, Berbers GAM, van der Klis FRM, de Melker HE, van Loveren H, Janssen R, et al. Effects of prophylactic and therapeutic paracetamol treatment during vaccination on hepatitis B antibody levels in adults: two open-label, randomized controlled trials. PLoS One. 2014;9(6):e98175. doi:10.1371/journal.pone.0098175.
   PubMed Web of Science ®Google Scholar
• Prymula R, Siegrist C-A, Chlibek R, Zemlickova H, Vackova M, Smetana J, Lommel P, Kaliskova E, Borys D, Schuerman L, et al. Effect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: two open-label, randomised controlled trials. Lancet. 2009;374(9698):1339–50. doi:10.1016/S0140-6736(09)61208-3.
   PubMed Web of Science ®Google Scholar
• Hwang YH, Song KH, Choi Y, Go S, Choi S-J, Jung J, Kang CK, Choe PG, Kim N-J, Park WB, et al. Can reactogenicity predict immunogenicity after COVID-19 vaccination? Korean J Intern Med. 2021;36:1486–91. kjim.2021.210. doi:10.3904/kjim.2021.210.
   PubMed Web of Science ®Google Scholar
• Takeuchi M, Higa Y, and Esaki A, et al. Does reactogenicity after a second injection of the BNT162b2 vaccine predict spike IgG antibody levels in healthy Japanese subjects? medRxiv. 2021;21258444. doi:10.1101/2021.06.08.21258444.
   Google Scholar
• Maeda K, Amano M, Uemura Y, Tsuchiya K, Matsushima T, Noda K, Shimizu Y, Fujiwara A, Takamatsu Y, Ichikawa Y, et al. Correlates of neutralizing/sars-CoV-2-S1-binding antibody response with adverse effects and immune kinetics in BNT162b2-vaccinated individuals. medRxiv. 2021:21261237. doi:10.1101/2021.07.27.21261237
   Google Scholar
• Coggins SAA, Laing ED, Olsen CH, Goguet E, Moser M, Jackson-Thompson BM, Samuels EC, Pollett SD, Tribble DR, Davies J, et al. Adverse effects and antibody titers in response to the BNT162b2 mRNA COVID-19 vaccine in a prospective study of healthcare workers. medRxiv. 2021:21259544. doi:10.1101/2021.06.25.21259544
   Google Scholar
• Rechavi Y, Shashar M, Lellouche J, Yana M, Yakubovich D, Sharon N. Occurrence of BNT162b2 vaccine adverse reactions is associated with enhanced SARS-CoV-2 IgG antibody response. Vaccines (Basel). 2021;9(9). doi:10.3390/vaccines9090977.
   PubMed Web of Science ®Google Scholar
• Debes AK, Xiao S, Colantuoni E, Egbert ER, Caturegli P, Gadala A, Milstone AM. Association of vaccine type and prior SARS-CoV-2 infection with symptoms and antibody measurements following vaccination among health care workers. JAMA Intern Med. 2021;181(12):1660–62. doi:10.1001/jamainternmed.2021.4580.
   PubMed Web of Science ®Google Scholar
• Abbott. Abbott ARCHITECT SARS-CoV-2 IgG II Quant Reagent Instructions for Use 2021. 2021 Aug 16. https://www.corelaboratory.abbott/int/en/offerings/segments/infectious-disease/sars-cov-2-
   Google Scholar
• Narasimhan M, Mahimainathan L, Araj E, Clark AE, Markantonis J, Green A, Xu J, SoRelle JA, Alexis C, Fankhauser K, et al. Clinical evaluation of the Abbott alinity SARS-CoV-2 spike-specific quantitative IgG and IgM assays among infected, recovered, and vaccinated groups. J Clin Microbiol. 2021;59(7):e00388–21. doi: 10.1128/JCM.00388-21.
   PubMed Web of Science ®Google Scholar
• U. S. Food and Drug Administration. EUA authorized serology test performance 2022. 2022 Jan 5. https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/eua-authorized-serology-test-performance
   Google Scholar
• Aiello A, Najafi Fard S, Petruccioli E, Petrone L, Vanini V, Farroni C, Cuzzi G, Navarra A, Gualano G, Mosti S, et al. Spike is the most recognized antigen in the whole-blood platform in both acute and convalescent COVID-19 patients. Int J Infect Dis. 2021;106:338–47. doi:10.1016/j.ijid.2021.04.034.
   PubMed Web of Science ®Google Scholar
• R Core team. R: the R project for statistical computing 2021. 2021 Aug 16. https://www.r-project.org/
   Google Scholar
• Gastwirth JL, Gel YR, Hui WL, et al. Lawstat: tools for biostatistics, public policy, and law: Comprehensive R Archive Network (CRAN); 2021 Sep 4. https://cran.r-project.org/web/packages/lawstat/index.html
   Google Scholar
• Wickham H, Averick M, Bryan J, Chang W, McGowan L, François R, Grolemund G, Hayes A, Henry L, Hester J, et al. Welcome to the tidyverse. J Open Source Software. 2019;4:1686. doi:10.21105/joss.01686.
   Google Scholar
• Mitani A, Horie T, Yokoyama R, Nakano Y, Hamada K, Inoue Y, Saito M, Ishii T, Sunohara M, Takahashi R, et al. Interpretations of SARS-CoV-2 IgM and IgG antibody titers in the seroepidemiological study of asymptomatic healthy volunteers. J Infect Chemother. 2022 ;28(2):266–72. doi:10.1016/j.jiac.2021.11.020.
   PubMed Web of Science ®Google Scholar
• Jalkanen P, Kolehmainen P, Häkkinen HK, Huttunen M, Tähtinen PA, Lundberg R, Maljanen S, Reinholm A, Tauriainen S, Pakkanen SH, et al. COVID-19 mRNA vaccine induced antibody responses against three SARS-CoV-2 variants. Nat Commun. 2021;12(1):3991. doi:10.1038/s41467-021-24285-4.
   PubMed Web of Science ®Google Scholar
• Zani A, Caccuri F, Messali S, Bonfanti C, Caruso A. Serosurvey in BNT162b2 vaccine-elicited neutralizing antibodies against authentic B.1, B.1.1.7, B.1.351, B.1.525 and P.1 SARS-CoV-2 variants. Emerg Microbes Infect. 2021;10(1):1241–43. doi:10.1080/22221751.2021.1940305.
   PubMed Web of Science ®Google Scholar
• Juhn YJ. Risks for infection in patients with asthma (or other atopic conditions): is asthma more than a chronic airway disease? J Allergy Clin Immunol. 2014;134(2):247–59. doi:10.1016/j.jaci.2014.04.024.
   PubMed Web of Science ®Google Scholar
• Timmermann CA, Osuna CE, Steuerwald U, Weihe P, Poulsen LK, Grandjean P. Asthma and allergy in children with and without prior measles, mumps, and rubella vaccination. Pediatr Allergy Immunol. 2015;26(8):742–49. doi:10.1111/pai.12391.
   PubMed Web of Science ®Google Scholar
• Bednarek A, Bodajko-Grochowska A, Klepacz R, Szczekala K, Zarzycka D, Emeryk A. Clinical form of asthma and vaccine immunityin preschoolers. Postepy Dermatol Alergol. 2021;38(1):123–30. doi:10.5114/ada.2021.104287.
   PubMed Web of Science ®Google Scholar
• Romeo J, Wärnberg J, Nova E, Díaz LE, Gómez-Martinez S, Marcos A. Moderate alcohol consumption and the immune system: a review. Br J Nutr. 2007;98(Suppl 1):S111–5. doi:10.1017/S0007114507838049.
   PubMedGoogle Scholar
• Barr T, Helms C, Grant K, Messaoudi I. Opposing effects of alcohol on the immune system. Prog Neuropsychopharmacol Biol Psychiatry. 2016;65:242–51. doi:10.1016/j.pnpbp.2015.09.001.
   PubMed Web of Science ®Google Scholar
• Kageyama T, Ikeda K, Tanaka S, Taniguchi T, Igari H, Onouchi Y, Kaneda A, Matsushita K, Hanaoka H, Nakada T-A, et al. Antibody responses to BNT162b2 mRNA COVID-19 vaccine and their predictors among healthcare workers in a tertiary referral hospital in Japan. Clin Microbiol Infect. 2021: j.cmi.2021.07.042. doi:10.1016/j.cmi.2021.07.042.
   PubMed Web of Science ®Google Scholar
• Pfizer/BioNtech. Pfizer and BioNtech provide update on booster program in light of the delta-variant 2021; [accessed 2021 Jul 8; 2021 Sep 2]. https://cdn.pfizer.com/pfizercom/2021-07/Delta_Variant_Study_Press_Statement_Final_7.8.21.pdf?IPpR1xZjlwvaUMQ9sRn2FkePcBiRPGqw
   Google Scholar
• Van Praet JT, Vandecasteele S, De Roo A, De Vriese AS, Reynders M. Humoral and cellular immunogenicity of the BNT162b2 messenger RNA Coronavirus disease 2019 vaccine in nursing home residents. Clin Infect Dis. 2021;73:ciab300. doi:10.1093/cid/ciab300.
   PubMed Web of Science ®Google Scholar
• Oberhardt V, Luxenburger H, Kemming J, Schulien I, Ciminski K, Giese S, Csernalabics B, Lang-Meli J, Janowska I, Staniek J, et al. Rapid and stable mobilization of CD8+ T cells by SARS-CoV-2 mRNA vaccine. Nature. 2021;597(7875):268–73. doi:10.1038/s41586-021-03841-4.
   PubMed Web of Science ®Google Scholar
• Monforte A, Tavelli A, Perrone PM, Za A, Razzini K, Tomasoni D, Bordoni V, Romanò L, Orfeo N, Marchetti G, et al. Association between previous infection with SARS CoV-2 and the risk of self-reported symptoms after mRNA BNT162b2 vaccination: data from 3,078 health care workers. EClinicalMedicine. 2021;36:100914. doi:10.1016/j.eclinm.2021.100914.
   PubMedGoogle Scholar