{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T14:02:27Z","timestamp":1775743347632,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T00:00:00Z","timestamp":1644796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Research Foundation - Flanders","doi-asserted-by":"publisher","award":["1805518N"],"award-info":[{"award-number":["1805518N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>The reported incidence of immediate hypersensitivity reactions (IHR) including anaphylaxis after COVID-19 vaccination is 10-fold higher than for other vaccines. Several patient groups are theorized to be at particular risk. Since specific vaccination guidelines for these patients are based on expert opinion, we performed a retrospective monocentric analysis of the tolerability of adenoviral vector and mRNA-based COVID-19 vaccines in a cohort of patients allegedly at high risk of IHR. Reactions were assessed immediately on-site by allergists during a monitored vaccination protocol and after 3\u20137 days through telephone interviews. The cohort included 196 patients (aged 12\u201384 years) with primary mast cell disease (pMCD, 50.5%), idiopathic anaphylaxis (IA, 19.9%), hereditary angioedema (HAE, 5.1%) or miscellaneous indications (24.5%). Twenty-five immediate reactions were observed in 221 vaccine doses (11.3%). Most occurred in IA or miscellaneous patients. None fulfilled anaphylaxis criteria and most were mild and self-limiting. Reaction occurrence was significantly associated with female sex. In total, 13.5% of pMCD patients reported mast cell activation-like symptoms within 72 h post-vaccination. All pediatric pMCD patients (n = 9, 12\u201318 years) tolerated both mRNA-based vaccine doses. In summary, adenoviral vector and mRNA-based COVID-19 vaccines were safe and well-tolerated in patients with pMCD, HAE, and IA. No anaphylaxis was observed. The mild and subjective nature of most reactions suggests a nocebo effect associated with vaccination in a medicalized setting. Patients with pMCD could experience mild flare-ups of mast cell activation-like symptoms, supporting antihistamine premedication.<\/jats:p>","DOI":"10.3390\/vaccines10020286","type":"journal-article","created":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T03:52:27Z","timestamp":1644810747000},"page":"286","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["COVID-19 Vaccination Safety and Tolerability in Patients Allegedly at High Risk for Immediate Hypersensitivity Reactions"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7217-0629","authenticated-orcid":false,"given":"Toon","family":"Ieven","sequence":"first","affiliation":[{"name":"Department of General Internal Medicine, Division of Allergy and Clinical Immunology, University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Allergy and Clinical Immunology Research Group, Department of Microbiology, Immunology and Transplantation, Katholieke Universiteit Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martijn","family":"Vandebotermet","sequence":"additional","affiliation":[{"name":"Department of General Internal Medicine, Division of Allergy and Clinical Immunology, University Hospitals Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7388-2249","authenticated-orcid":false,"given":"Lisa","family":"Nuyttens","sequence":"additional","affiliation":[{"name":"Allergy and Clinical Immunology Research Group, Department of Microbiology, Immunology and Transplantation, Katholieke Universiteit Leuven, 3000 Leuven, Belgium"},{"name":"Department of Pediatrics, University Hospitals Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Devolder","sequence":"additional","affiliation":[{"name":"Pharmacy Department, University Hospitals Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Vandenberghe","sequence":"additional","affiliation":[{"name":"Department of Hematology, University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Laboratory for Genetics of Malignant Disorders, KU Leuven Department of Human Genetics, Katholieke Universiteit Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique","family":"Bullens","sequence":"additional","affiliation":[{"name":"Allergy and Clinical Immunology Research Group, Department of Microbiology, Immunology and Transplantation, Katholieke Universiteit Leuven, 3000 Leuven, Belgium"},{"name":"Department of Pediatrics, University Hospitals Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4261-6220","authenticated-orcid":false,"given":"Rik","family":"Schrijvers","sequence":"additional","affiliation":[{"name":"Department of General Internal Medicine, Division of Allergy and Clinical Immunology, University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Allergy and Clinical Immunology Research Group, Department of Microbiology, Immunology and Transplantation, Katholieke Universiteit Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1001\/jama.2021.0600","article-title":"Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Pfizer-BioNTech COVID-19 Vaccine","volume":"325","author":"Shimabukuro","year":"2021","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/j.jaci.2015.07.048","article-title":"Risk of anaphylaxis after vaccination in children and adults","volume":"137","author":"McNeil","year":"2016","journal-title":"J. Allerg. Clin. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4398","DOI":"10.1016\/j.vaccine.2015.07.035","article-title":"Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS)","volume":"33","author":"Shimabukuro","year":"2015","journal-title":"Vaccine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1111\/cea.13874","article-title":"Polyethylene glycol (PEG) is a cause of anaphylaxis to the Pfizer\/BioNTech mRNA COVID-19 vaccine","volume":"51","author":"Sellaturay","year":"2021","journal-title":"Clin. Exp. Allerg."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Habran, M., Vandebotermet, M., and Schrijvers, R. (2021). Polyethylene glycol allergy and immediate-type hypersensivitity reaction to COVID-19 vaccination: Case report. J. Investig. Allergol. Clin. Immunol., 32.","DOI":"10.18176\/jiaci.0740"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1016\/j.jaci.2021.04.002","article-title":"Potential mechanisms of anaphylaxis to COVID-19 mRNA vaccines","volume":"147","author":"Risma","year":"2021","journal-title":"J. Allerg. Clin. Immunol."},{"key":"ref_7","unstructured":"(2021, November 16). Risicostratificatie Voor Allergische Reacties bij COVID-19 Vaccinatie. Brussels: Belgian Superior Health Council (hgr). Available online: https:\/\/d34j62pglfm3rr.cloudfront.net\/downloads\/procedure+specifieke+doelgroepen_anafylaxie-NL.pdf."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Tanno, L.K., Berard, F., Beaudoin, E., and Didier, A. (2021). SARS-CoV-2 Vaccination and Anaphylaxis: Recommendations of the French Allergy Community and the Montpellier World Health Organization Collaborating Center. Vaccines, 9.","DOI":"10.3390\/vaccines9060560"},{"key":"ref_9","unstructured":"(2021, November 16). COVID-19: The Green Book, Chapter 14a. London: Public Health England (PHE), Available online: https:\/\/www.gov.uk\/government\/publications\/covid-19-the-green-book-chapter-14a."},{"key":"ref_10","unstructured":"(2021, November 16). Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Approved or Authorized in the United States. Washington, DC: US Centers for Disease Control (CDC), Available online: https:\/\/www.cdc.gov\/vaccines\/covid-19\/clinical-considerations\/covid-19-vaccines-us.html#Appendix-B."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2139","DOI":"10.1016\/j.jaip.2021.03.041","article-title":"COVID-19 Vaccination in Mastocytosis: Recommendations of the European Competence Network on Mastocytosis (ECNM) and American Initiative in Mast Cell Diseases (AIM)","volume":"9","author":"Bonadonna","year":"2021","journal-title":"J. Allerg. Clin. Immunol. Pract."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1182\/blood-2016-09-731893","article-title":"Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts","volume":"129","author":"Valent","year":"2017","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1111\/j.1365-2362.2007.01807.x","article-title":"Standards and standardization in mastocytosis: Consensus statements on diagnostics, treatment recommendations and response criteria","volume":"37","author":"Valent","year":"2007","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1111\/all.13384","article-title":"The international WAO\/EAACI guideline for the management of hereditary angioedema-The 2017 revision and update","volume":"73","author":"Maurer","year":"2018","journal-title":"Allergy"},{"key":"ref_15","first-page":"S2198","article-title":"Tolerability of polysorbate 80-containing COVID-19 vaccines in confirmed polyethylene glycol-allergic patients","volume":"21","author":"Ieven","year":"2021","journal-title":"J. Allerg. Clin. Immunol. Pract."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/0952-8180(94)00001-K","article-title":"The post-anesthesia recovery score revisited","volume":"7","author":"Aldrete","year":"1995","journal-title":"J. Clin. Anesth."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1159\/000501079","article-title":"Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome","volume":"180","author":"Valent","year":"2019","journal-title":"Int. Arch. Allerg. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5675","DOI":"10.1016\/j.vaccine.2007.02.064","article-title":"Anaphylaxis: Case definition and guidelines for data collection, analysis, and presentation of immunization safety data","volume":"25","author":"Gold","year":"2007","journal-title":"Vaccine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s40413-015-0080-1","article-title":"2015 update of the evidence base: World Allergy Organization anaphylaxis guidelines","volume":"8","author":"Simons","year":"2015","journal-title":"World Allerg. Organ. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1001\/jama.2021.3976","article-title":"Acute Allergic Reactions to mRNA COVID-19 Vaccines","volume":"325","author":"Blumenthal","year":"2021","journal-title":"JAMA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.ajic.2021.10.015","article-title":"The Safety profile of COVID-19 vaccinations in the United States","volume":"50","author":"Singh","year":"2022","journal-title":"Am. J. Infect. Control."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s13223-021-00613-7","article-title":"Anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines: A systematic review and meta-analysis","volume":"17","author":"Alhumaid","year":"2021","journal-title":"Allerg. Asthma Clin. Immunol."},{"key":"ref_23","first-page":"703","article-title":"Safety and side effect profile of Pfizer-BioNTech COVID-19 vaccination among healthcare workers: A tertiary hospital experience in Singapore","volume":"50","author":"Lim","year":"2021","journal-title":"Ann. Acad. Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Wi, Y.M., Kim, S.H., and Peck, K.R. (2021). Early Adverse Events between mRNA and Adenovirus-Vectored COVID-19 Vaccines in Healthcare Workers. Vaccines, 9.","DOI":"10.3390\/vaccines9080931"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e2122255","DOI":"10.1001\/jamanetworkopen.2021.22255","article-title":"Prevalence of Allergic Reactions After Pfizer-BioNTech COVID-19 Vaccination Among Adults With High Allergy Risk","volume":"4","author":"Shavit","year":"2021","journal-title":"JAMA Netw. Open."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.jaci.2021.01.004","article-title":"mRNA COVID-19 vaccine is well tolerated in patients with cutaneous and systemic mastocytosis with mast cell activation symptoms and anaphylaxis","volume":"147","author":"Rama","year":"2021","journal-title":"J. Allerg. Clin. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3198","DOI":"10.1016\/j.jaip.2021.05.010","article-title":"Safety of COVID-19 vaccination in patients with mastocytosis and monoclonal mast cell activation syndrome","volume":"9","author":"Kaakati","year":"2021","journal-title":"J. Allerg. Clin. Immunol. Pract."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1016\/j.jaip.2019.02.002","article-title":"Mast Cell Activation Syndrome and Mastocytosis: Initial Treatment Options and Long-Term Management","volume":"7","author":"Castells","year":"2019","journal-title":"J. Allerg. Clin. Immunol. Pract."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1111\/cea.12882","article-title":"Vaccination management in children and adults with mastocytosis","volume":"47","author":"Zanoni","year":"2017","journal-title":"Clin. Exp. Allerg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1111\/all.14739","article-title":"YEAACI statement on the diagnosis, management and prevention of severe allergic reactions to COVID-19 vaccines","volume":"76","author":"Sokolowska","year":"2021","journal-title":"Allergy"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/2\/286\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:18:55Z","timestamp":1760134735000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/2\/286"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,14]]},"references-count":30,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["vaccines10020286"],"URL":"https:\/\/doi.org\/10.3390\/vaccines10020286","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,14]]}}}