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Outcomes of COVID‐19 vaccination in 323 patients with clonal and non‐clonal mast cell activation disorders

2022; Wiley; Volume: 78; Issue: 1 Linguagem: Inglês

10.1111/all.15476

1398-9995

Matthew P. Giannetti, Francesco Olivieri, Grace Godwin, Emma Weller, Jennifer Nicoloro‐SantaBarbara, Patrizia Bonadonna, Roberta Zanotti, Giovanna Zanoni, Karin Hartmann, Mariana Castells,

Food Allergy and Anaphylaxis Research

AllergyEarly View LETTERFree Access Outcomes of COVID-19 vaccination in 323 patients with clonal and non-clonal mast cell activation disorders Matthew P. Giannetti, Corresponding Author Matthew P. Giannetti mgiannetti@bwh.harvard.edu orcid.org/0000-0003-3655-1835 Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Massachusetts, USA Harvard Medical School, Boston, Massachusetts, USA Correspondence Matthew Giannetti, Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, 60 Fenwood Road, Hale Building for Transformational Medicine, 5th floor, Boston, MA 02132, USA. Email: mgiannetti@bwh.harvard.eduSearch for more papers by this authorFrancesco Olivieri, Francesco Olivieri orcid.org/0000-0001-7854-3900 Allergy Unit, Verona University Hospital, Verona, ItalySearch for more papers by this authorGrace Godwin, Grace Godwin Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Massachusetts, USASearch for more papers by this authorEmma Weller, Emma Weller Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Massachusetts, USASearch for more papers by this authorJennifer Nicoloro-SantaBarbara, Jennifer Nicoloro-SantaBarbara Harvard Medical School, Boston, Massachusetts, USA Department of Psychiatry, Brigham and Women's, Boston, Massachusetts, USASearch for more papers by this authorPatrizia Bonadonna, Patrizia Bonadonna orcid.org/0000-0002-5703-5314 Allergy Unit, Verona University Hospital, Verona, ItalySearch for more papers by this authorRoberta Zanotti, Roberta Zanotti Department of Medicine, Section of Hematology, Verona, ItalySearch for more papers by this authorGiovanna Zanoni, Giovanna Zanoni Immunology Unit, Verona University Hospital, Verona, ItalySearch for more papers by this authorKarin Hartmann, Karin Hartmann Division of Allergy, University Hospital Basel and University of Basel, Basel, Switzerland Department of Biomedicine, University Hospital Basel and University of Basel, Basel, SwitzerlandSearch for more papers by this authorMariana Castells, Mariana Castells Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Massachusetts, USA Harvard Medical School, Boston, Massachusetts, USASearch for more papers by this author Matthew P. Giannetti, Corresponding Author Matthew P. Giannetti mgiannetti@bwh.harvard.edu orcid.org/0000-0003-3655-1835 Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Massachusetts, USA Harvard Medical School, Boston, Massachusetts, USA Correspondence Matthew Giannetti, Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, 60 Fenwood Road, Hale Building for Transformational Medicine, 5th floor, Boston, MA 02132, USA. Email: mgiannetti@bwh.harvard.eduSearch for more papers by this authorFrancesco Olivieri, Francesco Olivieri orcid.org/0000-0001-7854-3900 Allergy Unit, Verona University Hospital, Verona, ItalySearch for more papers by this authorGrace Godwin, Grace Godwin Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Massachusetts, USASearch for more papers by this authorEmma Weller, Emma Weller Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Massachusetts, USASearch for more papers by this authorJennifer Nicoloro-SantaBarbara, Jennifer Nicoloro-SantaBarbara Harvard Medical School, Boston, Massachusetts, USA Department of Psychiatry, Brigham and Women's, Boston, Massachusetts, USASearch for more papers by this authorPatrizia Bonadonna, Patrizia Bonadonna orcid.org/0000-0002-5703-5314 Allergy Unit, Verona University Hospital, Verona, ItalySearch for more papers by this authorRoberta Zanotti, Roberta Zanotti Department of Medicine, Section of Hematology, Verona, ItalySearch for more papers by this authorGiovanna Zanoni, Giovanna Zanoni Immunology Unit, Verona University Hospital, Verona, ItalySearch for more papers by this authorKarin Hartmann, Karin Hartmann Division of Allergy, University Hospital Basel and University of Basel, Basel, Switzerland Department of Biomedicine, University Hospital Basel and University of Basel, Basel, SwitzerlandSearch for more papers by this authorMariana Castells, Mariana Castells Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Massachusetts, USA Harvard Medical School, Boston, Massachusetts, USASearch for more papers by this author First published: 13 August 2022 https://doi.org/10.1111/all.15476AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat To the Editor, SARS-CoV-2 vaccines are proven to be safe and effective.1 The vaccines are overall well tolerated although hypersensitivity reactions have been reported, which are more frequent in females with atopy and those with a history of anaphylaxis.2 The reports of anaphylaxis are of concern for patients with mast cell activation disorders (MCAD) and have created vaccine hesitancy. Preliminary data indicate a low risk for vaccination-induced hypersensitivity symptoms,3-5 and in a recent study of 30 patients with clonal mast cell disorders who received H1- and H2-antihistamine premedication, none developed symptoms of mast cell activation.6 The aim of this report was to provide outcomes of the safety and tolerability of COVID-19 vaccination in a large, international cohort of patients with mast cell disorders. This was a retrospective study conducted across three institutions in the United States and Europe. The study was approved by an Institutional review board at each member institution. Adverse effects were considered “related to vaccine” if symptoms occurred within 2 h of vaccination. Patients with symptoms involving more than one organ system were scored according to the Brighton anaphylaxis scale. A total of 323 patients received 666 vaccinations. Patients were stratified based on clonal or nonclonal disorder. As MCAS criteria described by Valent et al7 were not applied to all patients, we refer to these patients as clonal or nonclonal symptomatic mast cell disorders. Our cohort included 276 patients with clonal mast cell disorders, 18 with nonclonal mast cell disorders, and 29 with hereditary alpha-tryptasemia. Table 1 describes patient demographics. All patients with hereditary alpha-tryptasemia underwent workup to exclude clonal mast cell disorders. Patients with clonal mast cell disorders did not routinely undergo tryptase genotyping (HαT testing). The majority received Pfizer (89.0%) vaccine, followed by Moderna (10.1%), Astra Zeneca (0.31%), and Johnson and Johnson (0.6%). Vaccines were overall well-tolerated with adverse symptoms occurring in 40/666 (6%). Cutaneous symptoms such as pruritus, urticaria, and flushing were most common (13/40, 32.5%), followed by gastrointestinal symptoms (11/40, 27.5%), pulmonary symptoms (7/40, 17.5%), and musculoskeletal (2/40, 5%). Figure 1 graphically depicts adverse reactions. TABLE 1. Patient demographics (n = 323) Diagnosis, % (n) Female sex Age Baseline tryptase Vaccine (Moderna/Pfizer/J&J/AZ) H1-antihistamine premedication Adverse reaction % n Mean ± SD Mean ± SD n % (n) % (n) Clonal MC disorders CM 7.1 (23) 52.2 (12) 48.1 ± 17.4 10.6 ± 13.9 4/19/0/0 47 (11) 8.5 (4) ISM− 42.4 (137) 35.0 (48) 60.0 ± 11.9 30.9 ± 58.4 4/132/0/1 86.1 (118) 5.0 (14) ISM+ 30.3 (98) 62.2 (61) 53.3 ± 12.8 45.3 ± 54.2 10/88/0/0 86.1 (85) 5.6 (11) AdvSM 4.6 (15) 40 (6) 66.3 ± 9.9 98.3 ± 124.4 2/12/0/0 60.0 (9) 12.1 (4) Nonclonal disorders mMCD 0.9 (3) 66.7 (2) 49.0 ± 6.6 11.9 ± 4.8 0/3/0/0 33.3 (1) 0.0 (0) Symptomatic MCA 5.6 (18) 61.1 (11) 56.4 ± 12.5 8.2 ± 5.4 2/16/0/0 83.3 (15) 10.8 (4) Other disorders HaT 8.9 (29) 86.2 (25) 59.8 ± 13.3 17.1 ± 4.3 9/18/2/0 69.0 (20) 7.4 (5) Abbreviations: CM, Cutaneous mastocytosis; ISM−, Indolent systemic mastocytosis without skin involvement; ISM+, Indolent systemic mastocytosis with skin involvement; mMCD, Monoclonal mast cell disorder; AdvSM, Advanced systemic mastocytosis; Symptomatic MCA, Mast cell activation disorder; HaT, Hereditary alpha-tryptasemia; J&J, Johnson and Johnson; AZ, Astra-Zeneca; n, number; MC, mast cell. FIGURE 1Open in figure viewerPowerPoint Characterization of adverse reactions to COVID-19 vaccination. (A) graphical depiction of percentage of patients with adverse reaction or no reaction. (B) Brighton Criteria scoring in adverse reactions to COVID-19 vaccination involving two or more organ systems. Six patients reported symptoms involving more than one organ. Adverse reactions from this patient subset were scored according to Brighton criteria. One patient met criteria for anaphylaxis (Brighton level 1); the other 5 did not meet Brighton level 1/2 criteria. Most multi-system adverse reactions occurred after the first dose (5/6, 83%) and after the Pfizer vaccine (5/6, 83%). Two patients were administered epinephrine. One patient did not receive antihistamine premedications and was not taking scheduled H1-antihistamines. Most patients were premedicated prior to vaccination and 80.2% received H1-antihistamines. Three patients were pretreated with systemic steroids. There was no statistically significant difference in adverse reaction rate between premedicated and non-premedicated patients (p = .44), although few patients were not premedicated. Many patients were also taking antihistamines at baseline for their ongoing mast cell activation disorders which was not considered premedication. With regard to patients with HαT, there were no statistically significant differences in adverse reactions based on genotype. Outcomes of COVID-19 vaccines were favorable in most patients with mast cell disorders. There were no reported deaths, intubations, or ICU admissions. The rate of adverse reactions was higher as compared to the general population (6% vs. 2%, respectively), as well as higher than previous reports in clonal mast cell activation disorders. Most reactions were mild, involved a single-organ system, and did not require a higher level of care. We also report a higher rate of anaphylaxis compared to the general population. Prior data indicate that anaphylaxis occurs in 0.011% of vaccines.2 One patient fulfilled Brighton Level 1 criteria (1/666, 0.15%), and five additional patients fulfilled Brighton level 3/4 criteria. Of these patients, 5/6 (83%) were female. We did not detect any statistically significant differences in rate of adverse reactions between vaccine types (e.g., Pfizer vs. Moderna) nor were there statistically significant differences of adverse reaction due to disease type. Although COVID-19 vaccination with mRNA and other vaccine platforms is safe and well-tolerated in patients with mast cell activation disorders, there is a relative increase in hypersensitivity and anaphylactic reactions. We recommended all patients carry epinephrine autoinjectors at the time of vaccination and consider receiving the vaccine at a center capable of responding to anaphylaxis and other severe adverse reactions. ACKNOWLEDGMENT We thank Mirjam Mueller, Fabian Raeber, and Seraina Schmidlin, all Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland, for excellent assistance in collecting patient data. CONFLICT OF INTEREST Matthew Giannetti receives funding from Blueprint Medicines and Cogent Biosciences. Karin Hartmann receives funding from Thermo Fisher. Mariana Castells receives funding from Blueprint Medicines and Cogent Biosciences. REFERENCES 1Klein NP, Lewis N, Goddard K, et al. Surveillance for adverse events after COVID-19 mRNA vaccination. JAMA. 2021; 326(14): 1390- 1399. doi:10.1001/jama.2021.15072CrossrefCASPubMedWeb of Science®Google Scholar 2Blumenthal KG, Robinson LB, Camargo CA Jr, et al. Acute allergic reactions to mRNA COVID-19 vaccines. JAMA. 2021; 325(15): 1562- 1564. doi:10.1001/jama.2021.2392CrossrefCASPubMedWeb of Science®Google Scholar 3Kaakati R, Khokhar D, Akin C. 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