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.

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.

SARS-CoV-2 疫苗已被证明是安全有效的。¹疫苗的总体耐受性良好，但曾有过敏反应的报道，这种反应在特应性女性和有过敏反应史的女性中更为常见。²过敏反应的报告引起了肥大细胞活化障碍 (MCAD) 患者的关注，并导致人们对疫苗犹豫不决。初步数据表明疫苗接种引起的超敏反应症状的风险较低^3-5并且在最近对 30 名接受 H1- 和 H2- 抗组胺药术前用药的克隆性肥大细胞疾病患者进行的研究中，没有人出现肥大细胞活化症状。^6个本报告的目的是在大型国际肥大细胞疾病患者队列中提供 COVID-19 疫苗接种的安全性和耐受性结果。

这是一项在美国和欧洲的三个机构进行的回顾性研究。该研究得到了每个成员机构的机构审查委员会的批准。如果在接种疫苗后 2 小时内出现症状，则认为不良反应“与疫苗有关”。根据 Brighton 过敏反应量表对症状涉及多个器官系统的患者进行评分。

共有 323 名患者接种了 666 次疫苗。根据克隆或非克隆疾病对患者进行分层。正如 Valent 等人^{7描述的 MCAS 标准}不适用于所有患者，我们将这些患者称为克隆性或非克隆性症状性肥大细胞疾病。我们的队列包括 276 名患有克隆性肥大细胞疾病的患者、18 名患有非克隆性肥大细胞疾病的患者和 29 名患有遗传性α-类胰蛋白酶血症的患者。表 1 描述了患者的人口统计数据。所有患有遗传性α-类胰蛋白酶血症的患者都接受了检查以排除克隆性肥大细胞疾病。患有克隆性肥大细胞疾病的患者不会常规接受类胰蛋白酶基因分型（HαT 检测）。大多数人接种了辉瑞 (89.0%) 疫苗，其次是摩德纳 (10.1%)、阿斯利康 (0.31%) 和强生 (0.6%)。疫苗总体耐受性良好，不良症状发生率为 40/666 (6%)。皮肤症状如瘙痒、荨麻疹和潮红最常见 (13/40, 32.5%)，其次是胃肠道症状（11/40，27.5%）、肺部症状（7/40，17.5%）和肌肉骨骼症状（2/40，5%）。图 1 以图形方式描述了不良反应。

六名患者报告了涉及一个以上器官的症状。根据 Brighton 标准对来自该患者子集的不良反应进行评分。一名患者符合过敏反应标准（布赖顿 1 级）；其他 5 人不符合布莱顿 1/2 级标准。大多数多系统不良反应发生在首次接种后 (5/6, 83%) 和辉瑞疫苗接种后 (5/6, 83%)。两名患者接受了肾上腺素。一名患者没有接受抗组胺药术前用药，也没有服用预定的 H ₁ -抗组胺药。

大多数患者在接种疫苗前进行了预先给药，80.2% 的患者接受了 H ₁ -抗组胺药。三名患者接受全身性类固醇预处理。术前用药和非术前用药患者的不良反应率在统计学上没有显着差异 ( p  = .44)，尽管很少有患者没有术前用药。许多患者还在基线时服用抗组胺药以治疗持续的肥大细胞活化障碍，这不被认为是术前用药。对于 HαT 患者，基于基因型的不良反应无统计学差异。

大多数肥大细胞疾病患者接种 COVID-19 疫苗的结果良好。没有死亡、插管或入住 ICU 的报告。与一般人群相比，不良反应的发生率更高（分别为 6% 和 2%），也高于之前关于克隆性肥大细胞活化障碍的报道。大多数反应是轻微的，涉及单一器官系统，不需要更高级别的护理。

我们还报告了与一般人群相比更高的过敏反应率。先前数据表明 0.011% 的疫苗会发生过敏反应。²一名患者符合 Brighton 1 级标准 (1/666, 0.15%)，另有 5 名患者符合 Brighton 3/4 级标准。在这些患者中，5/6 (83%) 为女性。我们没有发现疫苗类型之间不良反应发生率有任何统计学上的显着差异（例如，辉瑞与 Moderna），也没有发现因疾病类型引起的不良反应有统计学上的显着差异。

尽管使用 mRNA 和其他疫苗平台接种 COVID-19 疫苗在肥大细胞活化障碍患者中是安全且耐受性良好的，但超敏反应和过敏反应相对增加。我们建议所有患者在接种疫苗时携带肾上腺素自动注射器，并考虑在能够应对过敏反应和其他严重不良反应的中心接种疫苗。