McElvaney Oliver J, Cleary Brian, Fraughen Daniel D, Kelly Geraldine, McElvaney Oisin F, Murphy Mark P, Branagan Peter, Gunaratnam Cedric, Carroll Tomás P, Goss Christopher H, McElvaney Noel G
Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
National Centre for Alpha-1 Antitrypsin Deficiency, Beaumont Hospital, Dublin, Ireland.
Chronic Obstr Pulm Dis. 2024 Jan 25;11(1):3-12. doi: 10.15326/jcopdf.2023.0432.
Patients with alpha-1 antitrypsin deficiency (AATD) exhibit dysregulated inflammatory responses and a predilection for autoimmunity. While the adverse event (AE) profiles of COVID-19 vaccines in several chronic inflammatory conditions are now available, safety and tolerability data for patients with severe AATD have yet to be described. The feasibility of coadministering vaccines against COVID-19 and influenza in this population is similarly unclear.
We conducted a prospective study of 170 patients with PiZZ genotype AATD receiving their initial vaccination series with ChAdOx1 nCoV-19 (AstraZeneca). Patients were monitored clinically for AEs over the week that followed their first and second doses. In parallel, we conducted the same assessments in patients with PiMM genotype chronic obstructive pulmonary disease (COPD) (n=160) and PiMM individuals without lung disease (n=150). The PiZZ cohort was subsequently followed through 2 consecutive mRNA-based booster vaccines (monovalent and bivalent BNT162b2, Pfizer/BioNTech). To assess the safety of combined vaccination against COVID-19 and influenza, the quadrivalent influenza vaccine was administered to participants attending for their second COVID-19 booster vaccination, either on the same day or following a 1-week interval.
PiZZ AATD participants did not display increased AEs compared to PiMM COPD or Pi*MM non-lung disease controls. Although unexpected and serious vaccine-associated AEs did occur, the majority of AEs experienced across the 3 groups were mild and self-limiting. The AATD demographic at highest risk for AEs (especially systemic and prolonged AEs) was young females. No increase in AE risk was observed in patients with established emphysema, sonographic evidence of liver disease, or in those receiving intravenous augmentation therapy. AE incidence declined sharply following the initial vaccine series. Same-day coadministration of the COVID-19 mRNA bivalent booster vaccine and the annual influenza vaccine did not result in increased AEs compared to sequential vaccines 1 week apart.
Despite their pro-inflammatory state, patients with severe AATD are not at increased risk of AEs or serious AEs compared to patients with nonhereditary COPD and patients without lung disease. Same-day coadministration of COVID-19 booster vaccines with the annual influenza vaccine is feasible, safe, and well-tolerated in this population.
α-1抗胰蛋白酶缺乏症（AATD）患者表现出炎症反应失调且易患自身免疫性疾病。虽然现在已有几种慢性炎症性疾病中新冠病毒疫苗的不良事件（AE）情况，但严重AATD患者的安全性和耐受性数据尚未见报道。在该人群中同时接种新冠病毒疫苗和流感疫苗的可行性同样尚不明确。
我们对170例PiZZ基因型AATD患者进行了一项前瞻性研究，这些患者接受了ChAdOx1 nCoV-19（阿斯利康）的初始疫苗接种系列。在患者接种第一剂和第二剂疫苗后的一周内对其进行AE的临床监测。同时，我们对PiMM基因型慢性阻塞性肺疾病（COPD）患者（n = 160）和无肺部疾病的PiMM个体（n = 150）进行了相同的评估。随后，PiZZ队列接受了2剂连续的基于mRNA的加强疫苗（单价和二价BNT162b2，辉瑞/生物科技公司）。为评估联合接种新冠病毒疫苗和流感疫苗的安全性，在参加第二次新冠病毒加强疫苗接种的参与者中，于同一天或间隔1周接种四价流感疫苗。
与PiMM COPD或PiMM非肺部疾病对照组相比，Pi*ZZ AATD参与者未表现出AE增加。虽然确实发生了意外的严重疫苗相关AE，但3组中经历的大多数AE为轻度且自限性。AE风险最高的AATD人群特征是年轻女性。在已确诊肺气肿、有肝脏疾病超声证据的患者或接受静脉补充治疗的患者中，未观察到AE风险增加。初始疫苗接种系列后AE发生率急剧下降。与间隔1周接种的序贯疫苗相比，同一天同时接种新冠病毒mRNA二价加强疫苗和年度流感疫苗并未导致AE增加。
尽管严重AATD患者处于促炎状态，但与非遗传性COPD患者和无肺部疾病的患者相比，其发生AE或严重AE的风险并未增加。在该人群中，同一天同时接种新冠病毒加强疫苗和年度流感疫苗是可行、安全且耐受性良好的。
