Royal College of Surgeons in Ireland
Safety and Reactogenicity of Coronavirus Disease 2019 Vaccination in Severe Alpha-1 Antitrypsin Deficiency.pdf (961.83 kB)

Safety and reactogenicity of coronavirus disease 2019 vaccination in severe alpha-1 antitrypsin deficiency

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posted on 2024-05-30, 15:52 authored by Oliver McElvaney, Brian ClearyBrian Cleary, Daniel Fraughen, Geraldine Kelly, Oisin F McElvaney, Mark MurphyMark Murphy, Peter BranaganPeter Branagan, Cedric GunaratnamCedric Gunaratnam, Tomas CarrollTomas Carroll, Christopher H Goss, Noel G McElvaneyNoel G McElvaney
Background: 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.
Methods: We conducted a prospective study of 170 patients with Pi*ZZ 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 Pi*MM genotype chronic obstructive pulmonary disease (COPD) (n=160) and Pi*MM individuals without lung disease (n=150). The Pi*ZZ 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.
Results: Pi*ZZ AATD participants did not display increased AEs compared to Pi*MM 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.
Conclusions: 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.


Elaine Galwey Memorial Research Bursary

National Institutes of Health (P30 DK089507, UL1TR000423)



This is an Accepted Manuscript of an article published by Taylor & Francis in Chronic Obstructive Pulmonary Diseases on 6 September 2023, available online:

Published Citation

McElvaney OJ. et al. Safety and reactogenicity of COVID-19 vaccination in severe alpha-1 antitrypsin deficiency. Chronic Obstr Pulm Dis. 2024;11(1):3-12.

Publication Date

25 January 2024

PubMed ID



  • Beaumont Hospital
  • Medicine


COPD Foundation


  • Accepted Version (Postprint)