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. 2024 Jan 25;11(1):3-12.
doi: 10.15326/jcopdf.2023.0432.

Safety and Reactogenicity of COVID-19 Vaccination in Severe Alpha-1 Antitrypsin Deficiency

Oliver J McElvaney  1   2   3   4 , Brian Cleary  1 , Daniel D Fraughen  1   2 , Geraldine Kelly  5 , Oisin F McElvaney  1 , Mark P Murphy  1 , Peter Branagan  1   2 , Cedric Gunaratnam  1   2 , Tomás P Carroll  1   5 , Christopher H Goss  3   4   6 , Noel G McElvaney  1   2
Affiliations

Safety and Reactogenicity of COVID-19 Vaccination in Severe Alpha-1 Antitrypsin Deficiency

Oliver J McElvaney et al. Chronic Obstr Pulm Dis. .

Abstract

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.

Keywords: COVID-19; alpha-1 antitrypsin deficiency; influenza; safety; vaccine.

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Conflict of interest statement

OJMcE has been an investigator for Chiesi and Grifols. CHG has been an investigator for Boehringer Ingelheim and a drug safety monitoring board chair for Novartis. NGMcE has been an investigator in clinical trials for CSL Behring, Galapagos, Chiesi, and Vertex, and reports personal fees, all outside the present unfunded work, from CSL Behring, Grifols, Chiesi, and Shire. The remaining authors have no conflicts to disclose.

References

    1. Crystal RG,Brantly ML,Hubbard RC,Curiel DT,States DJ,Holmes MD. The alpha-1 antitrypsin gene and its mutations: clinical consequences and strategies for therapy. Chest. 1989;95:196-208. doi: https://doi.org/10.1378/chest.95.1.196 - PubMed
    1. Brantly M,Nukiwa T,Crystal RG. Molecular basis of alpha-1 antitrypsin deficiency. Am J Med. 1988;84(6):13-31. Suppl1. doi: https://doi.org/10.1016/S0002-9343(88)80066-4 - PubMed
    1. Carrell RW,Lomas DA. Alpha-1 antitrypsin deficiency - a model for conformational diseases. N Engl J Med. 2002;346:45-53. doi: https://doi.org/10.1056/NEJMra010772 - PubMed
    1. Lomas DA,Evans DL,Finch JT,Carrell RW. The mechanism of Z alpha-1 antitrypsin accumulation in the liver. Nature. 1992;357:605-607. doi: https://doi.org/10.1038/357605a0 - PubMed
    1. Gadek JE,Klein HG,Holland PV,Crystal RG. Replacement therapy of alpha-1 antitrypsin deficiency. Reversal of protease-antiprotease imbalance within the alveolar structures of PiZ subjects. J Clin Invest. 1981;68:1158-1165. doi: https://doi.org/10.1172/JCI110360 - PMC - PubMed