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COVID-19 and X-linked agammaglobulinemia (XLA) - insights from a monogenic antibody deficiency

Lookup NU author(s): Dr Ben ShillitoeORCiD, Professor Andrew GenneryORCiD



This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.PURPOSE OF REVIEW: The clinical outcomes from COVID-19 in monogenic causes of predominant antibody deficiency have pivotal implications for our understanding of the antiviral contribution of humoral immunity. This review summarizes the lessons learned from COVID-19 infection in X-linked agammaglobulinemia (XLA) due to genetic defects in Bruton's tyrosine kinase (BTK). RECENT FINDINGS: Key molecular pathways underlying the development of severe COVID-19 are emerging, highlighting the possible contribution of BTK to hyperinflammation. SARS-CoV-2 specific T-cell responses and complement activation appear insufficient to achieve viral clearance in some B-cell deficient individuals. Whilst appearing efficacious in this group, use of convalescent plasma has been recently associated with the evolution of viral escape variants. Early data suggests individuals with XLA can mount a viral-specific T-cell vaccine response, however, the clinical significance of this is still emerging. SUMMARY: In contrast to reports made early in the pandemic, we show XLA patients remain susceptible to severe disease. Persistent infection was common and is likely to carry a significant symptom burden and risk of novel variant evolution. COVID-19 infection in this vulnerable, antibody deficient group due to genetic, therapeutic or disease causes may require prompt and specific intervention for both patient and societal benefit.

Publication metadata

Author(s): Ponsford MJ, Shillitoe BMJ, Humphreys IR, Gennery AR, Jolles S

Publication type: Article

Publication status: Published

Journal: Current Opinion in Allergy and Clinical Immunology

Year: 2021

Volume: 21

Issue: 6

Pages: 525-534

Print publication date: 01/12/2021

Acceptance date: 02/04/2020

Date deposited: 04/01/2022

ISSN (print): 1528-4050

ISSN (electronic): 1473-6322

Publisher: Lippincott Williams & Wilkins


DOI: 10.1097/ACI.0000000000000792

PubMed id: 34596095


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