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

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.

Automated summary

The purpose of this review is to understand the clinical outcomes of COVID-19 in monogenic causes of predominant antibody deficiency, with a focus on the antiviral contribution of humoral immunity. Key pathways related to severe COVID-19, such as BTK and hyperinflammation, are emerging, while convalescent plasma therapy has been associated with viral escape variants. XLA individuals can mount a viral-specific T-cell response, but the clinical significance is still evolving.