Bronchiectasis, Low IgG Levels and Lack of Vaccination are Risk Factors for Covid-19 Hospitalization in X-linked Agammaglobulinemia – A Retrospective Multicenter Study

X-linked agammaglobulinemia (XLA) is caused by loss-of-function variants in Bruton's tyrosine kinase, leading to absence of circulating B lymphocytes and inability to produce antibodies. Despite the fear that patients with XLA would be at high risk for severe infection when the novel virus SARS-CoV-2 emerged in the society with low pre-existing immunity, most patients with XLA did not suffer from severe disease. However, some patients were critically affected. Factors associated with hospitalization in patients with XLA remain poorly described. Thus, we designed a study to determine risk factors associated with hospitalization due to Covid-19 in patients with XLA. Data was collected from 17 sites in Europe and the US, comprising n = 81 patients, with hospitalization due to SARS-CoV-2 infection in 14 patients. Nearly 17% of patients with XLA required hospitalization due to Covid-19, but only 3 patients had ventilatory support. After correcting for the effect of the date of infection during the early pandemic, univariate and multiple logistic regression analysis showed that preexisting bronchiectasis and lower IgG serum trough levels (< 8 g/L) before infection were associated with an increased risk for hospitalization, with a high rate of superinfection. The lack of vaccination seemed to contribute to this risk, and ambulatory patients had higher amounts of CD4<sup>+</sup> T cells before infection compared to hospitalized patients. Thus, our data suggests a need for IgG trough levels above 8 g/L, especially in patients with bronchiectasis, to protect patients with XLA during viral infections such as Covid-19 and reduce morbidity due to superinfections.

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Journal
Journal of Clinical Immunology
Published
2025-11-15
DOI
https://doi.org/10.1007/s10875-025-01962-3
Primary Topic
Immunodeficiency and Autoimmune Disorders
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article
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article

Bronchiectasis, Low IgG Levels and Lack of Vaccination are Risk Factors for Covid-19 Hospitalization in X-linked Agammaglobulinemia – A Retrospective Multicenter Study

Jiří Litzman, Olaf Neth, Timi Martelius, Anna Šedivá et al.
Journal of Clinical Immunology
Immunodeficiency and Autoimmune Disorders
article

Bronchiectasis, Low IgG Levels and Lack of Vaccination are Risk Factors for Covid-19 Hospitalization in X-linked Agammaglobulinemia – A Retrospective Multicenter Study

Jiří Litzman, Olaf Neth, Timi Martelius, Anna Šedivá, Jolán E. Walter, Pavlína Králíčková, Federica Pulvirenti, Ivana Malkusová, Smith Rjh, Hannes Lindahl, Cláudia Varandas, Børre Fevang, Susana L. Silva, Cinzia Milito, Cristina Roca-Oporto, Klaus Warnatz, Leif G. Hanitsch, Jacques G. Rivière, Christoph B. Geier, Urs C. Steiner, Terese L. Katzenstein, Isabel Hodl, Serena Shaffren, Rahim Miller, Caroline Stenlander, Emelie Wahren-Borgström
article en

Abstract

X-linked agammaglobulinemia (XLA) is caused by loss-of-function variants in Bruton's tyrosine kinase, leading to absence of circulating B lymphocytes and inability to produce antibodies. Despite the fear that patients with XLA would be at high risk for severe infection when the novel virus SARS-CoV-2 emerged in the society with low pre-existing immunity, most patients with XLA did not suffer from severe disease. However, some patients were critically affected. Factors associated with hospitalization in patients with XLA remain poorly described. Thus, we designed a study to determine risk factors associated with hospitalization due to Covid-19 in patients with XLA. Data was collected from 17 sites in Europe and the US, comprising n = 81 patients, with hospitalization due to SARS-CoV-2 infection in 14 patients. Nearly 17% of patients with XLA required hospitalization due to Covid-19, but only 3 patients had ventilatory support. After correcting for the effect of the date of infection during the early pandemic, univariate and multiple logistic regression analysis showed that preexisting bronchiectasis and lower IgG serum trough levels (< 8 g/L) before infection were associated with an increased risk for hospitalization, with a high rate of superinfection. The lack of vaccination seemed to contribute to this risk, and ambulatory patients had higher amounts of CD4<sup>+</sup> T cells before infection compared to hospitalized patients. Thus, our data suggests a need for IgG trough levels above 8 g/L, especially in patients with bronchiectasis, to protect patients with XLA during viral infections such as Covid-19 and reduce morbidity due to superinfections.

Journal of Clinical ImmunologyVol. 45(1)
Oslo University Hospital (NO), Carl von Ossietzky Universität Oldenburg (DE), Karolinska University Hospital (SE), University of Helsinki (FI), University of Lisbon (PT), Johns Hopkins University (US), University of Freiburg (DE), University of Oslo (NO), Medical University of Graz (AT), Charles University (CZ), Masaryk University (CZ), University of South Florida (US), Policlinico Umberto I (IT), Helsinki University Hospital (FI), University Medical Center Freiburg (DE), Copenhagen University Hospital (DK), Rigshospitalet (DK), Karolinska Institutet (SE), Johns Hopkins All Children's Hospital (US), University Hospital of Zurich (CH), Vall d'Hebron Institut de Recerca (ES), Klinikum Oldenburg (DE), Berlin-Brandenburger Centrum für Regenerative Therapien (DE), Vall d'Hebron Hospital Universitari (ES), Instituto de Biomedicina de Sevilla (ES), St. Anne's University Hospital Brno (CZ), University Hospital Hradec Králové (CZ), Institute of Molecular Medicine (IN), Hospital de Santa Maria (PT), Jeffrey Modell Foundation (AU), University of Hradec Králové (CZ), Charité - Universitätsmedizin Berlin (DE), Sapienza University of Rome (IT)
Bundesministerium für Bildung und Forschung, Karolinska Institutet, Vetenskapsrådet, Stockholm läns landsting
Openalex Percentile: Top 63%
Immunodeficiency and Autoimmune Disorders
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