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

## TL;DR

This study identifies risk factors for hospitalization due to Covid-19 in patients with X-linked agammaglobulinemia, including bronchiectasis, low IgG levels, and lack of vaccination.

## Contribution

The study identifies specific risk factors for hospitalization in XLA patients with Covid-19, including bronchiectasis, low IgG levels, and lack of vaccination.

## Key findings

- Preexisting bronchiectasis and lower IgG serum trough levels (<8 g/L) are associated with increased hospitalization risk in XLA patients with Covid-19.
- Lack of vaccination contributes to hospitalization risk in XLA patients with Covid-19.
- Ambulatory XLA patients had higher CD4+ T cell counts compared to hospitalized patients.

## 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+ 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.

The online version contains supplementary material available at 10.1007/s10875-025-01962-3.