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.

BIH Center for Regenerative Therapies Humboldt University and Free University Berlin Germany

Center for Chronic Immunodeficiency Medical Center University of Freiburg Freiburg Germany

Clinical Unit of Infectious Diseases Microbiology and Parasitology Institute of Biomedicine of Seville University Hospital Virgen del Rocio Seville Spain

Department of Clinical Immunology and Allergology St Anne's University in Brno Brno Czechia

Department of Clinical Immunology and Transfusion Medicine Karolinska University Hospital Stockholm Sweden

Department of Clinical Immunology University Hospital Zurich Zurich Switzerland

Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden

Department of Immunology 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic

Department of Immunology and Allergology Faculty of Medicine Faculty Hospital in Pilsen Charles University Prague Pilsen Czechia

Department of Infectious Diseases Copenhagen University Hospital Rigshospitalet Copenhagen Denmark

Department of Infectious Diseases Karolinska University Hospital Stockholm Sweden

Department of Laboratory Medicine Clinical Immunology Karolinska Institutet Stockholm Sweden

Department of Molecular Medicine Sapienza University Rome Italy

Department of Rheumatology and Clinical Immunology Medical Center University of Freiburg Freiburg Germany

Division of Immunology Faculty of Medicine and Health Sciences University Medicine Oldenburg Oldenburg Germany

Division of Pediatric Allergy and Immunology Department of Medicine Johns Hopkins All Children's Hospital St Petersburg FL USA

Division of Pediatric Allergy and Immunology Department of Pediatrics University of South Florida Tampa FL USA

Division of Rheumatology and Immunology Department of Internal Medicine Medical University of Graz Graz Austria

ERN RITA Core Center RITAFIN Helsinki Finland

Faculdade de Medicina Universidade de Lisboa Lisbon Portugal

Faculty of Medicine in Hradec Kralove Charles University Hradec Kralove Czech Republic

Faculty of Medicine Masaryk University Brno Czechia

GIMM Institute for Molecular Medicine Lisbon Portugal

Infection and Immunity in Pediatric Patients Research Group Vall d'Hebron Institut de Recerca Barcelona Catalonia Spain

Inflammation Center Infectious Diseases HUS Helsinki University Hospital and University of Helsinki Helsinki Finland

Institute for Medical Immunology Charité Universitaetsmedizin Berlin Germany

Institute of Clinical Immunology and Allergy University Hospital Hradec Kralove Hradec Kralove Czech Republic

Institute of Clinical Medicine Faculty of Medicine University of Oslo Oslo Norway

Institute of Medical Genetics Faculty of Medicine and Health Sciences University Medicine Oldenburg Oldenburg Germany

Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies Barcelona Catalonia Spain

Karolinska ATMP Center Karolinska Institutet Karolinska University Hospital Stockholm Sweden

Paediatric Infectious Diseases Rheumatology and Immunology Unit Institute of Biomedicine of Seville University Hospital Virgen del Rocio University of Seville CSIC Seville Spain

Pediatric Infectious Diseases and Immunodeficiencies Unit Hospital Infantil 1 de La Dona Vall d'Hebron Vall d'Hebron Barcelona Hospital Campus Barcelona Catalonia Spain

Reference Centre for Primary Immune Deficiencies Sapienza University Hospital Policlinico Umberto 1 Rome Italy

Section of Clinical Immunology and Infectious Diseases Division of Surgery and Specialized Medicine Oslo University Hospital Oslo Norway

ULS Santa Maria Hospital de Santa Maria Lisbon Portugal

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