X-Linked TLR7 Deficiency Underlies Critical COVID-19 Pneumonia in a Male Patient with Ataxia-Telangiectasia.

Abstract

BACKGROUND:

Coronavirus disease 2019 (COVID-19) exhibits a wide spectrum of clinical manifestations, ranging from asymptomatic to critical conditions. Understanding the mechanism underlying life-threatening COVID-19 is instrumental for disease prevention and treatment in individuals with a high risk.

OBJECTIVES:

We aimed to identify the genetic cause for critical COVID-19 pneumonia in a patient with a preexisting inborn error of immunity (IEI).

METHODS:

Serum levels of specific antibodies against the virus and autoantibodies against type I interferons (IFNs) were measured. Whole exome sequencing was performed, and the impacts of candidate gene variants were investigated. We also evaluated 247 ataxia-telangiectasia (A-T) patients in the Iranian IEI registry.

RESULTS:

We report a 7-year-old Iranian boy with a preexisting hyper IgM syndrome who developed critical COVID-19 pneumonia. IgM only specific COVID-19 immune response was detected but no autoantibodies against type I IFN were observed. A homozygous deleterious mutation in the ATM gene was identified, which together with his antibody deficiency, radiosensitivity, and neurological signs, established a diagnosis of A-T. Among the 247 A-T patients evaluated, 36 had SARS-CoV-2 infection, but all had mild symptoms or were asymptomatic except the index patient. A hemizygous deleterious mutation in the TLR7 gene was subsequently identified in the patient.

CONCLUSIONS:

We report a unique IEI patient with combined ATM and TLR7 deficiencies. The two genetic defects underlie A-T and critical COVID-19 in this patient, respectively.

• Authors: Hassan Abolhassani, Ahmad Vosughimotlagh, Takaki Asano, Nils Landegren, Bertrand Boisson, Samaneh Delavari, Paul Bastard, Maribel Aranda-Guillén, Yating Wang, Fanglei Zuo, Fabian Sardh, Harold Marcotte, Likun Du, Shen-Ying Zhang, Qian Zhang, Nima Rezaei, Olle Kämpe, Jean-Laurent Casanova, Lennart Hammarström, Qiang Pan-Hammarström
• Journal: Journal of clinical immunology (J Clin Immunol) Vol. 42 Issue 1 Pg. 1-9 (01 2022) ISSN: 1573-2592 [Electronic] Netherlands
• PMID: 34686943 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• TLR7 protein, human
• Toll-Like Receptor 7

Topics

• Ataxia Telangiectasia (genetics)
• COVID-19 (genetics)
• Child
• Humans
• Iran
• Male
• Pneumonia (genetics)
• Toll-Like Receptor 7 (deficiency, genetics)