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X-Linked TLR7 Deficiency Underlies Critical COVID-19 Pneumonia in a Male Patient with Ataxia-Telangiectasia.
Abolhassani, Hassan; Vosughimotlagh, Ahmad; Asano, Takaki; Landegren, Nils; Boisson, Bertrand; Delavari, Samaneh; Bastard, Paul; Aranda-Guillén, Maribel; Wang, Yating; Zuo, Fanglei; Sardh, Fabian; Marcotte, Harold; Du, Likun; Zhang, Shen-Ying; Zhang, Qian; Rezaei, Nima; Kämpe, Olle; Casanova, Jean-Laurent; Hammarström, Lennart; Pan-Hammarström, Qiang.
  • Abolhassani H; Department of Biosciences and Nutrition, Karolinska Institutet, 14183, Huddinge, Sweden.
  • Vosughimotlagh A; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
  • Asano T; Department of Pediatrics, North Khorasan University of Medical Sciences, Bojnurd, Iran.
  • Landegren N; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
  • Boisson B; Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
  • Delavari S; Centre for Molecular Medicine, Department of Medicine (Solna), Karolinska Institute, Stockholm, Sweden.
  • Bastard P; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
  • Aranda-Guillén M; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
  • Wang Y; University of Paris, Imagine Institute, Paris, France.
  • Zuo F; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
  • Sardh F; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
  • Marcotte H; University of Paris, Imagine Institute, Paris, France.
  • Du L; Centre for Molecular Medicine, Department of Medicine (Solna), Karolinska Institute, Stockholm, Sweden.
  • Zhang SY; Department of Biosciences and Nutrition, Karolinska Institutet, 14183, Huddinge, Sweden.
  • Zhang Q; Department of Biosciences and Nutrition, Karolinska Institutet, 14183, Huddinge, Sweden.
  • Rezaei N; Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
  • Kämpe O; Centre for Molecular Medicine, Department of Medicine (Solna), Karolinska Institute, Stockholm, Sweden.
  • Casanova JL; Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden.
  • Hammarström L; Department of Biosciences and Nutrition, Karolinska Institutet, 14183, Huddinge, Sweden.
  • Pan-Hammarström Q; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
J Clin Immunol ; 42(1): 1-9, 2022 01.
Article in English | MEDLINE | ID: covidwho-1482248
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia / Ataxia Telangiectasia / Toll-Like Receptor 7 / COVID-19 Type of study: Case report / Experimental Studies / Prognostic study Topics: Variants Limits: Child / Humans / Male Country/Region as subject: Asia Language: English Journal: J Clin Immunol Year: 2022 Document Type: Article Affiliation country: S10875-021-01151-y

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia / Ataxia Telangiectasia / Toll-Like Receptor 7 / COVID-19 Type of study: Case report / Experimental Studies / Prognostic study Topics: Variants Limits: Child / Humans / Male Country/Region as subject: Asia Language: English Journal: J Clin Immunol Year: 2022 Document Type: Article Affiliation country: S10875-021-01151-y