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TBK1 and TNFRSF13B mutations and an autoinflammatory disease in a child with lethal COVID-19

Axel Schmidt1, Sophia Peters1, Alexej Knaus2

  • 1Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.

NPJ Genomic Medicine
|July 2, 2021
PubMed

Insights

A child with an autoinflammatory disorder experienced a severe, fatal case of COVID-19. Genetic variants in TBK1 and TNFRSF13B likely contributed to the severe presentation of coronavirus disease (COVID-19).

Area of Science:

  • Immunology
  • Genetics
  • Pediatrics

Background:

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are typically mild in children.
  • An autoinflammatory disorder and its immunosuppressive treatment (prednisolone, methotrexate) were noted in the patient.
  • The child's parents were consanguineous (half cousins) of Turkish descent.

Purpose of the Study:

  • To describe an unusual and severe case of coronavirus disease (COVID-19) in a pediatric patient.
  • To investigate the genetic underpinnings of the severe COVID-19 presentation in this child.

Main Methods:

  • Case report detailing clinical presentation and progression.
  • Trio exome sequencing was performed to identify genetic variants.

Main Results:

  • The patient presented with severe symptoms including seizures, cardiac insufficiency, and multi-organ failure, ultimately leading to death.
  • Trio exome sequencing revealed a homozygous splice-variant in TBK1 and a homozygous missense variant in TNFRSF13B.
  • TBK1 variants are linked to severe COVID-19, and TNFRSF13B variants are associated with common variable immunodeficiency (CVID).

Conclusions:

  • The identified genetic variants (TBK1, TNFRSF13B), the patient's autoinflammatory disorder, and its treatment likely contributed to the lethal outcome of COVID-19.
  • This case highlights potential genetic predispositions to severe coronavirus disease (COVID-19) in children, especially those with underlying immune conditions.

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