Host genetics of pediatric SARS-CoV-2 COVID-19 and multisystem inflammatory syndrome in children

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Grant S Schulert1,2, Sydney A Blum1, Randy Q Cron3

  • 1Division of Rheumatology, Cincinnati Children's Hospital Medical Center.

Current Opinion in Pediatrics
|September 17, 2021
PubMed

Insights

Genetic factors influence severe COVID-19 pneumonia and multisystem inflammatory syndrome in children (MIS-C). Research links genes for viral entry, immune response, and cell function to severe disease in pediatric and adult populations.

Area of Science:

  • Genetics and Immunology
  • Pediatric Infectious Diseases
  • Genomic Medicine

Background:

  • Severe COVID-19 pneumonia and MIS-C are significant pediatric health concerns.
  • Understanding the genetic underpinnings of these conditions is crucial for risk stratification and treatment.
  • Previous studies have primarily focused on adult genetic associations with COVID-19.

Purpose of the Study:

  • To review and describe the genetic associations related to pediatric severe COVID-19 pneumonia.
  • To explore genetic links to the postinfectious complication, multisystem inflammatory syndrome in children (MIS-C).
  • To synthesize findings from various genetic approaches, including extrapolations from adult studies.

Main Methods:

  • Review of multiple genetic approaches, including genome-wide association studies (GWAS).
  • Analysis of whole exome sequencing (WES) and whole genome sequencing (WGS) data.
  • Examination of target gene analyses focusing on specific pathways.

Main Results:

  • GWAS identified genomic regions (e.g., HLA locus, 3p21.31) and genes (e.g., ABO, ACE2, TMPRS22) associated with severe COVID-19.
  • Type I interferon and antiviral genes (e.g., IFNAR2, TLR7) show associations with severe COVID-19.
  • WES and target gene studies revealed immune regulatory genes (e.g., SOCS1) and perforin pathway gene mutations in severe COVID-19 and MIS-C.

Conclusions:

  • Genetic associations for severe COVID-19 and MIS-C involve genes controlling viral entry, antiviral responses, and immune regulation.
  • These genetic factors play a role in lymphocyte cytolytic function and white blood cell chemotaxis.
  • Further research into genetic predispositions can enhance understanding and management of severe pediatric COVID-19 and MIS-C.
Abstract

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