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Germline variants in UNC13D and AP3B1 are enriched in COVID-19 patients experiencing severe cytokine storms

Hui Luo1, Dan Liu2,3, Wenbing Liu2,3,4

  • 1Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

European Journal of Human Genetics : EJHG
|April 19, 2021
PubMed

Insights

Genetic variants in primary immunodeficiency (PID) genes, particularly UNC13D and AP3B1, are linked to severe cytokine storms and fatal outcomes in COVID-19 patients. Understanding these genetic factors improves susceptibility insights and patient management.

Area of Science:

  • Immunology
  • Genetics
  • Infectious Diseases

Background:

  • Severe COVID-19 is associated with dangerous cytokine storms, but individual susceptibility remains unclear.
  • Primary immunodeficiency (PID) genes, especially those linked to hemophagocytic lymphohistiocytosis (HLH), can dysregulate inflammatory responses.
  • HLH-related genes are known contributors to excessive cytokine storms.

Purpose of the Study:

  • To investigate the association between primary immunodeficiency (PID) gene variants and severe cytokine storms in COVID-19 patients.
  • To identify specific PID gene variants that increase vulnerability to severe COVID-19 complications.

Main Methods:

  • Whole-exome sequencing was performed on 233 hospitalized COVID-19 patients.
  • Analysis focused on identifying PID gene variants enriched in patients with severe cytokine storms.

Main Results:

  • Four PID gene variants (UNC13D, AP3B1, RNF168, DHX58) were significantly enriched in COVID-19 patients with severe cytokine storms.
  • Variants in typical HLH genes UNC13D and AP3B1 were found at much higher rates in the high-cytokine group (33.3%) compared to the low-cytokine group (5.7%).
  • Germline variants in UNC13D and AP3B1 were associated with severe cytokine storms and fatal COVID-19 outcomes.

Conclusions:

  • Germline variants in UNC13D and AP3B1 are linked to severe cytokine storms and increased mortality in COVID-19.
  • These findings enhance understanding of individual susceptibility to severe COVID-19.
  • Identifying these genetic predispositions can help optimize COVID-19 patient management.

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