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

Hui Luo, Dan Liu, Wenbing Liu, Gaoxiang Wang, Liting Chen, Yang Cao, Jia Wei, Min Xiao, Xin Liu, Gang Huang, Wei Wang, Jianfeng Zhou, Qian fei Wang

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Critically ill coronavirus disease 2019 (COVID-19) is characterized by severe cytokine storms, a hyperinflammatory condition intimately related to the development of fatal outcomes. Why some individuals seem particularly vulnerable to severe cytokine storms is still unknown. Primary immunodeficiency (PID)-related genes are inherited factors that dysregulate host inflammatory responses to infection, especially hemophagocytic lymphohistiocytosis (HLH)-related genes, established as contributors to the development of excessive cytokine storms. We analyzed the association between PID gene variants with severe cytokine storms in COVID-19. We conducted whole-exome sequencing in 233 hospitalized COVID-19 patients and identified four PID gene (UNC13D, AP3B1, RNF168, DHX58) variants were significantly enriched in COVID-19 patients experiencing severe cytokine storms. The total percentage of COVID-19 patients with variants in UNC13D or AP3B1, two typical HLH genes, was dramatically higher in high-level cytokine group than in low-level group (33.3 vs. 5.7%, P < 0.001). Germline variants in UNC13D and AP3B1 were associated with the development of severe cytokine storms, fatal outcomes in COVID-19. These findings advance the understanding of individual susceptibility to severe cytokine storms and help optimize the current management of COVID-19.

Original languageEnglish (US)
Pages (from-to)1312-1315
Number of pages4
JournalEuropean Journal of Human Genetics
Volume29
Issue number8
DOIs
StatePublished - Aug 2021
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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