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Germline variants in UNC13D and AP3B1 are enriched in COVID-19 patients experiencing severe cytokine storms.
Luo, Hui; Liu, Dan; Liu, Wenbing; Wang, Gaoxiang; Chen, Liting; Cao, Yang; Wei, Jia; Xiao, Min; Liu, Xin; Huang, Gang; Wang, Wei; Zhou, Jianfeng; Wang, Qian-Fei.
  • Luo H; Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • Liu D; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
  • Liu W; China National Center for Bioinformation, Beijing, China.
  • Wang G; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
  • Chen L; China National Center for Bioinformation, Beijing, China.
  • Cao Y; University of Chinese Academy of Sciences, Beijing, China.
  • Wei J; Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • Xiao M; Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • Liu X; Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • Huang G; Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • Wang W; Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • Zhou J; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
  • Wang QF; China National Center for Bioinformation, Beijing, China.
Eur J Hum Genet ; 29(8): 1312-1315, 2021 08.
Article in English | MEDLINE | ID: covidwho-1191639
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Adaptor Protein Complex 3 / Adaptor Protein Complex beta Subunits / COVID-19 / Membrane Proteins Topics: Variants Limits: Aged / Humans / Middle aged Language: English Journal: Eur J Hum Genet Journal subject: Genetics, Medical Year: 2021 Document Type: Article Affiliation country: S41431-021-00886-x

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Adaptor Protein Complex 3 / Adaptor Protein Complex beta Subunits / COVID-19 / Membrane Proteins Topics: Variants Limits: Aged / Humans / Middle aged Language: English Journal: Eur J Hum Genet Journal subject: Genetics, Medical Year: 2021 Document Type: Article Affiliation country: S41431-021-00886-x