TY - JOUR
T1 - Germline variants in UNC13D and AP3B1 are enriched in COVID-19 patients experiencing severe cytokine storms
AU - Luo, Hui
AU - Liu, Dan
AU - Liu, Wenbing
AU - Wang, Gaoxiang
AU - Chen, Liting
AU - Cao, Yang
AU - Wei, Jia
AU - Xiao, Min
AU - Liu, Xin
AU - Huang, Gang
AU - Wang, Wei
AU - Zhou, Jianfeng
AU - Wang, Qian fei
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85104352408
UR - https://www.scopus.com/pages/publications/85104352408#tab=citedBy
U2 - 10.1038/s41431-021-00886-x
DO - 10.1038/s41431-021-00886-x
M3 - Article
C2 - 33867526
AN - SCOPUS:85104352408
SN - 1018-4813
VL - 29
SP - 1312
EP - 1315
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 8
ER -