Germline variants in UNC13D and AP3B1 are enriched in COVID-19 patients experiencing severe cytokine storms.
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.
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
Similar
MEDLINE
...
LILACS
LIS