Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19.
Viruses
; 14(6)2022 05 29.
Article
in English
| MEDLINE | ID: covidwho-1869825
ABSTRACT
Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Purpura, Thrombotic Thrombocytopenic
/
COVID-19
Type of study:
Cohort study
/
Diagnostic study
/
Observational study
/
Prognostic study
Topics:
Variants
Limits:
Humans
Language:
English
Year:
2022
Document Type:
Article
Affiliation country:
V14061185
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