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10.3390/v14061185

http://scihub22266oqcxt.onion/10.3390/v14061185
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35746657!9227269!35746657
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suck abstract from ncbi


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pmid35746657      Viruses 2022 ; 14 (6): ä
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  • Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19 #MMPMID35746657
  • Zguro K; Baldassarri M; Fava F; Beligni G; Daga S; Leoncini R; Galasso L; Cirianni M; Rusconi S; Siano M; Francisci D; Schiaroli E; Luchi S; Morelli G; Martinelli E; Girardis M; Busani S; Parisi SG; Panese S; Piscopo C; Capasso M; Tacconi D; Spertilli Raffaelli C; Giliberti A; Gori G; Katsikis PD; Lorubbio M; Calzoni P; Ognibene A; Bocchia M; Tozzi M; Bucalossi A; Marotta G; Furini S; Gen-Covid Multicenter Study; Renieri A; Fallerini C
  • Viruses 2022[May]; 14 (6): ä PMID35746657show ga
  • 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.
  • |*COVID-19/genetics[MESH]
  • |*Purpura, Thrombotic Thrombocytopenic/diagnosis/genetics[MESH]
  • |ADAM Proteins/genetics/metabolism[MESH]
  • |ADAMTS13 Protein/genetics[MESH]
  • |Humans[MESH]
  • |SARS-CoV-2/pathogenicity[MESH]


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