Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19.

Autor: Zguro K; Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy., Baldassarri M; Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy.; Medical Genetics, University of Siena, 53100 Siena, Italy., Fava F; Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy.; Medical Genetics, University of Siena, 53100 Siena, Italy.; Genetica Medica, Azienda Ospedaliero-Universitaria Senese, 53100 Siena, Italy., Beligni G; Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy.; Medical Genetics, University of Siena, 53100 Siena, Italy., Daga S; Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy.; Medical Genetics, University of Siena, 53100 Siena, Italy., Leoncini R; Laboratorio Patologia Clinica, Azienda Ospedaliero-Universitaria Senese, 53100 Siena, Italy., Galasso L; Laboratorio Patologia Clinica, Azienda Ospedaliero-Universitaria Senese, 53100 Siena, Italy., Cirianni M; Laboratorio Patologia Clinica, Azienda Ospedaliero-Universitaria Senese, 53100 Siena, Italy., Rusconi S; Infectious Diseases Unit, ASST Ovest Milanese, 20025 Legnano, Italy.; Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, 20157 Milan, Italy., Siano M; Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, 20157 Milan, Italy., Francisci D; Infectious Diseases Clinic, 'Santa Maria della Misericordia' Hospital, University of Perugia, 06124 Perugia, Italy., Schiaroli E; Infectious Diseases Clinic, 'Santa Maria della Misericordia' Hospital, University of Perugia, 06124 Perugia, Italy., Luchi S; Infectious Disease Unit, Hospital of Lucca, 55100 Lucca, Italy., Morelli G; Infectious Disease Unit, Hospital of Lucca, 55100 Lucca, Italy., Martinelli E; Department of Respiratory Diseases, Azienda Ospedaliera di Cremona, 26100 Cremona, Italy., Girardis M; Department of Anesthesia and Intensive Care, University of Modena and Reggio Emilia, 41124 Modena, Italy., Busani S; Department of Anesthesia and Intensive Care, University of Modena and Reggio Emilia, 41124 Modena, Italy., Parisi SG; Department of Molecular Medicine, University of Padova, 35121 Padova, Italy., Panese S; Clinical Infectious Diseases, Mestre Hospital, 30171 Venezia, Italy., Piscopo C; Medical Genetics and Laboratory Genetics Unit, 'Antonio Cardarelli' hospital, 80131 Naples, Italy., Capasso M; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80138 Naples, Italy.; CEINGE Biotecnologie Avanzate, 80145 Naples, Italy., Tacconi D; Department of Specialized and Internal Medicine, Infectious Diseases Unit, San Donato Hospital Arezzo, 52100 Arezzo, Italy., Spertilli Raffaelli C; Department of Specialized and Internal Medicine, Infectious Diseases Unit, San Donato Hospital Arezzo, 52100 Arezzo, Italy., Giliberti A; Medical Genetics Unit, Meyer Children's University Hospital, 50134 Florence, Italy., Gori G; Medical Genetics Unit, Meyer Children's University Hospital, 50134 Florence, Italy., Katsikis PD; Department of Immunology, Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands., Lorubbio M; UOC Laboratorio Analisi Chimico Cliniche, 52100 Arezzo, Italy., Calzoni P; Laboratorio Patologia Clinica, Azienda Ospedaliero-Universitaria Senese, 53100 Siena, Italy., Ognibene A; UOC Laboratorio Analisi Chimico Cliniche, 52100 Arezzo, Italy., Bocchia M; Hematology Unit, Department of Medical Science, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy., Tozzi M; Stem Cell Transplant and Cellular Therapy Unit, University Hospital of Siena, 53100 Siena, Italy., Bucalossi A; Stem Cell Transplant and Cellular Therapy Unit, University Hospital of Siena, 53100 Siena, Italy., Marotta G; Stem Cell Transplant and Cellular Therapy Unit, University Hospital of Siena, 53100 Siena, Italy., Furini S; Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy., Gen-Covid Multicenter Study, Renieri A; Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy.; Medical Genetics, University of Siena, 53100 Siena, Italy.; Genetica Medica, Azienda Ospedaliero-Universitaria Senese, 53100 Siena, Italy., Fallerini C; Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy.; Medical Genetics, University of Siena, 53100 Siena, Italy.
Jazyk: angličtina
Zdroj: Viruses [Viruses] 2022 May 29; Vol. 14 (6). Date of Electronic Publication: 2022 May 29.
DOI: 10.3390/v14061185
Abstrakt: 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.
Databáze: MEDLINE
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