{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T00:31:48Z","timestamp":1760229108067,"version":"build-2065373602"},"reference-count":27,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,5,29]],"date-time":"2022-05-29T00:00:00Z","timestamp":1653782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bando Ricerca COVID-19 Toscana","award":["B\/2020\/0119","n. 2020-2016_RIC_3","101016775","LSHM20056"],"award-info":[{"award-number":["B\/2020\/0119","n. 2020-2016_RIC_3","101016775","LSHM20056"]}]},{"name":"Intesa San Paolo","award":["B\/2020\/0119","n. 2020-2016_RIC_3","101016775","LSHM20056"],"award-info":[{"award-number":["B\/2020\/0119","n. 2020-2016_RIC_3","101016775","LSHM20056"]}]},{"name":"Ministry of Education, Universities and Research","award":["B\/2020\/0119","n. 2020-2016_RIC_3","101016775","LSHM20056"],"award-info":[{"award-number":["B\/2020\/0119","n. 2020-2016_RIC_3","101016775","LSHM20056"]}]},{"name":"Bando FISR 2020","award":["B\/2020\/0119","n. 2020-2016_RIC_3","101016775","LSHM20056"],"award-info":[{"award-number":["B\/2020\/0119","n. 2020-2016_RIC_3","101016775","LSHM20056"]}]},{"name":"H2020-SC1-FA-DTS-2018-2020","award":["B\/2020\/0119","n. 2020-2016_RIC_3","101016775","LSHM20056"],"award-info":[{"award-number":["B\/2020\/0119","n. 2020-2016_RIC_3","101016775","LSHM20056"]}]},{"name":"Health Holland","award":["B\/2020\/0119","n. 2020-2016_RIC_3","101016775","LSHM20056"],"award-info":[{"award-number":["B\/2020\/0119","n. 2020-2016_RIC_3","101016775","LSHM20056"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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\u2013platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage.<\/jats:p>","DOI":"10.3390\/v14061185","type":"journal-article","created":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T05:25:42Z","timestamp":1653974742000},"page":"1185","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19"],"prefix":"10.3390","volume":"14","author":[{"given":"Kristina","family":"Zguro","sequence":"first","affiliation":[{"name":"Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0391-1980","authenticated-orcid":false,"given":"Margherita","family":"Baldassarri","sequence":"additional","affiliation":[{"name":"Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy"},{"name":"Medical Genetics, University of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4363-2353","authenticated-orcid":false,"given":"Francesca","family":"Fava","sequence":"additional","affiliation":[{"name":"Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy"},{"name":"Medical Genetics, University of Siena, 53100 Siena, Italy"},{"name":"Genetica Medica, Azienda Ospedaliero-Universitaria Senese, 53100 Siena, 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Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Siano","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, 20157 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Francisci","sequence":"additional","affiliation":[{"name":"Infectious Diseases Clinic, \u201cSanta Maria della Misericordia\u201d Hospital, University of Perugia, 06124 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3216-4144","authenticated-orcid":false,"given":"Elisabetta","family":"Schiaroli","sequence":"additional","affiliation":[{"name":"Infectious Diseases Clinic, \u201cSanta Maria della Misericordia\u201d Hospital, University of Perugia, 06124 Perugia, 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