1. Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19
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Zguro, Kristina, Baldassarri, Margherita, Fava, Francesca, Beligni, Giada, Daga, Sergio, Leoncini, Roberto, Galasso, Lucrezia, Cirianni, Michele, Rusconi, Stefano, Siano, Matteo, Francisci, Daniela, Schiaroli, Elisabetta, Luchi, Sauro, Morelli, Giovanna, Martinelli, Enrico, Girardis, Massimo, Busani, Stefano, Parisi, Saverio Giuseppe, Panese, Sandro, Piscopo, Carmelo, Capasso, Mario, Tacconi, Danilo, Spertilli Raffaelli, Chiara, Giliberti, Annarita, Gori, Giulia, Katsikis, Peter D, Lorubbio, Maria, Calzoni, Paola, Ognibene, Agostino, Bocchia, Monica, Tozzi, Monica, Bucalossi, Alessandro, Marotta, Giuseppe, Furini, Simone, Gen-Covid Multicenter Study, Null, Renieri, Alessandra, Fallerini, Chiara, GEN-COVID Multicenter Study, Mari, Francesca, Bruttini, Mirella, Meloni, Ilaria, Croci, Susanna, Gabriella, Doddato, Serio, VIOLA BIANCA, Mirjam, Lista, Maffeo, Debora, Pasquinelli, Elena, Ludovica, Mercuri, Brunelli, Giulia, Rossella, Tita, Maria Antonietta Mencarelli, LO RIZZO, Caterina, Pinto, ANNA MARIA, Ariani, Francesca, Montagnani, Francesca, Tumbarello, Mario, Ilaria, Rancan, Massimiliano, Fabbiani, Bargagli, Elena, Bergantini, Laura, D'Alessandro, Miriana, Cameli, Paolo, Bennett, David, Federico, Anedda, Simona, Marcantonio, Scolletta, Sabino, Franchi, Federico, Mazzei, MARIA ANTONIETTA, Susanna, Guerrini, Edoardo, Conticini, Cantarini, Luca, Frediani, Bruno, Marco, Feri, Alice, Donati, Raffaele, Scala, Luca, Guidelli, Genni, Spargi, Marta, Corridi, Cesira, Nencioni, Leonardo, Croci, Gian Piero Caldarelli, Davide, Romani, Paolo, Piacentini, Maria, Bandini, Elena, Desanctis, Silvia, Cappelli, Anna, Canaccini, Agnese, Verzuri, Valentina, Anemoli, Manola, Pisani, Alessandro, Pancrazzi, Massimo, Vaghi, Antonella D’Arminio Monforte, Federica Gaia Miraglia, Mondelli, Mario U., Stefania, Mantovani, Raffaele, Bruno, Marco, Vecchia, Marcello, Maffezzoni, Sophie, Venturelli, Andrea, Cossarizza, Andrea, Antinori, Alessandra, Vergori, Arianna, Emiliozzi, Arianna, Gabrieli, Agostino, Riva, Andrea, Tommasi, Pier Giorgio Scotton, Francesca, Andretta, Stefano, Baratti, Renzo, Scaggiante, Francesca, Gatti, Francesco, Castelli, Eugenia, Quiros-Roldan, Melania Degli Antoni, Isabella, Zanella, Matteo della Monica, Roberta, Russo, Immacolata, Andolfo, Achille, Iolascon, Giuseppe, Fiorentino, Massimo, Carella, Marco, Castori, Giuseppe, Merla, Gabriella Maria Squeo, Filippo, Aucella, Pamela, Raggi, Rita, Perna, Matteo, Bassetti, Antonio Di Biagio, Maurizio, Sanguinetti, Luca, Masucci, Alessandra, Guarnaccia, Valente, Serafina, Alex Di Florio, Mandala', Marco, Giorli, Alessia, Salerni, Lorenzo, Patrizia, Zucchi, Pierpaolo, Parravicini, Elisabetta, Menatti, Tullio, Trotta, Ferdinando, Giannattasio, Gabriella, Coiro, Fabio, Lena, Gianluca, Lacerenza, Cristina, Mussini, Luisa, Tavecchia, Lia, Crotti, Gianfranco, Parati, Roberto, Menè, Maurizio, Sanarico, Gori, Marco, Nicola, Picchiotti, Francesco, Raimondi, Alessandra, Stella, Filippo, Biscarini, Tiziana, Bachetti, Maria Teresa La Rovere, Maurizio, Bussotti, Serena, Ludovisi, Katia, Capitani, Chiara, Gabbi, Simona, Dei, Sabrina, Ravaglia, Rosangela, Artuso, Elena, Andreucci, Angelica, Pagliazzi, Erika, Fiorentini, Antonio, Perrella, Francesco, Bianchi, Paola, Bergomi, Emanuele, Catena, Riccardo, Colombo, Paola, Petrocelli, Sarah, Iacopini, Sara, Modica, Silvia, Baroni, Giulia, Micheli, Marco, Falcone, Giusy, Tiseo, Chiara, Barbieri, Tommaso, Matucci, Davide, Grassi, Claudio, Ferri, Franco, Marinangeli, Francesco, Brancati, Antonella, Vincenti, Valentina, Borgo, Stefania, Lombardi, Mirco, Lenzi, Massimo Antonio Di Pietro, Francesca, Vichi, Benedetta, Romanin, Letizia, Attala, Cecilia, Costa, Andrea, Gabbuti, Alessio, Bellucci, Marta, Colaneri, Patrizia, Casprini, Cristoforo, Pomara, Massimiliano, Esposito, Marco Antonio Bellini, Zguro, Kristina, Baldassarri, Margherita, Fava, Francesca, Beligni, Giada, Daga, Sergio, Leoncini, Roberto, Galasso, Lucrezia, Cirianni, Michele, Rusconi, Stefano, Siano, Matteo, Francisci, Daniela, Schiaroli, Elisabetta, Luchi, Sauro, Morelli, Giovanna, Martinelli, Enrico, Girardis, Massimo, Busani, Stefano, Parisi, Saverio Giuseppe, Panese, Sandro, Piscopo, Carmelo, Capasso, Mario, Tacconi, Danilo, Spertilli Raffaelli, Chiara, Giliberti, Annarita, Gori, Giulia, Katsikis, Peter D, Lorubbio, Maria, Calzoni, Paola, Ognibene, Agostino, Bocchia, Monica, Tozzi, Monica, Bucalossi, Alessandro, Marotta, Giuseppe, Furini, Simone, Gen-Covid Multicenter Study, Null, Renieri, Alessandra, Fallerini, Chiara, Gen-Covid Multicenter Study, null, and Immunology
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Thrombotic Thrombocytopenic ,Purpura, Thrombotic Thrombocytopenic ,SARS-CoV-2 ,COVID-19 ,ADAMTS13 ,thromboembolism ,add-on therapy ,ADAMTS13 Protein ,ADAM Proteins ,Infectious Diseases ,SDG 3 - Good Health and Well-being ,Virology ,von Willebrand Factor ,Humans ,Purpura - 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.
- Published
- 2022