Genomewide Association Study of Severe Covid-19 with Respiratory Failure


Por: Ellinghaus, D, Degenhardt, F, Bujanda, L, Buti, M, Albillos, A, Invernizzi, P, Fernandez, J, Prati, D, Baselli, G, Asselta, R, Grimsrud, MM, Milani, C, Aziz, F, Kassens, J, May, S, Wendorff, M, Wienbrandt, L, Uellendahl-Werth, F, Zheng, TH, Yi, XL, de Pablo, R, Chercoles, AG, Palom, A, Garcia-Fernandez, AE, Rodriguez-Frias, F, Zanella, A, Bandera, A, Protti, A, Aghemo, A, Lleo, A, Biondi, A, Caballero-Garralda, A, Gori, A, Tanck, A, Nolla, AC, Latiano, A, Fracanzani, AL, Peschuck, A, Julia, A, Pesenti, A, Voza, A, Jimenez, D, Mateos, B, Jimenez, BN, Quereda, C, Paccapelo, C, Gassner, C, Angelini, C, Cea, C, Solier, A, Pestana, D, Muniz-Diaz, E, Sandoval, E, Paraboschi, EM, Navas, E, Sanchez, FG, Ceriotti, F, Martinelli-Boneschi, F, Peyvandi, F, Blasi, F, Tellez, L, Blanco-Grau, A, Hemmrich-Stanisak, G, Grasselli, G, Costantino, G, Cardamone, G, Foti, G, Aneli, S, Kurihara, H, ElAbd, H, My, I, Galvan-Femenia, I, Martin, J, Erdmann, J, Ferrusquia-Acosta, J, Garcia-Etxebarria, K, Izquierdo-Sanchez, L, Bettini, LR, Sumoy, L, Terranova, L, Moreira, L, Santoro, L, Scudeller, L, Mesonero, F, Roade, L, Ruhlemann, MC, Schaefer, M, Carrabba, M, Riveiro-Barciela, M, Basso, MEF, Valsecchi, MG, Hernandez-Tejero, M, Acosta-Herrera, M, D'Angio, M, Baldini, M, Cazzaniga, M, Schulzky, M, Cecconi, M, Wittig, M, Ciccarelli, M, Rodriguez-Gandia, M, Bocciolone, M, Miozzo, M, Montano, N, Braun, N, Sacchi, N, Martinez, N, Ozer, O, Palmieri, O, Faverio, P, Preatoni, P, Bonfanti, P, Omodei, P, Tentorio, P, Castro, P, Rodrigues, PM, Blandino, A, de Cid, R, Ferrer, R, Gualtierotti, R, Nieto, R, Goerg, S, Badalamenti, S, Marsal, S, Matullo, G, Pelusi, S, Juzenas, S, Aliberti, S, Monzani, V, Moreno, V, Wesse, T, Lenz, TL, Pumarola, T, Rimoldi, V, Bosari, S, Albrecht, W, Peter, W, Romero-Gomez, M, D'Amato, M, Duga, S, Banales, JM, Hov, JR, Folseraas, T, Valenti, L, Franke, A and Karlsen, TH

Publicada: 15 oct 2020
Resumen:
BackgroundThere is considerable variation in disease behavior among patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19). Genomewide association analysis may allow for the identification of potential genetic factors involved in the development of Covid-19. MethodsWe conducted a genomewide association study involving 1980 patients with Covid-19 and severe disease (defined as respiratory failure) at seven hospitals in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe. After quality control and the exclusion of population outliers, 835 patients and 1255 control participants from Italy and 775 patients and 950 control participants from Spain were included in the final analysis. In total, we analyzed 8,582,968 single-nucleotide polymorphisms and conducted a meta-analysis of the two case-control panels. ResultsWe detected cross-replicating associations with rs11385942 at locus 3p21.31 and with rs657152 at locus 9q34.2, which were significant at the genomewide level (P<5x10(-8)) in the meta-analysis of the two case-control panels (odds ratio, 1.77; 95% confidence interval [CI], 1.48 to 2.11; P=1.15x10(-10); and odds ratio, 1.32; 95% CI, 1.20 to 1.47; P=4.95x10(-8), respectively). At locus 3p21.31, the association signal spanned the genes SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1. The association signal at locus 9q34.2 coincided with the ABO blood group locus; in this cohort, a blood-group-specific analysis showed a higher risk in blood group A than in other blood groups (odds ratio, 1.45; 95% CI, 1.20 to 1.75; P=1.48x10(-4)) and a protective effect in blood group O as compared with other blood groups (odds ratio, 0.65; 95% CI, 0.53 to 0.79; P=1.06x10(-5)). ConclusionsWe identified a 3p21.31 gene cluster as a genetic susceptibility locus in patients with Covid-19 with respiratory failure and confirmed a potential involvement of the ABO blood-group system. (Funded by Stein Erik Hagen and others.) During the peak of hospitalizations of patients with severe Covid-19 in Italy and Spain in March, a group of researchers in these and other countries obtained and analyzed samples, resulting in the identification of two chromosomal loci associated with the disorder.

Filiaciones:
Ellinghaus, D:
 Univ Kiel, Inst Clin Mol Biol, Rosalind Franklin Str 12, D-24105 Kiel, Germany

 Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Prot Res, Dis Syst Biol, Copenhagen, Denmark

Degenhardt, F:
 Univ Kiel, Inst Clin Mol Biol, Rosalind Franklin Str 12, D-24105 Kiel, Germany

Bujanda, L:
 Univ Basque Country, Dept Liver & Gastrointestinal Dis, Biodonostia Hlth Res Inst, Donostia Univ Hospital, San Sebastian, Spain

 Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain

Buti, M:
 Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain

 Univ Barcelona, Hosp Univ Vall dHebron, Liver Unit, Hosp Clin,Dept Internal Med, Vall dHebron Barcelona Hosp Campus, Barcelona, Spain

 Univ Autonoma Barcelona, Bellaterra, Spain

Albillos, A:
 Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain

 Univ Alcala, Hosp Univ Ramon y Cajal, Inst Ramon y Cajal Invest Sanitaria, Dept Gastroenterol, Madrid, Spain

Invernizzi, P:
 Univ Milano Bicocca, Div Gastroenterol, Dept Med & Surg, Ctr Autoimmune Liver Dis, Milan, Italy

 San Gerardo Hosp, European Reference Network Hepatol Dis, Monza, Italy

Fernandez, J:
 August Pi & Sunyer Biomed Res Inst, Barcelona, Spain

 European Fdn Study Chron Liver Failure, Barcelona, Spain

Prati, D:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

Baselli, G:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

Asselta, R:
 Humanitas Univ, Dept Biomed Sci, Milan, Italy

 IRCCS, Humanitas Clin & Res Ctr, Milan, Italy

Grimsrud, MM:
 Oslo Univ Hosp, Div Surg Inflammatory Dis & Transplantat, Dept Transplantat Med, Rikshospitalet,Norwegian PSC Res Ctr, Oslo, Norway

 Oslo Univ Hosp, Internal Med Res Inst, Div Surg Inflammatory Dis & Transplantat, Rikshospitalet, Oslo, Norway

 Univ Oslo, Postboks 4950 Nydalen, N-0424 Oslo, Norway

Milani, C:
 Univ Milano Bicocca, Div Gastroenterol, Dept Med & Surg, Ctr Autoimmune Liver Dis, Milan, Italy

 San Gerardo Hosp, European Reference Network Hepatol Dis, Monza, Italy

Aziz, F:
 August Pi & Sunyer Biomed Res Inst, Barcelona, Spain

Kassens, J:
 Univ Kiel, Inst Clin Mol Biol, Rosalind Franklin Str 12, D-24105 Kiel, Germany

May, S:
 Univ Kiel, Inst Clin Mol Biol, Rosalind Franklin Str 12, D-24105 Kiel, Germany

Wendorff, M:
 Univ Kiel, Inst Clin Mol Biol, Rosalind Franklin Str 12, D-24105 Kiel, Germany

Wienbrandt, L:
 Univ Kiel, Inst Clin Mol Biol, Rosalind Franklin Str 12, D-24105 Kiel, Germany

Uellendahl-Werth, F:
 Univ Kiel, Inst Clin Mol Biol, Rosalind Franklin Str 12, D-24105 Kiel, Germany

Zheng, TH:
 Monash Univ, Sch Biol Sci, Clayton, Vic, Australia

Yi, XL:
 Univ Kiel, Inst Clin Mol Biol, Rosalind Franklin Str 12, D-24105 Kiel, Germany

de Pablo, R:
 Univ Alcala, Hosp Univ Ramon y Cajal, Inst Ramon y Cajal Invest Sanitaria, Dept Intens Care, Madrid, Spain

Chercoles, AG:
 Donostialdea Integrated Hlth Org, Osakidetza Basque Hlth Serv, Clin Biochem Dept, San Sebastian, Spain

Palom, A:
 Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain

 Univ Barcelona, Hosp Univ Vall dHebron, Liver Unit, Hosp Clin,Dept Internal Med, Vall dHebron Barcelona Hosp Campus, Barcelona, Spain

 Vall dHebron Inst Recerca, Barcelona, Spain

Garcia-Fernandez, AE:
 Autonomous Univ Barcelona, Univ Hosp Vall dHebron, Immunohematol Dept, Dept Biochem,Banc Sang & Teixits, Barcelona, Spain

Rodriguez-Frias, F:
 Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain

 Vall dHebron Inst Recerca, Barcelona, Spain

 Autonomous Univ Barcelona, Univ Hosp Vall dHebron, Immunohematol Dept, Dept Biochem,Banc Sang & Teixits, Barcelona, Spain

 Univ Autonoma Barcelona, Bellaterra, Spain

Zanella, A:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

 Univ Milan, Milan, Italy

Bandera, A:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

 Univ Milan, Milan, Italy

Protti, A:
 Humanitas Univ, Dept Biomed Sci, Milan, Italy

 IRCCS, Humanitas Clin & Res Ctr, Milan, Italy

Aghemo, A:
 Humanitas Univ, Dept Biomed Sci, Milan, Italy

 IRCCS, Humanitas Clin & Res Ctr, Milan, Italy

Lleo, A:
 Humanitas Univ, Dept Biomed Sci, Milan, Italy

 IRCCS, Humanitas Clin & Res Ctr, Milan, Italy

Biondi, A:
 Univ Milano Bicocca, Fdn MBBM Osped, Pediat Dept, San Gerardo, Italy

 Univ Milano Bicocca, Fdn MBBM Osped, European Reference Network PaedCan, EuroBloodNet,MetabERN,Ctr Tettamanti, San Gerardo, Italy

Caballero-Garralda, A:
 Autonomous Univ Barcelona, Univ Hosp Vall dHebron, Immunohematol Dept, Dept Biochem,Banc Sang & Teixits, Barcelona, Spain

Gori, A:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

 Univ Milan, Milan, Italy

Tanck, A:
 Univ Kiel, Inst Clin Mol Biol, Rosalind Franklin Str 12, D-24105 Kiel, Germany

Nolla, AC:
 Germans Trias & Pujol Res Inst, GenomesForLife GCAT Lab Grp, Badalona, Spain

Latiano, A:
 Fdn IRCCS Casa Sollievo Sofferenza, Gastroenterol Unit, San Giovanni Rotondo, Italy

Fracanzani, AL:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

 Univ Milan, Milan, Italy

Peschuck, A:
 Univ Kiel, Inst Clin Mol Biol, Rosalind Franklin Str 12, D-24105 Kiel, Germany

Julia, A:
 Vall dHebron Inst Recerca, Barcelona, Spain

Pesenti, A:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

 Univ Milan, Milan, Italy

Voza, A:
 IRCCS, Humanitas Clin & Res Ctr, Milan, Italy

Jimenez, D:
 Univ Alcala, Hosp Univ Ramon y Cajal, Inst Ramon y Cajal Invest Sanitaria, Dept Resp Dis, Madrid, Spain

Mateos, B:
 Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain

 Univ Alcala, Hosp Univ Ramon y Cajal, Inst Ramon y Cajal Invest Sanitaria, Dept Gastroenterol, Madrid, Spain

Jimenez, BN:
 Donostialdea Integrated Hlth Org, Osakidetza Basque Hlth Serv, Clin Biochem Dept, San Sebastian, Spain

Quereda, C:
 Univ Alcala, Hosp Univ Ramon y Cajal, Inst Ramon y Cajal Invest Sanitaria, Dept Infect Dis, Madrid, Spain

Paccapelo, C:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

Gassner, C:
 Univ Kiel, Inst Clin Mol Biol, Rosalind Franklin Str 12, D-24105 Kiel, Germany

 Private Univ Principal Liechtenstein, Vilnius, Lithuania

Angelini, C:
 IRCCS, Humanitas Clin & Res Ctr, Milan, Italy

Cea, C:
 Autonomous Univ Barcelona, Univ Hosp Vall dHebron, Immunohematol Dept, Dept Biochem,Banc Sang & Teixits, Barcelona, Spain

Solier, A:
 Univ Alcala, Hosp Univ Ramon y Cajal, Inst Ramon y Cajal Invest Sanitaria, Dept Resp Dis, Madrid, Spain

Pestana, D:
 Univ Alcala, Hosp Univ Ramon y Cajal, Inst Ramon y Cajal Invest Sanitaria, Dept Anesthesiol, Madrid, Spain

Muniz-Diaz, E:
 Autonomous Univ Barcelona, Univ Hosp Vall dHebron, Immunohematol Dept, Banc Sang & Teixits, Barcelona, Spain

Sandoval, E:
 August Pi & Sunyer Biomed Res Inst, Barcelona, Spain

Paraboschi, EM:
 Humanitas Univ, Dept Biomed Sci, Milan, Italy

 IRCCS, Humanitas Clin & Res Ctr, Milan, Italy

Navas, E:
 Univ Alcala, Hosp Univ Ramon y Cajal, Inst Ramon y Cajal Invest Sanitaria, Dept Infect Dis, Madrid, Spain

Sanchez, FG:
 Ctr Transfus Madrid, Histocompatibilidad & Biol Mol, Madrid, Spain

Ceriotti, F:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

Martinelli-Boneschi, F:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

 Univ Milan, Milan, Italy

Peyvandi, F:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

 Univ Milan, Milan, Italy

Blasi, F:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

 Univ Milan, Milan, Italy

Tellez, L:
 Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain

 Univ Alcala, Hosp Univ Ramon y Cajal, Inst Ramon y Cajal Invest Sanitaria, Dept Gastroenterol, Madrid, Spain

Blanco-Grau, A:
 Univ Alcala, Hosp Univ Ramon y Cajal, Inst Ramon y Cajal Invest Sanitaria, Dept Intens Care, Madrid, Spain

 Autonomous Univ Barcelona, Univ Hosp Vall dHebron, Immunohematol Dept, Dept Biochem,Banc Sang & Teixits, Barcelona, Spain

Hemmrich-Stanisak, G:
 Univ Kiel, Inst Clin Mol Biol, Rosalind Franklin Str 12, D-24105 Kiel, Germany

Grasselli, G:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

 Univ Milan, Milan, Italy

Costantino, G:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

 Univ Milan, Milan, Italy

Cardamone, G:
 Humanitas Univ, Dept Biomed Sci, Milan, Italy

Foti, G:
 Univ Milano Bicocca, Dept Emergency Anesthesia & Intens Care, Milan, Italy

Aneli, S:
 Univ Torino, Dept Med Sci, Turin, Italy

Kurihara, H:
 IRCCS, Humanitas Clin & Res Ctr, Milan, Italy

My, I:
 IRCCS, Humanitas Clin & Res Ctr, Milan, Italy

:
 Germans Trias & Pujol Res Inst, GenomesForLife GCAT Lab Grp, Badalona, Spain

Martin, J:
 Inst Parasitol & Biomed Lopez Neyra, Granada, Spain

Erdmann, J:
 Univ Lubeck, Inst Cardiogenet, Lubeck, Germany

 German Res Ctr Cardiovasc Res, Partner Site Hamburg Lubeck Kiel, Lubeck, Germany

 Univ Heart Ctr Lubeck, Lubeck, Germany

Ferrusquia-Acosta, J:
 August Pi & Sunyer Biomed Res Inst, Barcelona, Spain

Garcia-Etxebarria, K:
 Univ Basque Country, Dept Liver & Gastrointestinal Dis, Biodonostia Hlth Res Inst, Donostia Univ Hospital, San Sebastian, Spain

 Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain

Izquierdo-Sanchez, L:
 Univ Basque Country, Dept Liver & Gastrointestinal Dis, Biodonostia Hlth Res Inst, Donostia Univ Hospital, San Sebastian, Spain

 Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain

Bettini, LR:
 Univ Milano Bicocca, Fdn MBBM Osped, Pediat Dept, San Gerardo, Italy

 Univ Milano Bicocca, Fdn MBBM Osped, European Reference Network PaedCan, EuroBloodNet,MetabERN,Ctr Tettamanti, San Gerardo, Italy

:
 Germans Trias & Pujol Res Inst, High Content Genom & Bioinformat Unit, Badalona, Spain

Terranova, L:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

Moreira, L:
 August Pi & Sunyer Biomed Res Inst, Barcelona, Spain

Santoro, L:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

Scudeller, L:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

Mesonero, F:
 Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain

 Univ Alcala, Hosp Univ Ramon y Cajal, Inst Ramon y Cajal Invest Sanitaria, Dept Gastroenterol, Madrid, Spain

Roade, L:
 Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain

 Univ Barcelona, Hosp Univ Vall dHebron, Liver Unit, Hosp Clin,Dept Internal Med, Vall dHebron Barcelona Hosp Campus, Barcelona, Spain

Ruhlemann, MC:
 Univ Kiel, Inst Clin Mol Biol, Rosalind Franklin Str 12, D-24105 Kiel, Germany

Schaefer, M:
 Stefan Morsch Stiftung, Birkenfeld, Germany

Carrabba, M:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

Riveiro-Barciela, M:
 Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain

 Univ Barcelona, Hosp Univ Vall dHebron, Liver Unit, Hosp Clin,Dept Internal Med, Vall dHebron Barcelona Hosp Campus, Barcelona, Spain

 Univ Autonoma Barcelona, Bellaterra, Spain

Basso, MEF:
 Univ Kiel, Inst Clin Mol Biol, Rosalind Franklin Str 12, D-24105 Kiel, Germany

Valsecchi, MG:
 Ctr Bioinformat Biostat & Bioimaging, Milan, Italy

Hernandez-Tejero, M:
 August Pi & Sunyer Biomed Res Inst, Barcelona, Spain

Acosta-Herrera, M:
 Inst Parasitol & Biomed Lopez Neyra, Granada, Spain

D'Angio, M:
 Univ Milano Bicocca, Fdn MBBM Osped, Pediat Dept, San Gerardo, Italy

 Univ Milano Bicocca, Fdn MBBM Osped, European Reference Network PaedCan, EuroBloodNet,MetabERN,Ctr Tettamanti, San Gerardo, Italy

Baldini, M:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

Cazzaniga, M:
 Univ Milano Bicocca, Phase 1 Res Ctr, Sch Med & Surg, Milan, Italy

Schulzky, M:
 Univ Kiel, Inst Clin Mol Biol, Rosalind Franklin Str 12, D-24105 Kiel, Germany

Cecconi, M:
 Humanitas Univ, Dept Biomed Sci, Milan, Italy

 IRCCS, Humanitas Clin & Res Ctr, Milan, Italy

Wittig, M:
 Univ Kiel, Inst Clin Mol Biol, Rosalind Franklin Str 12, D-24105 Kiel, Germany

Ciccarelli, M:
 IRCCS, Humanitas Clin & Res Ctr, Milan, Italy

Rodriguez-Gandia, M:
 Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain

 Univ Alcala, Hosp Univ Ramon y Cajal, Inst Ramon y Cajal Invest Sanitaria, Dept Gastroenterol, Madrid, Spain

Bocciolone, M:
 IRCCS, Humanitas Clin & Res Ctr, Milan, Italy

Miozzo, M:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

 Univ Milan, Milan, Italy

Montano, N:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

 Univ Milan, Milan, Italy

Braun, N:
 Univ Kiel, Inst Clin Mol Biol, Rosalind Franklin Str 12, D-24105 Kiel, Germany

 Univ Hosp Schleswig Holstein, Campus Kiel, Kiel, Germany

Sacchi, N:
 EO Osped Galliera, Italian Bone Marrow Donor Registry, Genoa, Italy

Martinez, N:
 Univ Alcala, Hosp Univ Ramon y Cajal, Inst Ramon y Cajal Invest Sanitaria, Dept Anesthesiol, Madrid, Spain

Ozer, O:
 Max Planck Inst Evolutionary Biol, Res Grp Evolutionary Immunogen, Plon, Germany

Palmieri, O:
 Fdn IRCCS Casa Sollievo Sofferenza, Gastroenterol Unit, San Giovanni Rotondo, Italy

Faverio, P:
 Univ Milano Bicocca, Dept Pneumol, Milan, Italy

Preatoni, P:
 IRCCS, Humanitas Clin & Res Ctr, Milan, Italy

Bonfanti, P:
 Univ Milano Bicocca, Dept Infect Dis, Milan, Italy

 San Gerardo Hosp, Infect Dis Unit, Monza, Italy

Omodei, P:
 IRCCS, Humanitas Clin & Res Ctr, Milan, Italy

Tentorio, P:
 IRCCS, Humanitas Clin & Res Ctr, Milan, Italy

Castro, P:
 August Pi & Sunyer Biomed Res Inst, Barcelona, Spain

Rodrigues, PM:
 Univ Basque Country, Dept Liver & Gastrointestinal Dis, Biodonostia Hlth Res Inst, Donostia Univ Hospital, San Sebastian, Spain

 Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain

:
 Germans Trias & Pujol Res Inst, GenomesForLife GCAT Lab Grp, Badalona, Spain

Ferrer, R:
 Autonomous Univ Barcelona, Univ Hosp Vall dHebron, Immunohematol Dept, Dept Intens Care,Banc Sang & Teixits, Barcelona, Spain

Gualtierotti, R:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

 Univ Milan, Milan, Italy

Nieto, R:
 Univ Alcala, Hosp Univ Ramon y Cajal, Inst Ramon y Cajal Invest Sanitaria, Dept Resp Dis, Madrid, Spain

Goerg, S:
 Univ Hosp Schleswig Holstein, Inst Transfus Med, Lubeck, Germany

Badalamenti, S:
 IRCCS, Humanitas Clin & Res Ctr, Milan, Italy

Marsal, S:
 Vall dHebron Inst Recerca, Barcelona, Spain

Matullo, G:
 Univ Torino, Dept Med Sci, Turin, Italy

Pelusi, S:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

 Univ Milan, Milan, Italy

Juzenas, S:
 Univ Kiel, Inst Clin Mol Biol, Rosalind Franklin Str 12, D-24105 Kiel, Germany

 Vilnius Univ, Inst Biotechnol, Vilnius, Lithuania

Aliberti, S:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

 Univ Milan, Milan, Italy

Monzani, V:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

Moreno, V:
 Consortium Biomed Res Epidemiol & Publ Hlth, Catalan Inst Oncol, Bellvitge Biomed Res Inst, Barcelona, Spain

 Univ Barcelona, Barcelona, Spain

Wesse, T:
 Univ Kiel, Inst Clin Mol Biol, Rosalind Franklin Str 12, D-24105 Kiel, Germany

Lenz, TL:
 Max Planck Inst Evolutionary Biol, Res Grp Evolutionary Immunogen, Plon, Germany

Pumarola, T:
 Autonomous Univ Barcelona, Univ Hosp Vall dHebron, Immunohematol Dept, Dept Microbiol,Banc Sang & Teixits, Barcelona, Spain

 Autonoma Univ Barcelona, Barcelona, Spain

Rimoldi, V:
 Humanitas Univ, Dept Biomed Sci, Milan, Italy

Bosari, S:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

 Univ Milan, Milan, Italy

Albrecht, W:
 Univ Kiel, Inst Clin Mol Biol, Rosalind Franklin Str 12, D-24105 Kiel, Germany

Peter, W:
 Stefan Morsch Stiftung, Birkenfeld, Germany

Romero-Gomez, M:
 Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain

 Univ Seville, Virgen Rocio Univ Hosp, Inst Biomed Seville, Digest Dis Unit, Seville, Spain

D'Amato, M:
 Univ Kiel, Inst Clin Mol Biol, Rosalind Franklin Str 12, D-24105 Kiel, Germany

 Biodonostia Hlth Res Inst, Dept Liver & Gastrointestinal Dis, San Sebastian, Spain

 Basque Fdn Sci, IKERBASQUE, Bilbao, Spain

 Monash Univ, Sch Biol Sci, Clayton, Vic, Australia

 Karolinska Inst, Dept Med Solna, Unit Clin Epidemiol, Stockholm, Sweden

Duga, S:
 Humanitas Univ, Dept Biomed Sci, Milan, Italy

 IRCCS, Humanitas Clin & Res Ctr, Milan, Italy

Banales, JM:
 Univ Basque Country, Dept Liver & Gastrointestinal Dis, Biodonostia Hlth Res Inst, Donostia Univ Hospital, San Sebastian, Spain

 Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain

 Basque Fdn Sci, IKERBASQUE, Bilbao, Spain

Hov, JR:
 Oslo Univ Hosp, Div Surg Inflammatory Dis & Transplantat, Dept Transplantat Med, Rikshospitalet,Norwegian PSC Res Ctr, Oslo, Norway

 Oslo Univ Hosp, Internal Med Res Inst, Div Surg Inflammatory Dis & Transplantat, Rikshospitalet, Oslo, Norway

 Univ Oslo, Postboks 4950 Nydalen, N-0424 Oslo, Norway

 Oslo Univ Hosp, Div Canc Med Surg & Transplantat, Sect Gastroenterol, Dept Transplantat Med,Rikshospitalet, Oslo, Norway

Folseraas, T:
 Oslo Univ Hosp, Div Surg Inflammatory Dis & Transplantat, Dept Transplantat Med, Rikshospitalet,Norwegian PSC Res Ctr, Oslo, Norway

 Oslo Univ Hosp, Internal Med Res Inst, Div Surg Inflammatory Dis & Transplantat, Rikshospitalet, Oslo, Norway

 Univ Oslo, Postboks 4950 Nydalen, N-0424 Oslo, Norway

 Oslo Univ Hosp, Div Canc Med Surg & Transplantat, Sect Gastroenterol, Dept Transplantat Med,Rikshospitalet, Oslo, Norway

Valenti, L:
 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

 Univ Milan, Milan, Italy

Franke, A:
 Univ Kiel, Inst Clin Mol Biol, Rosalind Franklin Str 12, D-24105 Kiel, Germany

 Univ Hosp Schleswig Holstein, Campus Kiel, Kiel, Germany

Karlsen, TH:
 Oslo Univ Hosp, Div Surg Inflammatory Dis & Transplantat, Dept Transplantat Med, Rikshospitalet,Norwegian PSC Res Ctr, Oslo, Norway

 Oslo Univ Hosp, Internal Med Res Inst, Div Surg Inflammatory Dis & Transplantat, Rikshospitalet, Oslo, Norway

 Univ Oslo, Postboks 4950 Nydalen, N-0424 Oslo, Norway

 Oslo Univ Hosp, Div Canc Med Surg & Transplantat, Sect Gastroenterol, Dept Transplantat Med,Rikshospitalet, Oslo, Norway
ISSN: 00284793





New England Journal of Medicine
Editorial
Massachusetts Medical Society, WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA, Estados Unidos America
Tipo de documento: Article
Volumen: 383 Número: 16
Páginas: 1522-1534
WOS Id: 000580486200009
ID de PubMed: 32558485
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