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1. Gene therapy-emulating small molecule treatments in cystic fibrosis airway epithelial cells and patients

Author: Yang, Q., Soltis, A. R., Sukumar, G., Zhang, X., Caohuy, H., Freedy, J., Dalgard, C. L., Wilkerson, M. D., Pollard, H. B., and Pollard, B. S.
Published: 2019
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2. ImmunoTyper-SR: A Novel Computational Approach for Genotyping Immunoglobulin Heavy Chain Variable Genes Using Short Read Data

Author: Ford M., Hari A., Rodriguez O., Xu J., Lack J., Oguz C., Zhang Y., Weber S., Magliocco M., Barnett J., Xirasagar S., Samuel S., Imberti L., Bonfanti P., Biondi A., Dalgard C. L., Chanock S., Rosen L., Holland S., Su H., Notarangelo L., Vishkin U., Watson C., Sahinalp S. C., Pe'er, I, Ford, M, Hari, A, Rodriguez, O, Xu, J, Lack, J, Oguz, C, Zhang, Y, Weber, S, Magliocco, M, Barnett, J, Xirasagar, S, Samuel, S, Imberti, L, Bonfanti, P, Biondi, A, Dalgard, C, Chanock, S, Rosen, L, Holland, S, Su, H, Notarangelo, L, Vishkin, U, Watson, C, and Sahinalp, S
Subjects: Molecular Biology
Abstract: The human immunoglobulin heavy chain (IGH) locus on chromosome 14 includes more than 40 functional copies of the variable gene (IGHV).
Published: 2022

3. Dietary Modulation of Paraoxonase-1 Activity and Concentration in Humans

Author: Dalgård, C., Ridley, Anne, editor, Frampton, Jon, editor, Mackness, Bharti, editor, Mackness, Mike, editor, Aviram, Michael, editor, and Paragh, György, editor
Published: 2008
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4. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Author: Zhang Q., Liu Z., Moncada-Velez M., Chen J., Ogishi M., Bigio B., Yang R., Arias A. A., Zhou Q., Han J. E., Ugurbil A. C., Zhang P., Rapaport F., Li J., Spaan A. N., Boisson B., Boisson-Dupuis S., Bustamante J., Puel A., Ciancanelli M. J., Zhang S. -Y., Beziat V., Jouanguy E., Abel L., Cobat A., Casanova J. -L., Bastard P., Korol C., Rosain J., Philippot Q., Chbihi M., Lorenzo L., Bizien L., Neehus A. -L., Kerner G., Seeleuthner Y., Manry J., Le Voyer T., Le Pen J., Schneider W. M., Razooky B. S., Hoffmann H. -H., Michailidis E., Rice C. M., Sabli I. K. D., Hodeib S., Sancho-Shimizu V., Bilguvar K., Ye J., Maniatis T., Bolze A., Zhang Y., Notarangelo L. D., Su H. C., Onodi F., Korniotis S., Karpf L., Soumelis V., Bonnet-Madin L., Amara A., Dorgham K., Gorochov G., Smith N., Duffy D., Moens L., Meyts I., Meade P., Garcia-Sastre A., Krammer F., Corneau A., Masson C., Schmitt Y., Schluter A., Pujol A., Khan T., Marr N., Fellay J., Roussel L., Vinh D. C., Shahrooei M., Alosaimi M. F., Alsohime F., Hasanato R., Mansouri D., Al-Saud H., Almourfi F., Al-Mulla F., Al-Muhsen S. Z., Al Turki S., van de Beek D., Biondi A., Bettini L. R., D'Angio M., Bonfanti P., Imberti L., Sottini A., Paghera S., Quiros-Roldan E., Rossi C., Oler A. J., Tompkins M. F., Alba C., Dalgard C. L., Vandernoot I., Smits G., Goffard J. -C., Migeotte I., Haerynck F., Soler-Palacin P., Martin-Nalda A., Colobran R., Morange P. -E., Keles S., Colkesen F., Ozcelik T., Yasar K. K., Senoglu S., Karabela S. N., Rodriguez-Gallego C., Novelli G., Hraiech S., Tandjaoui-Lambiotte Y., Duval X., Laouenan C., Snow A. L., Milner J. D., Mogensen T. H., Nussenzweig M., Lifton R. P., Foti G., Bellani G., Citerio G., Contro E., Pesci A., Valsecchi M. G., Cazzaniga M., Abad J., Blanco I., Rodrigo C., Aguilera-Albesa S., Akcan O. M., Darazam I. A., Aldave J. C., Ramos M. A., Nadji S. A., Alkan G., Allardet-Servent J., Allende L. M., Alsina L., Alyanakian M. -A., Amador-Borrero B., Mouly S., Sene D., Amoura Z., Mathian A., Antoli A., Blanch G. R., Riera J. S., Moreno X. S., Arslan S., Assant S., Auguet T., Azot A., Bajolle F., Levy R., Oualha M., Baldolli A., Ballester M., Feldman H. B., Barrou B., Beurton A., Bilbao A., Blanchard-Rohner G., Blandinieres A., Rivet N., Blazquez-Gamero D., Bloomfield M., Bolivar-Prados M., Clave P., Borie R., Bosteels C., Lambrecht B. N., van Braeckel E., Bousfiha A. A., Bouvattier C., Vincent A., Boyarchuk O., Bueno M. R. P., Castro M. V., Matos L. R. B., Zatz M., Agra J. J. C., Calimli S., Capra R., Carrabba M., Fabio G., Casasnovas C., Velez-Santamaria V., Caseris M., Falck A., Poncelet G., Castelle M., Castelli F., de Vera M. C., Catherinot E., Chalumeau M., Toubiana J., Charbit B., Li Z., Pellegrini S., Cheng M. P., Clotet B., Codina A., Comarmond C., Dalmau D., Darley D. R., Dauby N., Dauger S., Le Bourgeois F., Levy M., de Pontual L., Dehban A., Delplancq G., Demoule A., Diehl J. -L., Dobbelaere S., Durand S., Mircher C., Rebillat A. -S., Vilaire M. E., Eldars W., Elgamal M., Elnagdy M. H., Emiroglu M., Erdeniz E. H., Aytekin S. E., Euvrard R., Evcen R., Faivre L., Fartoukh M., Faure M., Arquero M. F., Flores C., Francois B., Fumado V., Fusco F., Ursini M. V., Solis B. G., de Diego R. P., van Den Rym A. M., Gaussem P., Gil-Herrera J., Gilardin L., Alarcon M. G., Girona-Alarcon M., Gok F., Yosunkaya A., Gonzalez-Montelongo R., Inigo-Campos A., Lorenzo-Salazar J. M., Munoz-Barrera A., Guerder A., Gul Y., Guner S. N., Gut M., Hadjadj J., Halwani R., Hammarstrom L., Hatipoglu N., Hernandez-Brito E., Heijmans C., Holanda-Pena M. S., Horcajada J. P., Hoste L., Hoste E., Humbert L., Mordacq C., Thumerelle C., Vuotto F., Iglesias A. D., Jamme M., Arranz M. J., Jordan I., Jorens P., Kanat F., Kapakli H., Kara I., Karbuz A., Demirkol Y. K., Klocperk A., Krol Z. J., Kuentz P., Kwan Y. W. M., Lagier J. -C., Lau Y. -L., Leung D., Leo Y. -S., Young B. E., Lopez R. L., Levin M., Linglart A., Loeys B., Louapre C., Lubetzki C., Luyt C. -E., Lye D. C., Marjani M., Pereira J. M., Martin A., Pueyo D. M., Martinez-Picado J., Marzana I., Matthews G. V., Mayaux J., Parizot C., Quentric P., Mege J. -L., Raoult D., Melki I., Meritet J. -F., Metin O., Mezidi M., Taccone F., Millereux M., Mirault T., Mirsaeidi M., Melian A. M., Martinez A. M., Morange P., Morelle G., Naesens L., Nafati C., Neves J. F., Ng L. F. P., Medina Y. N., Cuadros E. N., Gonzalo Ocejo-Vinyals J., Orbak Z., Pan-Hammarstrom Q., Pascreau T., Paz-Artal E., Philippe A., Planas-Serra L., Ploin D., Viel S., Poissy J., Pouletty M., Reisli I., Ricart P., Richard J. -C., Riviere J. G., Rodriguez-Palmero A., Romero C. S., Rothenbuhler A., Rozenberg F., del Prado M. Y. R., Sanchez O., Sanchez-Ramon S., Schmidt M., Schweitzer C. E., Scolari F., Sediva A., Seijo L. M., Seppanen M. R. J., Ilovich A. S., Slabbynck H., Smadja D. M., Sobh A., Sole-Violan J., Soler C., Stepanovskiy Y., Stoclin A., Taupin J. -L., Tavernier S. J., Terrier B., Tomasoni G., Alvarez J. T., Trouillet-Assant S., Troya J., Tucci A., Uzunhan Y., Vabres P., Valencia-Ramos J., van de Velde S., van Praet J., Vatansev H., Vilain C., Voiriot G., Yucel F., Zannad F., Belot A., Bole-Feysot C., Lyonnet S., Nitschke P., Pouliet A., Tores F., Zarhrate M., Andrejak C., Angoulvant F., Bachelet D., Bhavsar K., Bouadma L., Chair A., Couffignal C., Silveira C. D., Debray M. -P., Eloy P., Esposito-Farese M., Ettalhaoui N., Gault N., Ghosn J., Gorenne I., Hoffmann I., Kafif O., Kali S., Khalil A., Laribi S., Le M., Le Hingrat Q., Lescure F. -X., Lucet J. C., Mentre F., Mullaert J., Peiffer-Smadja N., Peytavin G., Roy C., Schneider M., Mohammed N. S., Tagherset L., Tardivon C., Tellier M. -C., Timsit J. -F., Trioux T., Tubiana S., Basmaci R., Behillil S., Beluze M., Benkerrou D., Dorival C., Meziane A., Teoule F., Bompart F., Bouscambert M., Gaymard A., Lina B., Rosa-Calatrava M., Terrier O., Caralp M., Cervantes-Gonzalez M., D'Ortenzio E., Puechal O., Semaille C., Coelho A., Diouf A., Hoctin A., Mambert M., Couffin-Cadiergues S., Deplanque D., Descamps D., Visseaux B., Desvallees M., Khan C., Diallo A., Mercier N., Paul C., Petrov-Sanchez V., Dubos F., Enouf V. V. E., Mouquet H., Esperou H., Jaafoura S., Papadopoulos A., Etienne M., Gigante T., Rossignol B., Guedj J., Le Nagard H., Lingas G., Neant N., Kaguelidou F., Levy Y., Wiedemann A., Levy-Marchal C., Malvy D., Noret M., Pages J., Picone O., Rossignol P., Tual C., Veislinger A., van der Werf S., Vanel N., Yazdanpanah Y., Alavoine L., Costa Y., Ecobichon J. -L., Frezouls W., Ilic-Habensus E., Leclercq A., Lehacaut J., Letrou S., Mandic M., Nouroudine M., Quintin C., Rexach J., Vignali V., Amat K. K. A., Enouf V., Bielicki J., Bruijning P., Burdet C., Caumes E., Charpentier C., Damond F., Coignard B., Delmas C., Roufai L., Dechanet A., Houhou N., Kikoine J., Manchon P., Piquard V., Postolache A., Terzian Z., Lebeaux D., Lucet J. -C., Meghadecha M., Motiejunaite J., Thy M., van Agtmael M., Bomers M., Chouchane O., Geerlings S., Goorhuis B., Grobusch M. P., Harris V., Hermans S. M., Hovius J. W., Nellen J., Peters E., van der Poll T., Prins J. M., Reijnders T., Schinkel M., Sigaloff K., Stijnis C. S., van der Valk M., van Vugt M., Joost Wiersinga W., Algera A. G., van Baarle F., Bos L., Botta M., de Bruin S., Bulle E., Elbers P., Fleuren L., Girbes A., Hagens L., Heunks L., Horn J., van Mourik N., Paulus F., Raasveld J., Schultz M. J., Smit M., Stilma W., Thoral P., Tsonas A., de Vries H., Bax D., Cloherty A., Beudel M., Brouwer M. C., Koning R., Bogaard H. J., de Brabander J., de Bree G., Bugiani M., Geerts B., Hollmann M. W., Preckel B., Veelo D., Geijtenbeek T., Hafkamp F., Hamann J., Hemke R., de Jong M. D., Schuurman A., Teunissen C., Vlaar A. P. J., Wouters D., Zwinderman A. H., Aiuti A., Muhsen S. A., Anderson M. S., Bogunovic D., Itan Y., Cirulli E., Barrett K. S., Washington N., Bondarenko A., Brodin P., Bryceson Y., Bustamante C. D., Butte M., Casari G., Chakravorty S., Christodoulou J., Le Mestre S., Condino-Neto A., Cooper M. A., David A., DeRisi J. L., Desai M., Drolet B. A., Espinosa S., Franco J. L., Gregersen P. K., Hagin D., Heath J., Henrickson S. E., Hsieh E., Imai K., Karamitros T., Kisand K., Ku C. -L., Ling Y., Lucas C. L., Marodi L., Milner J., Mironska K., Mogensen T., Morio T., Novelli A., O'Farrelly C., Okada S., Planas A. M., Prando C., Quintana-Murci L., Renia L., Renieri A., Sankaran V., Snow A., Tangye S., Turvey S., Uddin F., Uddin M. J., Vazquez S. E., von Bernuth H., Zawadzki P., Jing H., Tung W., Meguro K., Shaw E., Shafer S., Zheng L., Zhang Z., Kubo S., Chauvin S. D., Lenardo M., Luthers C. R., Bauman B. M., Lack J., Karlins E., Hupalo D. M., Rosenberger J., Sukumar G., Wilkerson M. D., Zhang X., Rockefeller University [New York], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris], Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cytométrie Pitié-Salpêtrière (PASS-CYPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), R01AI088364, National Institutes of Health, Howard Hughes Medical Institute, UL1 TR001866, NIH Clinical and Translational Science Award, fast grant, Emergent Ventures, St. Giles Foundation, National Center for Advancing Translational Sciences, Rockefeller University, ANR-10-IAHU-01, Agence Nationale de la Recherche, UM1HG006504 and U24HG008956, National Human Genome Research Institute, ANR-10-LABX-62-IBEID, the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence, EQU201903007798, the French Foundation for Medical Research, Özçelik, Tayfun, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut Pasteur [Paris] (IP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Virologie (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-17-CE15-0003,DENDRISEPSIS,Analyse systémique des cellules présentatrices d'antigène dans le sepsis humain(2017), ANR-20-COVI-0025,iCovid,Immunopathologie du COVID-19 à l'Assistance Publique Hôpitaux de Paris(2020), Zhang, Qian, Bastard, Paul, Le Pen, Jeremie, Moncada-Velez, Marcela, Ogishi, Masato, Sabli, Ira K. D., Hodeib, Stephanie, Korol, Cecilia, Bilguvar, Kaya, Bolze, Alexandre, Bigio, Benedetta, Yang, Rui, Arias, Andrés Augusto, Zhou, Qinhua, Chbihi, Marwa, Bonnet-Madin, Lucie, Dorgham, Karim, Smith, Nikaïa, Schneider, William M., Razooky, Brandon S., Hoffmann, Hans-Heinrich, Michailidis, Eleftherios, Han, Jin Eun, Lorenzo, Lazaro, Bizien, Lucy, Meade, Philip, Neehus, Anna-Lena, Ugurbil, Aileen Camille, Kerner, Gaspard, Zhang, Peng, Rapaport, Franck, Manry, Jérémy, Masson, Cecile, Schlüter, Agatha, Le Voyer, Tom, Khan, Taushif, Fellay, Jacques, Roussel, Lucie, Alosaimi, Mohammed F., Al-Mulla, Fahd, Almourfi, Feras, Alsohime, Fahad, Al Turki, Saeed, Hasanato, Rana, Beek, Diederik van der, Bettini, Laura Rachele, Bonfanti, Paolo, Oler, Andrew J., Tompkins, Miranda F., Alba, Camille, Smits, Guillaume, Soler-Palacín, Pere, Martin-Nalda, Andrea, Colobran, Roger, Çölkesen, Fatma, Yasar, Kadriye Kart, Senoglu, Sevtap, Karabela, Şemsi Nur, Rodríguez-Gallego, Carlos, Novelli, Giuseppe, Tandjaoui-Lambiotte, Yacine, Laouénan, Cédric, Zhang, Q, Bastard, P, Liu, Z, Le Pen, J, Moncada-Velez, M, Chen, J, Ogishi, M, Sabli, I, Hodeib, S, Korol, C, Rosain, J, Bilguvar, K, Ye, J, Bolze, A, Bigio, B, Yang, R, Arias, A, Zhou, Q, Zhang, Y, Onodi, F, Korniotis, S, Karpf, L, Philippot, Q, Chbihi, M, Bonnet-Madin, L, Dorgham, K, Smith, N, Schneider, W, Razooky, B, Hoffmann, H, Michailidis, E, Moens, L, Han, J, Lorenzo, L, Bizien, L, Meade, P, Neehus, A, Ugurbil, A, Corneau, A, Kerner, G, Zhang, P, Rapaport, F, Seeleuthner, Y, Manry, J, Masson, C, Schmitt, Y, Schlüter, A, Le Voyer, T, Khan, T, Li, J, Fellay, J, Roussel, L, Shahrooei, M, Alosaimi, M, Mansouri, D, Al-Saud, H, Al-Mulla, F, Almourfi, F, Al-Muhsen, S, Alsohime, F, Al Turki, S, Hasanato, R, van de Beek, D, Biondi, A, Bettini, L, D'Angio, M, Bonfanti, P, Imberti, L, Sottini, A, Paghera, S, Quiros-Roldan, E, Rossi, C, Oler, A, Tompkins, M, Alba, C, Vandernoot, I, Goffard, J, Smits, G, Migeotte, I, Haerynck, F, Soler-Palacin, P, Martin-Nalda, A, Colobran, R, Morange, P, Keles, S, Çölkesen, F, Ozcelik, T, Yasar, K, Senoglu, S, Karabela, Ş, Gallego, C, Novelli, G, Hraiech, S, Tandjaoui-Lambiotte, Y, Duval, X, Laouénan, C, Snow, A, Dalgard, C, Milner, J, Vinh, D, Mogensen, T, Marr, N, Spaan, A, Boisson, B, Boisson-Dupuis, S, Bustamante, J, Puel, A, Ciancanelli, M, Meyts, I, Maniatis, T, Soumelis, V, Amara, A, Nussenzweig, M, García-Sastre, A, Krammer, F, Pujol, A, Duffy, D, Lifton, R, Zhang, S, Gorochov, G, Béziat, V, Jouanguy, E, Sancho-Shimizu, V, Rice, C, Abel, L, Notarangelo, L, Cobat, A, Su, H, Casanova, J, Pesci, A, Neurology, AII - Infectious diseases, ANS - Neuroinfection & -inflammation, Infectious diseases, ACS - Pulmonary hypertension & thrombosis, Intensive Care Medicine, ACS - Heart failure & arrhythmias, Anesthesiology, ACS - Diabetes & metabolism, ACS - Microcirculation, UKRI Future Leader's Fellowship, Internal medicine, Pulmonary medicine, Intensive care medicine, Pathology, Medical Microbiology and Infection Prevention, Amsterdam Reproduction & Development (AR&D), Amsterdam Neuroscience - Neuroinfection & -inflammation, Laboratory Medicine, APH - Quality of Care, COVID-STORM Clinicians, COVID Clinicians, Imagine COVID Group, French COVID Cohort Study Group, CoV-Contact Cohort, Amsterdam UMC Covid-19 Biobank, COVID Human Genetic Effort, NIAID-USUHS/TAGC COVID Immunity Group, Foti, G., Bellani, G., Citerio, G., Contro, E., Pesci, A., Valsecchi, M.G., Cazzaniga, M., Abad, J., Aguilera-Albesa, S., Akcan, O.M., Darazam, I.A., Aldave, J.C., Ramos, M.A., Nadji, S.A., Alkan, G., Allardet-Servent, J., Allende, L.M., Alsina, L., Alyanakian, M.A., Amador-Borrero, B., Amoura, Z., Antolí, A., Arslan, S., Assant, S., Auguet, T., Azot, A., Bajolle, F., Baldolli, A., Ballester, M., Feldman, H.B., Barrou, B., Beurton, A., Bilbao, A., Blanchard-Rohner, G., Blanco, I., Blandinières, A., Blazquez-Gamero, D., Bloomfield, M., Bolivar-Prados, M., Borie, R., Bosteels, C., Bousfiha, A.A., Bouvattier, C., Boyarchuk, O., Bueno, MRP, Bustamante, J., Cáceres Agra, J.J., Calimli, S., Capra, R., Carrabba, M., Casasnovas, C., Caseris, M., Castelle, M., Castelli, F., de Vera, M.C., Castro, M.V., Catherinot, E., Chalumeau, M., Charbit, B., Cheng, M.P., Clavé, P., Clotet, B., Codina, A., Colkesen, F., Çölkesen, F., Colobran, R., Comarmond, C., Dalmau, D., Darley, D.R., Dauby, N., Dauger, S., de Pontual, L., Dehban, A., Delplancq, G., Demoule, A., Diehl, J.L., Dobbelaere, S., Durand, S., Eldars, W., Elgamal, M., Elnagdy, M.H., Emiroglu, M., Erdeniz, E.H., Aytekin, S.E., Euvrard, R., Evcen, R., Fabio, G., Faivre, L., Falck, A., Fartoukh, M., Faure, M., Arquero, M.F., Flores, C., Francois, B., Fumadó, V., Fusco, F., Solis, B.G., Gaussem, P., Gil-Herrera, J., Gilardin, L., Alarcon, M.G., Girona-Alarcón, M., Goffard, J.C., Gok, F., González-Montelongo, R., Guerder, A., Gul, Y., Guner, S.N., Gut, M., Hadjadj, J., Haerynck, F., Halwani, R., Hammarström, L., Hatipoglu, N., Hernandez-Brito, E., Heijmans, C., Holanda-Peña, M.S., Horcajada, J.P., Hoste, L., Hoste, E., Hraiech, S., Humbert, L., Iglesias, A.D., Íñigo-Campos, A., Jamme, M., Arranz, M.J., Jordan, I., Jorens, P., Kanat, F., Kapakli, H., Kara, I., Karbuz, A., Yasar, K.K., Keles, S., Demirkol, Y.K., Klocperk, A., Król, Z.J., Kuentz, P., Kwan, YWM, Lagier, J.C., Lambrecht, B.N., Lau, Y.L., Le Bourgeois, F., Leo, Y.S., Lopez, R.L., Leung, D., Levin, M., Levy, M., Lévy, R., Li, Z., Linglart, A., Loeys, B., Lorenzo-Salazar, J.M., Louapre, C., Lubetzki, C., Luyt, C.E., Lye, D.C., Mansouri, D., Marjani, M., Pereira, J.M., Martin, A., Pueyo, D.M., Martinez-Picado, J., Marzana, I., Mathian, A., Matos, LRB, Matthews, G.V., Mayaux, J., Mège, J.L., Melki, I., Meritet, J.F., Metin, O., Meyts, I., Mezidi, M., Migeotte, I., Millereux, M., Mirault, T., Mircher, C., Mirsaeidi, M., Melián, A.M., Martinez, A.M., Morange, P., Mordacq, C., Morelle, G., Mouly, S., Muñoz-Barrera, A., Naesens, L., Nafati, C., Neves, J.F., Ng, LFP, Medina, Y.N., Cuadros, E.N., Ocejo-Vinyals, J.G., Orbak, Z., Oualha, M., Özçelik, T., Pan-Hammarström, Q., Parizot, C., Pascreau, T., Paz-Artal, E., Pellegrini, S., de Diego, R.P., Philippe, A., Philippot, Q., Planas-Serra, L., Ploin, D., Poissy, J., Poncelet, G., Pouletty, M., Quentric, P., Raoult, D., Rebillat, A.S., Reisli, I., Ricart, P., Richard, J.C., Rivet, N., Rivière, J.G., Blanch, G.R., Rodrigo, C., Rodriguez-Gallego, C., Rodríguez-Palmero, A., Romero, C.S., Rothenbuhler, A., Rozenberg, F., Ruiz Del Prado, M.Y., Riera, J.S., Sanchez, O., Sánchez-Ramón, S., Schluter, A., Schmidt, M., Schweitzer, C.E., Scolari, F., Sediva, A., Seijo, L.M., Sene, D., Senoglu, S., Seppänen, MRJ, Ilovich, A.S., Shahrooei, M., Slabbynck, H., Smadja, D.M., Sobh, A., Moreno, X.S., Solé-Violán, J., Soler, C., Soler-Palacín, P., Stepanovskiy, Y., Stoclin, A., Taccone, F., Tandjaoui-Lambiotte, Y., Taupin, J.L., Tavernier, S.J., Terrier, B., Thumerelle, C., Tomasoni, G., Toubiana, J., Alvarez, J.T., Trouillet-Assant, S., Troya, J., Tucci, A., Ursini, M.V., Uzunhan, Y., Vabres, P., Valencia-Ramos, J., Van Braeckel, E., Van de Velde, S., Van Den Rym, A.M., Van Praet, J., Vandernoot, I., Vatansev, H., Vélez-Santamaria, V., Viel, S., Vilain, C., Vilaire, M.E., Vincent, A., Voiriot, G., Vuotto, F., Yosunkaya, A., Young, B.E., Yucel, F., Zannad, F., Zatz, M., Belot, A., Bole-Feysot, C., Lyonnet, S., Masson, C., Nitschke, P., Pouliet, A., Schmitt, Y., Tores, F., Zarhrate, M., Abel, L., Andrejak, C., Angoulvant, F., Bachelet, D., Basmaci, R., Behillil, S., Beluze, M., Benkerrou, D., Bhavsar, K., Bompart, F., Bouadma, L., Bouscambert, M., Caralp, M., Cervantes-Gonzalez, M., Chair, A., Coelho, A., Couffignal, C., Couffin-Cadiergues, S., D'Ortenzio, E., Da Silveira, C., Debray, M.P., Deplanque, D., Descamps, D., Desvallées, M., Diallo, A., Diouf, A., Dorival, C., Dubos, F., Duval, X., Eloy, P., Enouf, V.V., Esperou, H., Esposito-Farese, M., Etienne, M., Ettalhaoui, N., Gault, N., Gaymard, A., Ghosn, J., Gigante, T., Gorenne, I., Guedj, J., Hoctin, A., Hoffmann, I., Jaafoura, S., Kafif, O., Kaguelidou, F., Kali, S., Khalil, A., Khan, C., Laouénan, C., Laribi, S., Le, M., Le Hingrat, Q., Le Mestre, S., Le Nagard, H., Lescure, F.X., Lévy, Y., Levy-Marchal, C., Lina, B., Lingas, G., Lucet, J.C., Malvy, D., Mambert, M., Mentré, F., Mercier, N., Meziane, A., Mouquet, H., Mullaert, J., Neant, N., Noret, M., Pages, J., Papadopoulos, A., Paul, C., Peiffer-Smadja, N., Petrov-Sanchez, V., Peytavin, G., Picone, O., Puéchal, O., Rosa-Calatrava, M., Rossignol, B., Rossignol, P., Roy, C., Schneider, M., Semaille, C., Mohammed, N.S., Tagherset, L., Tardivon, C., Tellier, M.C., Téoulé, F., Terrier, O., Timsit, J.F., Trioux, T., Tual, C., Tubiana, S., van der Werf, S., Vanel, N., Veislinger, A., Visseaux, B., Wiedemann, A., Yazdanpanah, Y., Alavoine, L., Amat, KKA, Bielicki, J., Bruijning, P., Burdet, C., Caumes, E., Charpentier, C., Coignard, B., Costa, Y., Damond, F., Dechanet, A., Delmas, C., Ecobichon, J.L., Enouf, V., Espérou, H., Frezouls, W., Houhou, N., Ilic-Habensus, E., Kikoine, J., Lebeaux, D., Leclercq, A., Lehacaut, J., Letrou, S., Manchon, P., Mandic, M., Meghadecha, M., Motiejunaite, J., Nouroudine, M., Piquard, V., Postolache, A., Quintin, C., Rexach, J., Roufai, L., Terzian, Z., Thy, M., Vignali, V., van Agtmael, M., Algera, A.G., van Baarle, F., Bax, D., Beudel, M., Bogaard, H.J., Bomers, M., Bos, L., Botta, M., de Brabander, J., de Bree, G., Brouwer, M.C., de Bruin, S., Bugiani, M., Bulle, E., Chouchane, O., Cloherty, A., Elbers, P., Fleuren, L., Geerlings, S., Geerts, B., Geijtenbeek, T., Girbes, A., Goorhuis, B., Grobusch, M.P., Hafkamp, F., Hagens, L., Hamann, J., Harris, V., Hemke, R., Hermans, S.M., Heunks, L., Hollmann, M.W., Horn, J., Hovius, J.W., de Jong, M.D., Koning, R., van Mourik, N., Nellen, J., Paulus, F., Peters, E., van der Poll, T., Preckel, B., Prins, J.M., Raasveld, J., Reijnders, T., Schinkel, M., Schultz, M.J., Schuurman, A., Sigaloff, K., Smit, M., Stijnis, C.S., Stilma, W., Teunissen, C., Thoral, P., Tsonas, A., van der Valk, M., Veelo, D., Vlaar, APJ, de Vries, H., van Vugt, M., Wiersinga, W.J., Wouters, D., Zwinderman, AHK, van de Beek, D., Aiuti, A., Al Muhsen, S., Al-Mulla, F., Anderson, M.S., Arias, A.A., Bogunovic, D., Bolze, A., Bondarenko, A., Brodin, P., Bryceson, Y., Bustamante, C.D., Butte, M., Casari, G., Chakravorty, S., Christodoulou, J., Cirulli, E., Condino-Neto, A., Cooper, M.A., Dalgard, C.L., David, A., DeRisi, J.L., Desai, M., Drolet, B.A., Espinosa, S., Fellay, J., Franco, J.L., Gregersen, P.K., Hagin, D., Heath, J., Henrickson, S.E., Hsieh, E., Imai, K., Itan, Y., Karamitros, T., Kisand, K., Ku, C.L., Ling, Y., Lucas, C.L., Maniatis, T., Marodi, L., Milner, J., Mironska, K., Mogensen, T., Morio, T., Notarangelo, L.D., Novelli, A., Novelli, G., O'Farrelly, C., Okada, S., Ozcelik, T., Planas, A.M., Prando, C., Pujol, A., Quintana-Murci, L., Renia, L., Renieri, A., Rodríguez-Gallego, C., Sancho-Shimizu, V., Sankaran, V., Barrett, K.S., Snow, A., Spaan, A.N., Tangye, S., Turvey, S., Uddin, F., Uddin, M.J., Vazquez, S.E., Vinh, D.C., von Bernuth, H., Washington, N., Zawadzki, P., Su, H.C., Casanova, J.L., Jing, H., Tung, W., Luthers, C.R., Bauman, B.M., Shafer, S., Zheng, L., Zhang, Z., Kubo, S., Chauvin, S.D., Meguro, K., Shaw, E., Lenardo, M., Lack, J., Karlins, E., Hupalo, D.M., Rosenberger, J., Sukumar, G., Wilkerson, M.D., Zhang, X., Children's Hospital, HUS Children and Adolescents, Clinicum, Department of Medicine, Zhang, Q., Liu, Z., Moncada-Velez, M., Chen, J., Ogishi, M., Bigio, B., Yang, R., Arias, A. A., Zhou, Q., Han, J. E., Ugurbil, A. C., Zhang, P., Rapaport, F., Li, J., Spaan, A. N., Boisson, B., Boisson-Dupuis, S., Puel, A., Ciancanelli, M. J., Zhang, S. -Y., Beziat, V., Jouanguy, E., Cobat, A., Casanova, J. -L., Bastard, P., Korol, C., Rosain, J., Chbihi, M., Lorenzo, L., Bizien, L., Neehus, A. -L., Kerner, G., Seeleuthner, Y., Manry, J., Le Voyer, T., Le Pen, J., Schneider, W. M., Razooky, B. S., Hoffmann, H. -H., Michailidis, E., Rice, C. M., Sabli, I. K. D., Hodeib, S., Bilguvar, K., Ye, J., Zhang, Y., Notarangelo, L. D., Su, H. C., Onodi, F., Korniotis, S., Karpf, L., Soumelis, V., Bonnet-Madin, L., Amara, A., Dorgham, K., Gorochov, G., Smith, N., Duffy, D., Moens, L., Meade, P., Garcia-Sastre, A., Krammer, F., Corneau, A., Khan, T., Marr, N., Roussel, L., Vinh, D. C., Alosaimi, M. F., Alsohime, F., Hasanato, R., Al-Saud, H., Almourfi, F., Al-Muhsen, S. Z., Al Turki, S., Biondi, A., Bettini, L. R., D'Angio, M., Bonfanti, P., Imberti, L., Sottini, A., Paghera, S., Quiros-Roldan, E., Rossi, C., Oler, A. J., Tompkins, M. F., Alba, C., Dalgard, C. L., Smits, G., Goffard, J. -C., Soler-Palacin, P., Martin-Nalda, A., Morange, P. -E., Yasar, K. K., Karabela, S. N., Laouenan, C., Snow, A. L., Milner, J. D., Mogensen, T. H., Nussenzweig, M., Lifton, R. P., Valsecchi, M. G., Akcan, O. M., Darazam, I. A., Aldave, J. C., Ramos, M. A., Nadji, S. A., Allende, L. M., Alyanakian, M. -A., Antoli, A., Blanch, G. R., Riera, J. S., Moreno, X. S., Levy, R., Feldman, H. B., Blandinieres, A., Clave, P., Lambrecht, B. N., van Braeckel, E., Bousfiha, A. A., Bueno, M. R. P., Castro, M. V., Matos, L. R. B., Agra, J. J. C., Velez-Santamaria, V., de Vera, M. C., Cheng, M. P., Darley, D. R., Diehl, J. -L., Rebillat, A. -S., Vilaire, M. E., Elnagdy, M. H., Erdeniz, E. H., Aytekin, S. E., Arquero, M. F., Fumado, V., Ursini, M. V., Solis, B. G., de Diego, R. P., van Den Rym, A. M., Alarcon, M. G., Girona-Alarcon, M., Gonzalez-Montelongo, R., Inigo-Campos, A., Lorenzo-Salazar, J. M., Munoz-Barrera, A., Guner, S. N., Hammarstrom, L., Holanda-Pena, M. S., Horcajada, J. P., Iglesias, A. D., Arranz, M. J., Demirkol, Y. K., Krol, Z. J., Kwan, Y. W. M., Lagier, J. -C., Lau, Y. -L., Leo, Y. -S., Young, B. E., Lopez, R. L., Luyt, C. -E., Lye, D. C., Pereira, J. M., Pueyo, D. M., Matthews, G. V., Mege, J. -L., Meritet, J. -F., Melian, A. M., Martinez, A. M., Neves, J. F., Ng, L. F. P., Medina, Y. N., Cuadros, E. N., Gonzalo Ocejo-Vinyals, J., Pan-Hammarstrom, Q., Richard, J. -C., Riviere, J. G., Rodriguez-Palmero, A., Romero, C. S., del Prado, M. Y. R., Sanchez-Ramon, S., Schweitzer, C. E., Seijo, L. M., Seppanen, M. R. J., Ilovich, A. S., Smadja, D. M., Sole-Violan, J., Taupin, J. -L., Tavernier, S. J., Alvarez, J. T., van de Velde, S., van Praet, J., Silveira, C. D., Debray, M. -P., Lescure, F. -X., Lucet, J. C., Mentre, F., Mohammed, N. S., Tellier, M. -C., Timsit, J. -F., Teoule, F., Puechal, O., Desvallees, M., Enouf, V. V. E., Levy, Y., Ecobichon, J. -L., Amat, K. K. A., Lucet, J. -C., Grobusch, M. P., Hermans, S. M., Hovius, J. W., Prins, J. M., Stijnis, C. S., Joost Wiersinga, W., Algera, A. G., Schultz, M. J., Brouwer, M. C., Bogaard, H. J., Hollmann, M. W., de Jong, M. D., Vlaar, A. P. J., Zwinderman, A. H., Muhsen, S. A., Anderson, M. S., Barrett, K. S., Bustamante, C. D., Cooper, M. A., Derisi, J. L., Drolet, B. A., Franco, J. L., Gregersen, P. K., Henrickson, S. E., Ku, C. -L., Lucas, C. L., Planas, A. M., Uddin, M. J., Vazquez, S. E., Chauvin, S. D., Luthers, C. R., Bauman, B. M., Hupalo, D. M., Wilkerson, M. D., Zhang, Qian [0000-0002-9040-3289], Bastard, Paul [0000-0002-5926-8437], Le Pen, Jeremie [0000-0001-7025-9526], Moncada-Velez, Marcela [0000-0002-3073-5345], Ogishi, Masato [0000-0003-2421-7389], Sabli, Ira K. D. [0000-0002-0170-2990], Hodeib, Stephanie [0000-0002-5978-6189], Korol, Cecilia [0000-0002-0023-8823], Bilguvar, Kaya [0000-0002-7313-7652], Bolze, Alexandre [0000-0001-7399-2766], Bigio, Benedetta [0000-0001-7291-5638], Yang, Rui [0000-0003-4427-2158], Arias, Andrés Augusto [0000-0002-9478-8403], Zhou, Qinhua [0000-0002-5112-3727], Chbihi, Marwa [0000-0002-2771-851X], Bonnet-Madin, Lucie [0000-0002-9848-3287], Dorgham, Karim [0000-0001-9539-3203], Smith, Nikaïa [0000-0002-0202-612X], Schneider, William M. [0000-0001-9407-6118], Razooky, Brandon S. [0000-0002-5263-1512], Hoffmann, Hans-Heinrich [0000-0003-0554-0244], Michailidis, Eleftherios [0000-0002-9907-4346], Han, Jin Eun [0000-0003-1112-9320], Lorenzo, Lazaro [0000-0001-6648-8684], Bizien, Lucy [0000-0001-9163-9122], Meade, Philip [0000-0002-6754-7209], Neehus, Anna-Lena [0000-0002-8573-6820], Ugurbil, Aileen Camille [0000-0002-9450-3092], Kerner, Gaspard [0000-0003-0146-9428], Zhang, Peng [0000-0002-6129-567X], Rapaport, Franck [0000-0001-6553-2110], Manry, Jérémy [0000-0001-5998-2051], Masson, Cecile [0000-0001-7870-7821], Schlüter, Agatha [0000-0001-6732-1528], Le Voyer, Tom [0000-0002-0630-8626], Khan, Taushif [0000-0002-7917-8965], Fellay, Jacques [0000-0002-8240-939X], Roussel, Lucie [0000-0001-5355-702X], Alosaimi, Mohammed F. [0000-0002-8025-3491], Al-Mulla, Fahd [0000-0001-5409-3829], Almourfi, Feras [0000-0002-5166-4662], Alsohime, Fahad [0000-0002-4979-3895], Al Turki, Saeed [0000-0001-7017-336X], Hasanato, Rana [0000-0002-4697-2222], Beek, Diederik van der [0000-0002-4571-044X], Bettini, Laura Rachele [0000-0002-0280-1704], Bonfanti, Paolo [0000-0001-7289-8823], Oler, Andrew J. [0000-0002-6310-0434], Tompkins, Miranda F. [0000-0003-2941-7515], Alba, Camille [0000-0002-0458-1629], Smits, Guillaume [0000-0003-2845-6758], Soler-Palacín, Pere [0000-0002-0346-5570], Martin-Nalda, Andrea [0000-0002-3590-0186], Colobran, Roger [0000-0002-5964-536X], Çölkesen, Fatma [0000-0001-9545-5179], Yasar, Kadriye Kart [0000-0003-2963-4894], Senoglu, Sevtap [0000-0003-4796-9583], Karabela, Şemsi Nur [0000-0003-2562-3004], Rodríguez-Gallego, Carlos [0000-0002-4344-8644], Novelli, Giuseppe [0000-0002-7781-602X], Tandjaoui-Lambiotte, Yacine [0000-0003-1123-4788], and Laouénan, Cédric [0000-0002-3681-6314]
Subjects: Male, COVID19, Interferon Regulatory Factor-7, [SDV]Life Sciences [q-bio], NF-KAPPA-B, Receptor, Interferon alpha-beta, SUSCEPTIBILITY, susceptibility, Interferon alpha-beta, CoV-Contact Cohort, 0302 clinical medicine, Interferon, Loss of Function Mutation, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 80 and over, Medicine and Health Sciences, Viral, Online, Imagine COVID Group, Child, Adolescent, Adult, Aged, Aged, 80 and over, Alleles, Asymptomatic Infections, Betacoronavirus, COVID-19, Child, Preschool, Coronavirus Infections/genetics, Coronavirus Infections/immunology, Female, Genetic Loci, Genetic Predisposition to Disease, Humans, Infant, Interferon Regulatory Factor-7/deficiency, Interferon Regulatory Factor-7/genetics, Interferon Type I/immunology, Middle Aged, Pandemics, Pneumonia, Viral/genetics, Pneumonia, Viral/immunology, Receptor, Interferon alpha-beta/deficiency, Receptor, Interferon alpha-beta/genetics, SARS-CoV-2, Toll-Like Receptor 3/deficiency, Toll-Like Receptor 3/genetics, Young Adult, Research Articles, 0303 health sciences, Multidisciplinary, COVID Clinicians, deficiency, 3. Good health, Multidisciplinary Sciences, DEFICIENCY, Settore MED/03, 030220 oncology & carcinogenesis, Interferon Type I, Science & Technology - Other Topics, medicine.symptom, Coronavirus Infections, Receptor, medicine.drug, NIAID-USUHS, Research Article, General Science & Technology, HERPES-SIMPLEX ENCEPHALITIS, French COVID Cohort Study Group, Pneumonia, Viral, Immunology, Asymptomatic, Virus, 03 medical and health sciences, Immunity, nf-kappa-b, medicine, Genetics, Preschool, COVID Human Genetic Effort, 030304 developmental biology, Biobank, Science & Technology, business.industry, R-Articles, TAGC COVID Immunity Group, Médecine pathologie humaine, herpes-simplex encephalitis, Pneumonia, Amsterdam UMC Covid-19, medicine.disease, COVID-STORM Clinicians, Toll-Like Receptor 3, 3121 General medicine, internal medicine and other clinical medicine, IRF7, 3111 Biomedicine, business, Interferon type I, Interferon regulatory factors
Abstract: COVID-STORM Clinicians Giuseppe Foti1, Giacomo Bellani 1, Giuseppe Citerio1, Ernesto Contro1, Alberto Pesci2, Maria Grazia Valsecchi3, Marina Cazzaniga4 1Department of Emergency, Anesthesia and Intensive Care, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy. 2Department of Pneumology, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy. 3Center of Bioinformatics and Biostatistics, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy. 4Phase I Research Center, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT, COVID Clinicians Jorge Abad1, Sergio Aguilera-Albesa2, Ozge Metin Akcan3, Ilad Alavi Darazam4, Juan C. Aldave5, Miquel Alfonso Ramos6, Seyed Alireza Nadji7, Gulsum Alkan8, Jerome Allardet-Servent9, Luis M. Allende10, Laia Alsina11, Marie-Alexandra Alyanakian12, Blanca Amador-Borrero13, Zahir Amoura14, Arnau Antolí15, Sevket Arslan16, Sophie Assant17, Terese Auguet18, Axelle Azot19, Fanny Bajolle20, Aurélie Baldolli21, Maite Ballester22, Hagit Baris Feldman23, Benoit Barrou24, Alexandra Beurton25, Agurtzane Bilbao26, Geraldine Blanchard-Rohner27, Ignacio Blanco1, Adeline Blandinières28, Daniel Blazquez-Gamero29, Marketa Bloomfield30, Mireia Bolivar-Prados31, Raphael Borie32, Cédric Bosteels33, Ahmed A. Bousfiha34, Claire Bouvattier35, Oksana Boyarchuk36, Maria Rita P. Bueno37, Jacinta Bustamante20, Juan José Cáceres Agra38, Semra Calimli39, Ruggero Capra40, Maria Carrabba41, Carlos Casasnovas42, Marion Caseris43, Martin Castelle44, Francesco Castelli45, Martín Castillo de Vera46, Mateus V. Castro37, Emilie Catherinot47, Martin Chalumeau48, Bruno Charbit49, Matthew P. Cheng50, Père Clavé31, Bonaventura Clotet51, Anna Codina52, Fatih Colkesen53, Fatma Çölkesen54, Roger Colobran55, Cloé Comarmond56, David Dalmau57, David Ross Darley58, Nicolas Dauby59, Stéphane Dauger60, Loic de Pontual61, Amin Dehban62, Geoffroy Delplancq63, Alexandre Demoule64, Jean-Luc Diehl65, Stephanie Dobbelaere66, Sophie Durand67, Waleed Eldars68, Mohamed Elgamal69, Marwa H. Elnagdy70, Melike Emiroglu71, Emine Hafize Erdeniz72, Selma Erol Aytekin73, Romain Euvrard74, Recep Evcen75, Giovanna Fabio41, Laurence Faivre76, Antonin Falck43, Muriel Fartoukh77, Morgane Faure78, Miguel Fernandez Arquero79, Carlos Flores80, Bruno Francois81, Victoria Fumadó82, Francesca Fusco83, Blanca Garcia Solis84, Pascale Gaussem85, Juana Gil-Herrera86, Laurent Gilardin87, Monica Girona Alarcon88, Mònica Girona-Alarcón88, Jean-Christophe Goffard89, Funda Gok90, Rafaela González-Montelongo91, Antoine Guerder92, Yahya Gul93, Sukru Nail Guner93, Marta Gut94, Jérôme Hadjadj95, Filomeen Haerynck96, Rabih Halwani97, Lennart Hammarström98, Nevin Hatipoglu99, Elisa Hernandez-Brito100, Cathérine Heijmans101, María Soledad Holanda-Peña102, Juan Pablo Horcajada103, Levi Hoste104, Eric Hoste105, Sami Hraiech106, Linda Humbert107, Alejandro D. Iglesias108, Antonio Íñigo-Campos91, Matthieu Jamme109, María Jesús Arranz110, Iolanda Jordan111, Philippe Jorens112, Fikret Kanat113, Hasan Kapakli114, Iskender Kara115, Adem Karbuz116, Kadriye Kart Yasar117, Sevgi Keles118, Yasemin Kendir Demirkol119, Adam Klocperk120, Zbigniew J. Król121, Paul Kuentz122, Yat Wah M. Kwan123, Jean-Christophe Lagier124, Bart N. Lambrecht33, Yu-Lung Lau125, Fleur Le Bourgeois60, Yee-Sin Leo126, Rafael Leon Lopez127, Daniel Leung125, Michael Levin128, Michael Levy60, Romain Lévy20, Zhi Li49, Agnes Linglart129, Bart Loeys130, José M. Lorenzo-Salazar91, Céline Louapre131, Catherine Lubetzki131, Charles-Edouard Luyt132, David C. Lye133, Davood Mansouri134, Majid Marjani135, Jesus Marquez Pereira136, Andrea Martin137, David Martínez Pueyo138, Javier Martinez-Picado139, Iciar Marzana140, Alexis Mathian14, Larissa R. B. Matos37, Gail V. Matthews141, Julien Mayaux142, Jean-Louis Mège143, Isabelle Melki144, Jean-François Meritet145, Ozge Metin146, Isabelle Meyts147, Mehdi Mezidi148, Isabelle Migeotte149, Maude Millereux150, Tristan Mirault151, Clotilde Mircher67, Mehdi Mirsaeidi152, Abián Montesdeoca Melián153, Antonio Morales Martinez154, Pierre Morange155, Clémence Mordacq107, Guillaume Morelle156, Stéphane Mouly13, Adrián Muñoz-Barrera91, Leslie Naesens157, Cyril Nafati158, João Farela Neves159, Lisa FP. Ng160, Yeray Novoa Medina161, Esmeralda Nuñez Cuadros162, J. Gonzalo Ocejo-Vinyals163, Zerrin Orbak164, Mehdi Oualha20, Tayfun Özçelik165, Qiang Pan-Hammarström166, Christophe Parizot142, Tiffany Pascreau167, Estela Paz-Artal168, Sandra Pellegrini49, Rebeca Pérez de Diego84, Aurélien Philippe169, Quentin Philippot77, Laura Planas-Serra170, Dominique Ploin171, Julien Poissy172, Géraldine Poncelet43, Marie Pouletty173, Paul Quentric142, Didier Raoult143, Anne-Sophie Rebillat67, Ismail Reisli174, Pilar Ricart175, Jean-Christophe Richard176, Nadia Rivet28, Jacques G. Rivière177, Gemma Rocamora Blanch15, Carlos Rodrigo1, Carlos Rodriguez-Gallego178, Agustí Rodríguez-Palmero179, Carolina Soledad Romero180, Anya Rothenbuhler181, Flore Rozenberg182, Maria Yolanda Ruiz del Prado183, Joan Sabater Riera15, Oliver Sanchez184, Silvia Sánchez-Ramón185, Agatha Schluter170, Matthieu Schmidt186, Cyril E. Schweitzer187, Francesco Scolari188, Anna Sediva189, Luis M. Seijo190, Damien Sene13, Sevtap Senoglu117, Mikko R. J. Seppänen191, Alex Serra Ilovich192, Mohammad Shahrooei62, Hans Slabbynck193, David M. Smadja194, Ali Sobh195, Xavier Solanich Moreno15, Jordi Solé-Violán196, Catherine Soler197, Pere Soler-Palacín137, Yuri Stepanovskiy198, Annabelle Stoclin199, Fabio Taccone149, Yacine Tandjaoui-Lambiotte200, Jean-Luc Taupin201, Simon J. Tavernier202, Benjamin Terrier203, Caroline Thumerelle107, Gabriele Tomasoni204, Julie Toubiana48, Josep Trenado Alvarez205, Sophie Trouillet-Assant206, Jesús Troya207, Alessandra Tucci208, Matilde Valeria Ursini‬83, Yurdagul Uzunhan209, Pierre Vabres210, Juan Valencia-Ramos211, Eva Van Braeckel33, Stijn Van de Velde212, Ana Maria Van Den Rym84, Jens Van Praet213, Isabelle Vandernoot214, Hulya Vatansev215, Valentina Vélez-Santamaria42, Sébastien Viel171, Cédric Vilain216, Marie E. Vilaire67, Audrey Vincent35, Guillaume Voiriot217, Fanny Vuotto107, Alper Yosunkaya90, Barnaby E. Young126, Fatih Yucel218, Faiez Zannad219, Mayana Zatz37, Alexandre Belot220*, Imagine COVID Group Christine Bole-Feysot, Stanislas Lyonnet*, Cécile Masson, Patrick Nitschke, Aurore Pouliet, Yoann Schmitt, Frederic Tores, Mohammed Zarhrate Imagine Institute, Université de Paris, INSERM UMR 1163, Paris, France. *Leader of the Imagine COVID Group., French COVID Cohort Study Group Laurent Abel1, Claire Andrejak2, François Angoulvant3, Delphine Bachelet4, Romain Basmaci5, Sylvie Behillil6, Marine Beluze7, Dehbia Benkerrou8, Krishna Bhavsar4, François Bompart9, Lila Bouadma4, Maude Bouscambert10, Mireille Caralp11, Minerva Cervantes-Gonzalez12, Anissa Chair4, Alexandra Coelho13, Camille Couffignal4, Sandrine Couffin-Cadiergues14, Eric D’Ortenzio12, Charlene Da Silveira4, Marie-Pierre Debray4, Dominique Deplanque15, Diane Descamps16, Mathilde Desvallées17, Alpha Diallo18, Alphonsine Diouf13, Céline Dorival8, François Dubos19, Xavier Duval4, Philippine Eloy4, Vincent VE Enouf20, Hélène Esperou21, Marina Esposito-Farese4, Manuel Etienne22, Nadia Ettalhaoui4, Nathalie Gault4, Alexandre Gaymard10, Jade Ghosn4, Tristan Gigante23, Isabelle Gorenne4, Jérémie Guedj24, Alexandre Hoctin13, Isabelle Hoffmann4, Salma Jaafoura21, Ouifiya Kafif4, Florentia Kaguelidou25, Sabina Kali4, Antoine Khalil4, Coralie Khan17, Cédric Laouénan4, Samira Laribi4, Minh Le4, Quentin Le Hingrat4, Soizic Le Mestre18, Hervé Le Nagard24, François-Xavier Lescure4, Yves Lévy26, Claire Levy-Marchal27, Bruno Lina10, Guillaume Lingas24, Jean Christophe Lucet4, Denis Malvy28, Marina Mambert13, France Mentré4, Noémie Mercier18, Amina Meziane8, Hugo Mouquet20, Jimmy Mullaert4, Nadège Neant24, Marion Noret29, Justine Pages30, Aurélie Papadopoulos21, Christelle Paul18, Nathan Peiffer-Smadja4, Ventzislava Petrov-Sanchez18, Gilles Peytavin4, Olivier Picone31, Oriane Puéchal12, Manuel Rosa-Calatrava10, Bénédicte Rossignol23, Patrick Rossignol32, Carine Roy4, Marion Schneider4, Caroline Semaille12, Nassima Si Mohammed4, Lysa Tagherset4, Coralie Tardivon4, Marie-Capucine Tellier4, François Téoulé8, Olivier Terrier10, Jean-François Timsit4, Théo Trioux4, Christelle Tual33, Sarah Tubiana4, Sylvie van der Werf34, Noémie Vanel35, Aurélie Veislinger33, Benoit Visseaux16, Aurélie Wiedemann26, Yazdan Yazdanpanah36 1Inserm UMR 1163, Paris, France. 2CHU Amiens, France. 3Hôpital Necker, Paris, France. 4Hôpital Bichat, Paris, France. 5Hôpital Louis Mourrier, Colombes, France. 6Institut Pasteur, Paris, France. 7F-CRIN Partners Platform, AP-HP, Université de Paris, Paris, France. 8Inserm UMR 1136, Paris, France. 9Drugs for Neglected Diseases Initiative, Geneva, Switzerland. 10Inserm UMR 1111, Lyon, France. 11Inserm Transfert, Paris, France. 12REACTing, Paris, France. 13Inserm UMR 1018, Paris, France. 14Inserm, Pôle Recherche Clinique, Paris, France. 15CIC 1403 Inserm-CHU Lille, Paris, France. 16Université de Paris, IAME, INSERM UMR 1137, AP-HP, University Hospital Bichat Claude Bernard, Virology, Paris, France. 17Inserm UMR 1219, Bordeaux, France. 18ANRS, Paris, France. 19CHU Lille, Lille, France. 20Pasteur Institute, Paris, France. 21Inserm sponsor, Paris, France. 22CHU Rouen–SMIT, Rouen, France. 23FCRIN INI-CRCT, Nancy, France. 24Inserm UMR 1137, Paris, France. 25Centre d’Investigation Clinique, Inserm CIC1426, Hôpital Robert Debré, Paris, France. 26Inserm UMR 955, Créteil, France; Vaccine Research Instiute (VRI), Paris, France. 27F-CRIN INI-CRCT, Paris, France. 28CHU de Bordeaux–SMIT, Bordeaux, France. 29RENARCI, Annecy, France. 30Hôpital Robert Debré, Paris, France. 31Hôpital Louis Mourier–Gynécologie, Colombes, France. 32University of Lorraine, Plurithematic Clinical Investigation Centre Inserm CIC-P; 1433, Inserm U1116, CHRU Nancy Hopitaux de Brabois, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France. 33Inserm CIC-1414, Rennes, France. 34Institut Pasteur, UMR 3569 CNRS, Université de Paris, Paris, France. 35Hôpital la Timone, Marseille, France. 36Bichat–SMIT, Paris, France., CoV-Contact Cohort Loubna Alavoine1, Karine K. A. Amat2, Sylvie Behillil3, Julia Bielicki4, Patricia Bruijning5, Charles Burdet6, Eric Caumes7, Charlotte Charpentier8, Bruno Coignard9, Yolande Costa1, Sandrine Couffin-Cadiergues10, Florence Damond8, Aline Dechanet11, Christelle Delmas10, Diane Descamps8, Xavier Duval1, Jean-Luc Ecobichon1, Vincent Enouf3, Hélène Espérou10, Wahiba Frezouls1, Nadhira Houhou11, Emila Ilic-Habensus1, Ouifiya Kafif11, John Kikoine11, Quentin Le Hingrat8, David Lebeaux12, Anne Leclercq1, Jonathan Lehacaut1, Sophie Letrou1, Bruno Lina13, Jean-Christophe Lucet14, Denis Malvy15, Pauline Manchon11, Milica Mandic1, Mohamed Meghadecha16, Justina Motiejunaite17, Mariama Nouroudine1, Valentine Piquard11, Andreea Postolache11, Caroline Quintin1, Jade Rexach1, Layidé Roufai10, Zaven Terzian11, Michael Thy18, Sarah Tubiana1, Sylvie van der Werf3, Valérie Vignali1, Benoit Visseaux8, Yazdan Yazdanpanah14 1Centre d’Investigation Clinique, Inserm CIC 1425, Hôpital Bichat Claude Bernard, APHP, Paris, France. 2IMEA Fondation Léon M’Ba, Paris, France. 3Institut Pasteur, UMR 3569 CNRS, Université de Paris, Paris, France. 4University of Basel Children’s Hospital. 5Julius Center for Health Sciences and Primary Care, Utrecht, Netherlands. 6Université de Paris, IAME, Inserm UMR 1137, F-75018, Paris, France, Hôpital Bichat Claude Bernard, APHP, Paris, France. 7Hôpital Pitiè Salpétriere, APHP, Paris. 8Université de Paris, IAME, INSERM UMR 1137, AP-HP, University Hospital Bichat Claude Bernard, Virology, Paris, France. 9Santé Publique France, Saint Maurice, France. 10Pole Recherche Clinique, Inserm, Paris, France. 11Hôpital Bichat Claude Bernard, APHP, Paris, France. 12APHP, Paris, France. 13Virpath Laboratory, International Center of Research in Infectiology, Lyon University, INSERM U1111, CNRS UMR 5308, ENS, UCBL, Lyon, France. 14IAME Inserm UMR 1138, Hôpital Bichat Claude Bernard, APHP, Paris, France. 15Service des Maladies Infectieuses et Tropicales; Groupe Pellegrin-Place Amélie-Raba-Léon, Bordeaux, France. 16Hôpital Hotel Dieu, APHP, Paris, France. 17Service des Explorations Fonctionnelles, Hôpital Bichat–Claude Bernard, APHP, Paris, France. 18Center for Clinical Investigation, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital, Paris, France., Amsterdam UMC Covid-19 Biobank Michiel van Agtmael1, Anna Geke Algera2, Frank van Baarle2, Diane Bax3, Martijn Beudel4, Harm Jan Bogaard5, Marije Bomers1, Lieuwe Bos2, Michela Botta2, Justin de Brabander6, Godelieve de Bree6, Matthijs C. Brouwer4, Sanne de Bruin2, Marianna Bugiani7, Esther Bulle2, Osoul Chouchane1, Alex Cloherty3, Paul Elbers2, Lucas Fleuren2, Suzanne Geerlings1, Bart Geerts8, Theo Geijtenbeek9, Armand Girbes2, Bram Goorhuis1, Martin P. Grobusch1, Florianne Hafkamp9, Laura Hagens2, Jorg Hamann10, Vanessa Harris1, Robert Hemke11, Sabine M. Hermans1, Leo Heunks2, Markus W. Hollmann8, Janneke Horn2, Joppe W. Hovius1, Menno D. de Jong12, Rutger Koning4, Niels van Mourik2, Jeaninne Nellen1, Frederique Paulus2, Edgar Peters1, Tom van der Poll1, Benedikt Preckel8, Jan M. Prins1, Jorinde Raasveld2, Tom Reijnders1, Michiel Schinkel1, Marcus J. Schultz2, Alex Schuurman13, Kim Sigaloff1, Marry Smit2, Cornelis S. Stijnis1, Willemke Stilma2, Charlotte Teunissen14, Patrick Thoral2, Anissa Tsonas2, Marc van der Valk1, Denise Veelo8, Alexander P.J. Vlaar15, Heder de Vries2, Michèle van Vugt1, W. Joost Wiersinga1, Dorien Wouters16, A. H. (Koos) Zwinderman17, Diederik van de Beek4* 1Department of Infectious Diseases, Amsterdam UMC, Amsterdam, Netherlands. 2Department of Intensive Care, Amsterdam UMC, Amsterdam, Netherlands. 3Experimental Immunology, Amsterdam UMC, Amsterdam, Netherlands. 4Department of Neurology, Amsterdam UMC, Amsterdam Neuroscience, Amsterdam, Netherlands. 5Department of Pulmonology, Amsterdam UMC, Amsterdam, Netherlands. 6Department of Infectious Diseases, Amsterdam UMC, Amsterdam, Netherlands. 7Department of Pathology, Amsterdam UMC, Amsterdam, Netherlands. 8Department of Anesthesiology, Amsterdam UMC, Amsterdam, Netherlands. 9Department of Experimental Immunology, Amsterdam UMC, Amsterdam, Netherlands. 10Amsterdam UMC Biobank Core Facility, Amsterdam UMC, Amsterdam, Netherlands. 11Department of Radiology, Amsterdam UMC, Amsterdam, Netherlands. 12Department of Medical Microbiology, Amsterdam UMC, Amsterdam, Netherlands. 13Department of Internal Medicine, Amsterdam UMC, Amsterdam, Netherlands. 14Neurochemical Laboratory, Amsterdam UMC, Amsterdam, Netherlands. 15Department of Intensive Care, Amsterdam UMC, Amsterdam, Netherlands. 16Department of Clinical Chemistry, Amsterdam UMC, Amsterdam, Netherlands. 17Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, Amsterdam, Netherlands. 18Department of Neurology, Amsterdam UMC, Amsterdam, Netherlands. *Leader of the AMC Consortium., COVID Human Genetic Effort Laurent Abel1, Alessandro Aiuti2, Saleh Al Muhsen3, Fahd Al-Mulla4, Mark S. Anderson5, Andrés Augusto Arias6, Hagit Baris Feldman7, Dusan Bogunovic8, Alexandre Bolze9, Anastasiia Bondarenko10, Ahmed A. Bousfiha11, Petter Brodin12, Yenan Bryceson12, Carlos D. Bustamante13, Manish Butte14, Giorgio Casari15, Samya Chakravorty16, John Christodoulou17, Elizabeth Cirulli9, Antonio Condino-Neto18, Megan A. Cooper19, Clifton L. Dalgard20, Alessia David21, Joseph L. DeRisi22, Murkesh Desai23, Beth A. Drolet24, Sara Espinosa25, Jacques Fellay26, Carlos Flores27, Jose Luis Franco28, Peter K. Gregersen29, Filomeen Haerynck30, David Hagin31, Rabih Halwani32, Jim Heath33, Sarah E. Henrickson34, Elena Hsieh35, Kohsuke Imai36, Yuval Itan8, Timokratis Karamitros37, Kai Kisand38, Cheng-Lung Ku39, Yu-Lung Lau40, Yun Ling41, Carrie L. Lucas42, Tom Maniatis43, Davoud Mansouri44, Laszlo Marodi45, Isabelle Meyts46, Joshua Milner47, Kristina Mironska48, Trine Mogensen49, Tomohiro Morio50, Lisa FP. Ng51, Luigi D. Notarangelo52, Antonio Novelli53, Giuseppe Novelli54, Cliona O’Farrelly55, Satoshi Okada56, Tayfun Ozcelik57, Rebeca Perez de Diego58, Anna M. Planas59, Carolina Prando60, Aurora Pujol61, Lluis Quintana-Murci62, Laurent Renia63, Alessandra Renieri64, Carlos Rodríguez-Gallego65, Vanessa Sancho-Shimizu66, Vijay Sankaran67, Kelly Schiabor Barrett9, Mohammed Shahrooei68, Andrew Snow69, Pere Soler-Palacín70, András N. Spaan71, Stuart Tangye72, Stuart Turvey73, Furkan Uddin74, Mohammed J. Uddin75, Diederik van de Beek76, Sara E. Vazquez77, Donald C. Vinh78, Horst von Bernuth79, Nicole Washington9, Pawel Zawadzki80, Helen C. Su52, Jean-Laurent Casanova81 1INSERM U1163, University of Paris, Imagine Institute, Paris, France. 2San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele, Milan, Italy. 3King Saud University, Riyadh, Saudi Arabia. 4Kuwait University, Kuwait City, Kuwait. 5University of California, San Francisco, San Francisco, CA, USA. 6Universidad de Antioquia, Group of Primary Immunodeficiencies, Antioquia, Colombia. 7The Genetics Institute, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 8Icahn School of Medicine at Mount Sinai, New York, NY, USA. 9Helix, San Mateo, CA, USA. 10Shupyk National Medical Academy for Postgraduate Education, Kiev, Ukraine. 11Clinical Immunology Unit, Pediatric Infectious Disease Departement, Faculty of Medicine and Pharmacy, Averroes University Hospital; LICIA Laboratoire d’Immunologie Clinique, d’Inflammation et d’Allergie, Hassann Ii University, Casablanca, Morocco. 12Karolinska Institute, Stockholm, Sweden. 13Stanford University, Stanford, CA, USA. 14University of California, Los Angeles, CA, USA. 15Medical Genetics, IRCCS Ospedale San Raffaele, Milan, Italy. 16Emory University Department of Pediatrics and Children’s Healthcare of Atlanta, Atlanta, GA, USA. 17Murdoch Children’s Research Institute, Victoria, Australia. 18University of São Paulo, São Paulo, Brazil. 19Washington University School of Medicine, St. Louis, MO, USA. 20The American Genome Center; Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 21Centre for Bioinformatics and System Biology, Department of Life Sciences, Imperial College London, South Kensington Campus, London, UK. 22University of California, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA. 23Bai Jerbai Wadia Hospital for Children, Mumbai, India. 24School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA. 25Instituto Nacional de Pediatria (National Institute of Pediatrics), Mexico City, Mexico. 26Swiss Federal Institute of Technology Lausanne, Lausanne, Switzerland. 27Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Canarian Health System, Santa Cruz de Tenerife, Spain. 28University of Antioquia, Medellín, Colombia. 29Feinstein Institute for Medical Research, Northwell Health USA, Manhasset, NY, USA. 30Department of Paediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency Ghent (CPIG), PID Research Lab, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Edegem, Belgium. 31The Genetics Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 32Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, UAE. 33Institute for Systems Biology, Seattle, WA, USA. 34Children’s Hospital of Philadelphia, Philadelphia, PA, USA. 35Anschutz Medical Campus, Aurora, CO, USA. 36Riken, Tokyo, Japan. 37Hellenic Pasteur Institute, Athens, Greece. 38University of Tartu, Tartu, Estonia. 39Chang Gung University, Taoyuan County, Taiwan. 40The University of Hong Kong, Hong Kong, China. 41Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 42Yale School of Medicine, New Haven, CT, USA. 43New York Genome Center, New York, NY, USA. 44Shahid Beheshti University of Medical Sciences, Tehran, Iran. 45Semmelweis University Budapest, Budapest, Hungary. 46KU Leuven, Department of Immunology, Microbiology and Transplantation, Leuven, Belgium. 47Columbia University Medical Center, New York, NY, USA. 48University Clinic for Children’s Diseases, Skopje, North Macedonia. 49Aarhus University, Aarhus, Denmark. 50Tokyo Medical & Dental University Hospital, Tokyo, Japan. 51Singapore Immunology Network, Singapore. 52National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 53Bambino Gesù Children’s Hospital, Rome, Italy. 54Department of Biomedicine and Prevention, University of Rome “Tor Vergata,” Rome, Italy. 55Trinity College, Dublin, Ireland. 56Hiroshima University, Hiroshima, Japan. 57Bilkent University, Ankara, Turkey. 58Laboratory of Immunogenetics of Human Diseases, Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid, Spain. 59IIBB-CSIC, IDIBAPS, Barcelona, Spain. 60Faculdades Pequeno Príncipe e Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Brazil. 61Neurometabolic Diseases Laboratory, IDIBELL–Hospital Duran I Reynals; Catalan Institution for Research and Advanced Studies (ICREA); CIBERER U759, ISCiii Madrid Spain, Barcelona, Spain. 62Institut Pasteur (CNRS UMR2000) and Collège de France, Paris, France. 63Infectious Diseases Horizontal Technology Center and Singapore Immunology Network, Agency for Science Technology (A*STAR), Singapore. 64Medical Genetics, University of Siena, Siena, Italy; Genetica Medica, Azienda Ospedaliero-Universitaria Senese, Italy; GEN-COVID Multicenter Study. 65Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Canary Islands, Spain. 66Imperial College London, London, UK. 67Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA. 68Saeed Pathobiology and Genetic Lab, Tehran, Iran. 69Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 70Hospital Universitari Vall d’Hebron, Barcelona, Spain. 71University Medical Center Utrecht, Amsterdam, The Netherlands. 72Garvan Institute of Medical Research, Sydney, Australia. 73The University of British Columbia, Vancouver, Canada. 74Holy Family Red Crescent Medical College; Centre for Precision Therapeutics, NeuroGen Children’s Healthcare; Genetics and Genomic Medicine Centre, NeuroGen Children’s Healthcare, Dhaka, Bangladesh. 75Mohammed Bin Rashid University of Medicine and Health Sciences, College of Medicine, Dubai, UAE; The Centre for Applied Genomics, Department of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada. 76Amsterdam UMC, University of Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam, The Netherlands. 77University of California, San Francisco, CA, USA. 78McGill University Health Centre, Montreal, Canada. 79Charité–Berlin University Hospital Center, Berlin, Germany. 80Molecular Biophysics Division, Faculty of Physics, A. Mickiewicz University, Uniwersytetu Poznanskiego 2, Poznań, Poland. 81Rockefeller University, Howard Hughes Medical Institute, Necker Hospital, New York, NY, USA. *Leaders of the COVID Human Genetic Effort., NIAID-USUHS/TAGC COVID Immunity Group Huie Jing1,2, Wesley Tung1,2, Christopher R. Luthers3, Bradly M. Bauman3, Samantha Shafer2,4, Lixin Zheng2,4, Zinan Zhang2,4, Satoshi Kubo2,4, Samuel D. Chauvin2,4, Kazuyuki Meguro1,2, Elana Shaw1,2, Michael Lenardo2,4, Justin Lack5, Eric Karlins6, Daniel M. Hupalo7, John Rosenberger7, Gauthaman Sukumar7, Matthew D. Wilkerson7, Xijun Zhang7 1Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. 2NIAID Clinical Genomics Program, National Institutes of Health, Bethesda, MD, USA. 3Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 4Laboratory of Immune System Biology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. 5NIAID Collaborative Bioinformatics Resource, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA. 6Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD, USA. 7The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, MD, USA., Clinical outcome upon infection with SARS-CoV-2 ranges from silent infection to lethal COVID-19. We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern TLR3- and IRF7-dependent type I interferon (IFN) immunity to influenza virus, in 659 patients with life-threatening COVID-19 pneumonia, relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally define LOF variants in 23 patients (3.5%), aged 17 to 77 years, underlying autosomal recessive or dominant deficiencies. We show that human fibroblasts with mutations affecting this pathway are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection., We thank the generous donation from Fisher Center for Alzheimer’s Research Foundation for our research. The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project, ANRS-COV05, the Square Foundation, Grandir - Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, Institut National de la Santé et de la Recherche Médicale (INSERM), the University of Paris. The French COVID Cohort study group was sponsored by Inserm and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). Regione Lombardia, Italy (project “Risposta immune in pazienti con COVID-19 e co-morbidità”), and the Intramural Research Program of the NIAID, NIH. The laboratory of Genomes & Cell Biology of Disease is supported by “Integrative Biology of Emerging Infectious Diseases” (grant no. ANR-10-LABX-62-IBEID), the “Fondation pour la Recherche Medicale” (grant FRM - EQU202003010193), the “Agence Nationale de la Recherche” (ANR FLASH COVID project IDISCOVR cofounded by the “Fondation pour la Recherche Médicale”), University of Paris (“Plan de Soutien Covid-19”: RACPL20FIR01-COVID-SOUL). IM is a senior clinical investigator with the FWO Vlaanderen; IM and LM are supported by FWO G0C8517N – GOB5120N. The VS team was supported by “Agence Nationale de la Recherche” (ANR-17-CE15-0003, ANR-17-CE15-0003-01), and by Université de Paris “PLAN D’URGENCE COVID19”. LK was supported by a fellowship from the French Ministry of Research. VS-S is supported by a UKRI Future Leaders Fellowship (MR/S032304/1). SZA-M is supported by the Elite Journals Program at King Saud University through grant number PEJP-16-107. JM lab is supported by Columbia University COVID biobank and grant: UL1TR001873. Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1, a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. JLP is supported by a European Molecular Biology Organization Long-Term Fellowship (ALTF 380-2018). Work at the Neurometabolic Diseases Laboratory received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 824110 (EasiGenomics grant COVID-19/ PID12342) to A.P., and Roche and Illumina Covid Match Funds to M.G.. C.R.G and colleagues are supported by cInstituto de Salud Carlos III (COV20_01333 and COV20_01334), Spanish Ministry of Science and Innovation, with the funding of European Regional Development Fund-European Social Fund -FEDER-FSE; (RTC-2017-6471-1; AEI/FEDER, UE), and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). D.C.V. is supported by the Fonds de la recherche en santé du Québec clinician-scientist scholar program. Helen Su is adjunct faculty at the University of Pennsylvania. A-L.N. was supported by the Foundation Bettencourt Schueller. The Amsterdam UMC Covid-19 Biobank was funded by the Netherlands Organization for Health Research and Development (ZonMw, NWO-vici 91819627), The Corona Research Fund (Amsterdam UMC), Dr. J. C. Vaillantfonds, and Amsterdam UMC. Work on COVID-19 at the AG-S lab is partly supported by NIH supplements to grants U19AI135972, U19AI142733 and R35 HL135834, and to contract HHSN272201800048C, by a DoD supplement to grant W81XWH-20-1-0270, by DARPA project HR0011-19-2-0020, by CRIP (Center for Research on Influenza Pathogenesis), a NIAID funded Center of Excellence for Influenza Research and Surveillance (CEIRS, contract HHSN272201400008C), by an NIAID funded Collaborative Influenza Vaccine Innovation Center (SEM-CIVIC, contract 75N93019C00051) and by the generous support of the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611(5384)) and anonymous donors. The Virscan analysis presented in fig. S11 was performed with financial support from Sidra Medicine
Published: 2020

5. 647: Tensin 1 is a modifier gene for low BMI in homozygous [F508del]CFTR patients

Author: Walton, N., primary, Zhang, X., additional, Soltis, A., additional, Starr, J., additional, Dalgard, C., additional, Wilkerson, M., additional, Conrad, D., additional, and Pollard, H., additional
Published: 2021
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6. Auto-antibodies against type I IFNs in patients with life-threatening COVID-19

Author: Bastard, P., Rosen, L. B., Zhang, Q., Michailidis, E., Hoffmann, H. -H., Zhang, Y., Dorgham, K., Philippot, Q., Rosain, J., Beziat, V., Manry, J., Shaw, E., Haljasmagi, L., Peterson, P., Lorenzo, L., Bizien, L., Trouillet-Assant, S., Dobbs, K., de Jesus, A. A., Belot, A., Kallaste, A., Catherinot, E., Tandjaoui-Lambiotte, Y., Le Pen, J., Kerner, G., Bigio, B., Seeleuthner, Y., Yang, R., Bolze, A., Spaan, A. N., Delmonte, O. M., Abers, M. S., Aiuti, A., Casari, G., Lampasona, V., Piemonti, L., Ciceri, F., Bilguvar, K., Lifton, R. P., Vasse, M., Smadja, D. M., Migaud, M., Hadjadj, J., Terrier, B., Duffy, D., Quintana-Murci, L., van de Beek, D., Roussel, L., Vinh, D. C., Tangye, S. G., Haerynck, F., Dalmau, D., Martinez-Picado, J., Brodin, P., Nussenzweig, M. C., Boisson-Dupuis, S., Rodriguez-Gallego, C., Vogt, G., Mogensen, T. H., Oler, A. J., Gu, J., Burbelo, P. D., Cohen, J. I., Biondi, A., Bettini, L. R., Dangio, M., Bonfanti, P., Rossignol, P., Mayaux, J., Rieux-Laucat, F., Husebye, E. S., Fusco, F., Ursini, M. V., Imberti, L., Sottini, A., Paghera, S., Quiros-Roldan, E., Rossi, C., Castagnoli, R., Montagna, D., Licari, A., Marseglia, G. L., Duval, X., Ghosn, J., Tsang, J. S., Goldbach-Mansky, R., Kisand, K., Lionakis, M. S., Puel, A., Zhang, S. -Y., Holland, S. M., Gorochov, G., Jouanguy, E., Rice, C. M., Cobat, A., Notarangelo, L. D., Abel, L., H. C., Su, Casanova, J. -L., Arias, A. A., Boisson, B., Boucherit, S., Bustamante, J., Chbihi, M., Chen, J., Chrabieh, M., Kochetkov, T., Le Voyer, T., Liu, D., Nemirovskaya, Y., Ogishi, M., Papandrea, D., Patissier, C., Rapaport, F., Roynard, M., Vladikine, N., Woollett, M., Zhang, P., Kashyap, A., Ding, L., Bosticardo, M., Wang, Q., Ochoa, S., Liu, H., Chauvin, S. D., Stack, M., Koroleva, G., Bansal, N., Dalgard, C. L., Snow, A. L., Abad, J., Aguilera-Albesa, S., Akcan, O. M., Darazam, I. A., Aldave, J. C., Ramos, M. A., Nadji, S. A., Alkan, G., Allardet-Servent, J., Allende, L. M., Alsina, L., Alyanakian, M. -A., Amador-Borrero, B., Amoura, Z., Antoli, A., Arslan, S., Assant, S., Auguet, T., Azot, A., Bajolle, F., Baldolli, A., Ballester, M., Feldman, H. B., Barrou, B., Beurton, A., Bilbao, A., Blanchard-Rohner, G., Blanco, I., Blandinieres, A., Blazquez-Gamero, D., Bloomfield, M., Bolivar-Prados, M., Borie, R., Bousfiha, A. A., Bouvattier, C., Boyarchuk, O., Bueno, M. R. P., Agra, J. J. C., Calimli, S., Capra, R., Carrabba, M., Casasnovas, C., Caseris, M., Castelle, M., Castelli, F., de Vera, M. C., Castro, M. V., Chalumeau, M., Charbit, B., Cheng, M. P., Clave, P., Clotet, B., Codina, A., Colkesen, F., Colobran, R., Comarmond, C., Corsico, A. G., Darley, D. R., Dauby, N., Dauger, S., de Pontual, L., Dehban, A., Delplancq, G., Demoule, A., Di Sabatino, A., Diehl, J. -L., Dobbelaere, S., Durand, S., Eldars, W., Elgamal, M., Elnagdy, M. H., Emiroglu, M., Erdeniz, E. H., Aytekin, S. E., Euvrard, R., Evcen, R., Fabio, G., Faivre, L., Falck, A., Fartoukh, M., Faure, M., Arquero, M. F., Flores, C., Francois, B., Fumado, V., Solis, B. G., Gaussem, P., Gil-Herrera, J., Gilardin, L., Alarcon, M. G., Girona-Alarcon, M., Goffard, J. -C., Gok, F., Gonzalez-Montelongo, R., Guerder, A., Gul, Y., Guner, S. N., Gut, M., Halwani, R., Hammarstrom, L., Hatipoglu, N., Hernandez-Brito, E., Holanda-Pena, M. S., Horcajada, J. P., Hraiech, S., Humbert, L., Iglesias, A. D., Inigo-Campos, A., Jamme, M., Arranz, M. J., Jordan, I., Kanat, F., Kapakli, H., Kara, I., Karbuz, A., Yasar, K. K., Keles, S., Demirkol, Y. K., Klocperk, A., Krol, Z. J., Kuentz, P., Kwan, Y. W. M., Lagier, J. -C., Lau, Y. -L., Le Bourgeois, F., Leo, Y. -S., Lopez, R. L., Leung, D., Levin, M., Levy, M., Levy, R., Li, Z., Linglart, A., Lorenzo-Salazar, J. M., Louapre, C., Lubetzki, C., Luyt, C. -E., Lye, D. C., Mansouri, D., Marjani, M., Pereira, J. M., Martin, A., Pueyo, D. M., Marzana, I., Mathian, A., Matos, L. 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C., Malvy, D., Mambert, M., Mentre, F., Mercier, N., Meziane, A., Mouquet, H., Mullaert, J., Neant, N., Noret, M., Pages, J., Papadopoulos, A., Paul, C., Peiffer-Smadja, N., Petrov-Sanchez, V., Peytavin, G., Picone, O., Puechal, O., Rosa-Calatrava, M., Rossignol, B., Roy, C., Schneider, M., Semaille, C., Mohammed, N. S., Tagherset, L., Tardivon, C., Tellier, M. -C., Teoule, F., Terrier, O., Timsit, J. -F., Treoux, T., Tual, C., Tubiana, S., van der Werf, S., Vanel, N., Veislinger, A., Visseaux, B., Wiedemann, A., Yazdanpanah, Y., Abelc, L., Alcover, A., Aschard, H., Astrom, K., Bousso, P., Bruhns, P., Cumano, A., Demangel, C., Deriano, L., Santo, J. D., Dromer, F., Eberl, G., Enninga, J., Fellay, J., Gomperts-Boneca, I., Hasan, M., Hercberg, S., Lantz, O., Patin, E., Pellegrini, S., Pol, S., Rausell, A., Rogge, L., Sakuntabhai, A., Schwartz, O., Schwikowski, B., Shorte, S., Tangy, F., Toubert, A., Touvier, M., Ungeheuer, M. -N., Albert, M. L., Alavoine, L., Amat, K. K. 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C., Casanovaa, J. -L., Bastard, Paul, Rosen, Lindsey B, Zhang, Qian, Michailidis, Eleftherio, Hoffmann, Hans-Heinrich, Zhang, Yu, Dorgham, Karim, Philippot, Quentin, Rosain, Jérémie, Béziat, Vivien, Manry, Jérémy, Shaw, Elana, Haljasmägi, Lii, Peterson, Pärt, Lorenzo, Lazaro, Bizien, Lucy, Trouillet-Assant, Sophie, Dobbs, Kerry, de Jesus, Adriana Almeida, Belot, Alexandre, Kallaste, Anne, Catherinot, Emilie, Tandjaoui-Lambiotte, Yacine, Le Pen, Jeremie, Kerner, Gaspard, Bigio, Benedetta, Seeleuthner, Yoann, Yang, Rui, Bolze, Alexandre, Spaan, András N, Delmonte, Ottavia M, Abers, Michael S, Aiuti, Alessandro, Casari, Giorgio, Lampasona, Vito, Piemonti, Lorenzo, Ciceri, Fabio, Bilguvar, Kaya, Lifton, Richard P, Vasse, Marc, Smadja, David M, Migaud, Mélanie, Hadjadj, Jérome, Terrier, Benjamin, Duffy, Darragh, Quintana-Murci, Llui, van de Beek, Diederik, Roussel, Lucie, Vinh, Donald C, Tangye, Stuart G, Haerynck, Filomeen, Dalmau, David, Martinez-Picado, Javier, Brodin, Petter, Nussenzweig, Michel C, Boisson-Dupuis, Stéphanie, Rodríguez-Gallego, Carlo, Vogt, Guillaume, Mogensen, Trine H, Oler, Andrew J, Gu, Jingwen, Burbelo, Peter D, Cohen, Jeffrey, Biondi, Andrea, Bettini, Laura Rachele, D'Angio, Mariella, Bonfanti, Paolo, Rossignol, Patrick, Mayaux, Julien, Rieux-Laucat, Frédéric, Husebye, Eystein S, Fusco, Francesca, Ursini, Matilde Valeria, Imberti, Luisa, Sottini, Alessandra, Paghera, Simone, Quiros-Roldan, Eugenia, Rossi, Camillo, Castagnoli, Riccardo, Montagna, Daniela, Licari, Amelia, Marseglia, Gian Luigi, Duval, Xavier, Ghosn, Jade, Tsang, John S, Goldbach-Mansky, Raphaela, Kisand, Kai, Lionakis, Michail S, Puel, Anne, Zhang, Shen-Ying, Holland, Steven M, Gorochov, Guy, Jouanguy, Emmanuelle, Rice, Charles M, Cobat, Aurélie, Notarangelo, Luigi D, Abel, Laurent, Su, Helen C, Casanova, Jean-Laurent, Meyts, Isabelle, Bastard, P, Rosen, L, Zhang, Q, Michailidis, E, Hoffmann, H, Zhang, Y, Dorgham, K, Philippot, Q, Rosain, J, Beziat, V, Manry, J, Shaw, E, 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Leo, Y, Lopez, R, Leung, D, Levin, M, Levy, M, Levy, R, Li, Z, Linglart, A, Lorenzo-Salazar, J, Louapre, C, Lubetzki, C, Luyt, C, Lye, D, Mansouri, D, Marjani, M, Pereira, J, Martin, A, Pueyo, D, Marzana, I, Mathian, A, Matos, L, Matthews, G, Mege, J, Melki, I, Meritet, J, Metin, O, Meyts, I, Mezidi, M, Migeotte, I, Millereux, M, Mirault, T, Mircher, C, Mirsaeidi, M, Melian, A, Martinez, A, Morange, P, Mordacq, C, Morelle, G, Mouly, S, Munoz-Barrera, A, Nafati, C, Neves, J, Ng, L, Medina, Y, Cuadros, E, Gonzalo Ocejo-Vinyals, J, Orbak, Z, Oualha, M, Ozcelik, T, Hammarstrom, Q, Parizot, C, Pascreau, T, Paz-Artal, E, de Diego, R, Philippe, A, Philippota, Q, Planas-Serra, L, Ploin, D, Poissy, J, Poncelet, G, Pouletty, M, Quentric, P, Raoult, D, Rebillat, A, Reisli, I, Ricart, P, Richard, J, Rivet, N, Riviere, J, Blanch, G, Rodrigo, C, Rodriguez-Palmero, A, Romero, C, Rothenbuhler, A, Rozenberg, F, del Prado, M, Riera, J, Sanchez, O, Sanchez-Ramon, S, Schluter, A, Schmidt, M, Schweitzer, C, Scolari, F, Sediva, A, Seijo, L, Sene, D, Senoglu, S, Seppanen, M, Ilovich, A, Shahrooei, M, Sobh, A, Moreno, X, Sole-Violan, J, Soler, C, Soler-Palacin, P, Stepanovskiy, Y, Stoclin, A, Taccone, F, Tandjaoui-Lambiottea, Y, Taupin, J, Tavernier, S, Thumerelle, C, Tomasoni, G, Toubiana, J, Alvarez, J, Trouillet-Assanta, S, Troya, J, Tucci, A, Uzunhan, Y, Vabres, P, Valencia-Ramos, J, van Den Rym, A, Vandernoot, I, Vatansev, H, Velez-Santamaria, V, Viel, S, Vilain, C, Vilaire, M, Vincent, A, Voiriot, G, Vuotto, F, Yosunkaya, A, Young, B, Yucel, F, Zannad, F, Zatz, M, Belota, A, Foti, G, Bellani, G, Citerio, G, Contro, E, Pesci, A, Valsecchi, M, Cazzaniga, M, Bole-Feysot, C, Lyonnet, S, Masson, C, Nitschke, P, Pouliet, A, Schmitt, Y, Tores, F, Zarhrate, M, Abela, L, Andrejak, C, Angoulvant, F, Bachelet, D, Basmaci, R, Behillil, S, Beluze, M, Benkerrou, D, Bhavsar, K, Bompart, F, Bouadma, L, Bouscambert, M, Caralp, M, Cervantes-Gonzalez, M, Chair, A, Coelho, A, Couffignal, C, Couffin-Cadiergues, S, D'Ortenzio, E, da Silveira, C, Debray, M, Deplanque, D, Descamps, D, Desvallees, M, Diallo, A, Diouf, A, Dorival, C, Dubos, F, Eloy, P, Enouf, V, Esperou, H, Esposito-Farese, M, Etienne, M, Ettalhaoui, N, Gault, N, Gaymard, A, Gigante, T, Gorenne, I, Guedj, J, Hoctin, A, Hoffmann, I, Jaafoura, S, Kafif, O, Kaguelidou, F, Kali, S, Khalil, A, Khan, C, Laouenan, C, Laribi, S, Le, M, Le Hingrat, Q, Le Mestre, S, Le Nagard, H, Lescure, F, Levy, Y, Levy-Marchal, C, Lina, B, Lingas, G, Lucet, J, Malvy, D, Mambert, M, Mentre, F, Mercier, N, Meziane, A, Mouquet, H, Mullaert, J, Neant, N, Noret, M, Pages, J, Papadopoulos, A, Paul, C, Peiffer-Smadja, N, Petrov-Sanchez, V, Peytavin, G, Picone, O, Puechal, O, Rosa-Calatrava, M, Rossignol, B, Roy, C, Schneider, M, Semaille, C, Mohammed, N, Tagherset, L, Tardivon, C, Tellier, M, Teoule, F, Terrier, O, Timsit, J, Treoux, T, Tual, C, Tubiana, S, van der Werf, S, Vanel, N, Veislinger, A, Visseaux, B, Wiedemann, A, Yazdanpanah, Y, Abelc, L, Alcover, A, Aschard, H, Astrom, K, Bousso, P, Bruhns, P, Cumano, A, Demangel, C, Deriano, L, Santo, J, Dromer, F, Eberl, G, Enninga, J, Fellay, J, Gomperts-Boneca, I, Hasan, M, Hercberg, S, Lantz, O, Patin, E, Pellegrini, S, Pol, S, Rausell, A, Rogge, L, Sakuntabhai, A, Schwartz, O, Schwikowski, B, Shorte, S, Tangy, F, Toubert, A, Touvier, M, Ungeheuer, M, Albert, M, Alavoine, L, Amat, K, Bielicki, J, Bruijning, P, Burdet, C, Caumes, E, Charpentier, C, Coignard, B, Costa, Y, Damond, F, Dechanet, A, Delmas, C, Ecobichon, J, Frezouls, W, Houhou, N, Ilic-Habensus, E, Kikoine, J, Lebeaux, D, Leclercq, A, Lehacaut, J, Letrou, S, Manchon, P, Mandic, M, Meghadecha, M, Motiejunaite, J, Nouroudine, M, Piquard, V, Postolache, A, Quintin, C, Rexach, J, Roufai, L, Terzian, Z, Thy, M, Vignali, V, van Agtmael, M, Algera, A, van Baarle, F, Bax, D, Beudel, M, Bogaard, H, Bomers, M, Bos, L, Botta, M, de Brabander, J, Bree, G, Brouwer, M, de Bruin, S, Bugiani, M, Bulle, E, Chouchane, O, Cloherty, A, Elbers, P, Fleuren, L, Geerlings, S, Geerts, B, Geijtenbeek, T, Girbes, A, Goorhuis, B, Grobusch, M, Hafkamp, F, Hagens, L, Hamann, J, Harris, V, Hemke, R, Hermans, S, Heunks, L, Hollmann, M, Horn, J, Hovius, J, de Jong, M, Koning, R, van Mourik, N, Nellen, J, Paulus, F, Peters, E, van der Poll, T, Preckel, B, Prins, J, Raasveld, J, Reijnders, T, Schinkel, M, Schultz, M, Schuurman, A, Sigaloff, K, Smit, M, Stijnis, C, Stilma, W, Teunissen, C, Thoral, P, Tsonas, A, van der Valk, M, Veelo, D, Vlaar, A, de Vries, H, van Vugt, M, Joost Wiersinga, W, Wouters, D, Zwinderman, A, Abelb, L, Iuti, F, Muhsen, S, Al-Mulla, F, Anderson, M, Bogunovic, D, Bondarenko, A, Bryceson, Y, Bustamante, C, Butte, M, Chakravorty, S, Christodoulou, J, Cirulli, E, Condino-Neto, A, Cooper, M, Derisi, J, Desai, M, Drolet, B, Espinosa, S, Franco, J, Gregersen, P, Hagin, D, Heath, J, Henrickson, S, Hsieh, E, Imai, K, Itan, Y, Karamitros, T, Kisanda, K, Ku, C, Ling, Y, Lucas, C, Maniatis, T, Marodi, L, Milner, J, Mironska, K, Morio, T, Notarangeloa, L, Novelli, G, Novelli, A, O'Farrelly, C, Okada, S, Planas, A, Prando, C, Pujol, A, Renia, L, Renieri, A, Sancho-Shimizu, V, Sankaran, V, Barrett, K, Turvey, S, Uddin, F, Uddin, M, Vazquez, S, von Bernuth, H, Washington, N, Zawadzki, P, Sua, H, Casanovaa, J, Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Rockefeller University [New York], National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Tartu, Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de référence des rhumatismes inflammatoires et maladies auto-immunes systémiques rares de l’enfant / National Referee Centre for Rheumatic and AutoImmune and Systemic Diseases in Children [Lyon] (RAISE), Lyon Immunopathology Federation (LIFe), Tartu University Hospital [Tartu, Estonia], Hôpital Foch [Suresnes], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), UFR SMBH-Université Sorbonne Paris Nord, Helix [San Mateo, CA], University Medical Center [Utrecht], IRCCS Ospedale San Raffaele [Milan, Italy], Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Yale University School of Medicine, Innovations thérapeutiques en hémostase (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163), Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université de Paris (UP), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris], Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Chaire Génomique humaine et évolution, Collège de France (CdF (institution)), Amsterdam Neuroscience [Pays-Bas], Vrije Universiteit Amsterdam [Amsterdam] (VU)-University of Amsterdam [Amsterdam] (UvA)-VU University Medical Center [Amsterdam], McGill University Health Center [Montreal] (MUHC), Garvan Institute of Medical Research [Darlinghurst, Australia], University of New South Wales [Sydney] (UNSW), Ghent University Hospital, Hospital Universitario Mutua de Terrassa, Universitat de Barcelona (UB), Institut d’Investigació Germans Trias i Pujol = Germans Trias i Pujol Research Institute (IGTP), Universitat de Vic-Universitat Central de Catalunya, España, Institució Catalana de Recerca i Estudis Avançats (ICREA), Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Howard Hughes Medical Institute [New York] (HHMI), Howard Hughes Medical Institute (HHMI)-New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC), Hospital Universitario de Gran Canaria Dr Negrin, University Fernando Pessoa - UFP, Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Aarhus University Hospital, Aarhus University [Aarhus], Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Fondazione MBBM-Ospedale [Monza, Italie], San Gerardo Hospital, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Bergen (UiB), Haukeland University Hospital, Consiglio Nazionale delle Ricerche [Napoli] (CNR), Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia [Brescia], Università degli Studi di Brescia [Brescia], Università degli Studi di Pavia, Fondazione IRCCS Policlinico San Matteo, CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Université de Paris - UFR Médecine Paris Nord [Santé] (UP Médecine Paris Nord), Service d'Immunologie [CHU Pitié-Salpétrière], Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), UM1 HG006504/HG/NHGRI NIH HHS/United States, P01 AI138938/AI/NIAID NIH HHS/United States, U19 AI111825/AI/NIAID NIH HHS/United States, U24 HG008956/HG/NHGRI NIH HHS/United States, MR/S032304/1/MRC_/Medical Research Council/United Kingdom, UKRI Future Leader's Fellowship, The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, The Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, the Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the French National Research Agency (ANR) under the Investments for the Future program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project (ANRS-COV05), the Square Foundation, Grandir – Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, the Institut Institut National de la Santé et de la Recherche Médicale (INSERM), and the University of Paris. Samples from San Raffaele Hospital were obtained through the Covid-BioB project and by healthcare personnel of San Raffaele Hospital, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) clinical laboratory and clinical research unit, funded by the Program Project COVID-19 OSR-UniSR and Fondazione Telethon. The French COVID Cohort Study Group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). The Milieu Intérieur Consortium was supported by the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence Milieu Intérieur grant (ANR-10-LABX-69-01) (primary investigators: L.Q.-M. and D.Du.). The Simoa experiment was supported by the PHRC-20-0375 COVID-19 grant 'DIGITAL COVID' (primary investigator: G.G.). S.G.T. is supported by a Leadership 3 Investigator Grant awarded by the National Health and Medical Research Council of Australia and a COVID19 Rapid Response Grant awarded by UNSW Sydney. C.R.-G. and colleagues were supported by the Instituto de Salud Carlos III (COV20_01333 and COV20_01334, Spanish Ministry of Science and Innovation RTC-2017-6471-1, AEI/FEDER, UE) and Cabildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19'). S.T.-A. and A.B. were supported by ANR-20-COVI-0064 (primary investigator: A.Be.). This work is supported by the French Ministry of Health 'Programme Hospitalier de Recherche Clinique Inter regional 2013,' by the Contrat de Plan Etat-Lorraine and FEDER Lorraine, and by a public grant overseen by the French National Research Agency (ANR) as part of the second Investissements d’Avenir program FIGHT-HF (reference no. ANR-15-RHU-0004) and by the French PIA project 'Lorraine Université d’Excellence' (reference no. ANR-15-IDEX-04-LUE) (45), and biobanking is performed by the Biological Resource Center Lorrain BB-0033-00035. This study was supported by the Fonds IMMUNOV, for Innovation in Immunopathology, by a grant from the Agence National de la Recherche (ANR-flash Covid19 'AIROCovid' to F.R.-L.), and by the FAST Foundation (French Friends of Sheba Tel Hashomer Hospital). Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1, a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The Amsterdam UMC Covid-19 Biobank was supported by grants from the Amsterdam Corona Research Fund, the Dr. C.J. Vaillant Fund, and the Netherlands Organization for Health Research and Development [ZonMw, NWO-Vici-Grant (grant no. 918·19·627 to D.v.d.B.)]. This work was also supported by the Division of Intramural Research of the National Institute of Dental Craniofacial Research and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by Regione Lombardia, Italy (project 'Risposta immune in pazienti con COVID-19 e comorbidita'). The opinions and assertions expressed herein are those of the author(s) and do not necessarily reflect the official policy or position of the Uniformed Services University or the Department of Defense. J.H. holds an Institut Imagine M.D.-Ph.D. fellowship from the Fondation Bettencourt Schueller. J.R. is supported by the INSERM Ph.D. program ('poste d’accueil Inserm'). P.Ba. was supported by the French Foundation for Medical Research (FRM, EA20170638020) and the M.D.-Ph.D. program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). We thank the Association 'Turner et vous' for their help and support. Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. D.C.V. is supported by the Fonds de la recherche en santé du Québec clinician-scientist scholar program. K.K. was supported by the Estonian Research Council grant PUT1367. We thank the GEN-COVID Multicenter Study (https://sites.google.com/dbm.unisi.it/gen-covid). We thank the NIAID Office of Cyber Infrastructure and Computational Biology, Bioinformatics and Computational Biosciences Branch (contract no. HHSN316201300006W/HHSN27200002 to MSC, Inc.), the Operations Engineering Branch for developing the HGRepo system to enable streamlined access to the data, and the NCI Advanced Biomedical Computational Science (ABCS) for data transformation support. Biomedical Advanced Research and Development Authority was supported under contract no. HHSO10201600031C (to J.H.). Financial support was provided by the National Institute of Allergy and Infectious Diseases (NIAID) K08AI135091, the Burroughs Wellcome Fund CAMS, the Clinical Immunology Society, and the American Academy of Allergy, Asthma, and Immunology, We thank the patients, their families, and healthy donors for placing their trust in us. We thank the French Incontinentia pigmenti association for their help and support. We thank Y. Nemirovskaya, D. Papandrea, M. Woollett, D. Liu, C. Rivalain, and C. Patissier for administrative assistance, D. Kapogiannis (National Institute on Aging) for providing healthy donor samples, and S. Xirasager, J. Barnett, X. Cheng, S. Weber, J. Danielson, B. Garabedian, and H. Matthews for their assistance in this study. We also thank R. Apps, B. Ryan, and Y. Belkaid of the CHI for their assistance. We thank the CRB-Institut Jérôme Lejeune, CRB-BioJeL, Paris, France, for their assistance. We thank M. C. García Guerrero, I. Erkizia, E. Grau, M. Massanella from IrsiCaixa AIDS Research Institute, Badalona, Spain, and J. Guitart from the Department of Clinical Genetics, University Hospital Germans Trias i Pujol, Badalona, Spain, for providing samples. We also thank J. Dalmau from IrsiCaixa for assistance, HGID Lab, NIAID-USUHS Immune Response to COVID Group, COVID Clinicians, COVID-STORM Clinicians, Imagine COVID Group, French COVID Cohort Study Group, The Milieu Intérieur Consortium, CoV-Contact Cohort, Amsterdam UMC Covid-19 Biobank, COVID Human Genetic, CoV-Contact Cohort: Loubna Alavoine, Karine K. A. Amat, Sylvie Behillil, Julia Bielicki, Patricia Bruijning, Charles Burdet, Eric Caumes, Charlotte Charpentier, Bruno Coignard, Yolande Costa, Sandrine Couffin-Cadiergues, Florence Damond, Aline Dechanet, Christelle Delmas, Diane Descamps, Xavier Duval, Jean-Luc Ecobichon, Vincent Enouf, Hélène Espérou, Wahiba Frezouls, Nadhira Houhou, Emila Ilic-Habensus, Ouifiya Kafif, John Kikoine, Quentin Le Hingrat, David Lebeaux, Anne Leclercq, Jonathan Lehacaut, Sophie Letrou, Bruno Lina, Jean-Christophe Lucet, Denis Malvy, Pauline Manchon, Milica Mandic, Mohamed Meghadecha, Justina Motiejunaite, Mariama Nouroudine, Valentine Piquard, Andreea Postolache, Caroline Quintin, Jade Rexach, Layidé Roufai, Zaven Terzian, Michael Thy, Sarah Tubiana, Sylvie van der Werf, Valérie Vignali, Benoit Visseaux, Yazdan Yazdanpanah, COVID Human Genetic Effort: Laurent Abel, Alessandro Aiuti, Saleh Al Muhsen, Fahd Al-Mulla, Mark S. Anderson, Andrés Augusto Arias, Hagit Baris Feldman, Dusan Bogunovic, Alexandre Bolze, Anastasiia Bondarenko, Ahmed A. Bousfiha, Petter Brodin, Yenan Bryceson, Carlos D. Bustamante, Manish Butte, Giorgio Casari, Samya Chakravorty, John Christodoulou, Elizabeth Cirulli, Antonio Condino-Neto, Megan A. Cooper, Clifton L. Dalgard, Joseph L. DeRisi, Murkesh Desai, Beth A. Drolet, Sara Espinosa, Jacques Fellay, Carlos Flores, Jose Luis Franco, Peter K. Gregersen, Filomeen Haerynck, David Hagin, Rabih Halwani, Jim Heath, Sarah E. Henrickson, Elena Hsieh, Kohsuke Imai, Yuval Itan, Timokratis Karamitros, Kai Kisand, Cheng-Lung Ku, Yu-Lung Lau, Yun Ling, Carrie L. Lucas, Tom Maniatis, Davoud Mansouri, Laszlo Marodi, Isabelle Meyts, Joshua D. Milner, Kristina Mironska, Trine Mogensen, Tomohiro Morio, Lisa F. P. Ng, Luigi D. Notarangelo, Giuseppe Novelli, Antonio Novelli, Cliona O'Farrelly, Satoshi Okada, Tayfun Ozcelik, Rebeca Perez de Diego, Anna M. Planas, Carolina Prando, Aurora Pujol, Lluis Quintana-Murci, Laurent Renia, Alessandra Renieri, Carlos Rodríguez-Gallego, Vanessa Sancho-Shimizu, Vijay Sankaran, Kelly Schiabor Barrett, Mohammed Shahrooei, Andrew Snow, Pere Soler-Palacín, András N. Spaan, Stuart Tangye, Stuart Turvey, Furkan Uddin, Mohammed J. Uddin, Diederik van de Beek, Sara E. Vazquez, Donald C. Vinh, Horst von Bernuth, Nicole Washington, Pawel Zawadzki, Helen C. Su, Jean-Laurent Casanova, Amsterdam UMC Covid-19 Biobank: Michiel van Agtmael, Anna Geke Algera, Frank van Baarle, Diane Bax, Martijn Beudel, Harm Jan Bogaard, Marije Bomers, Lieuwe Bos, Michela Botta, Justin de Brabander, Godelieve Bree, Matthijs C. Brouwer, Sanne de Bruin, Marianna Bugiani, Esther Bulle, Osoul Chouchane, Alex Cloherty, Paul Elbers, Lucas Fleuren, Suzanne Geerlings, Bart Geerts, Theo Geijtenbeek, Armand Girbes, Bram Goorhuis, Martin P. Grobusch, Florianne Hafkamp, Laura Hagens, Jorg Hamann, Vanessa Harris, Robert Hemke, Sabine M. Hermans, Leo Heunks, Markus W. Hollmann, Janneke Horn, Joppe W. Hovius, Menno D. de Jong, Rutger Koning, Niels van Mourik, Jeaninne Nellen, Frederique Paulus, Edgar Peters, Tom van der Poll, Benedikt Preckel, Jan M. Prins, Jorinde Raasveld, Tom Reijnders, Michiel Schinkel, Marcus J. Schultz, Alex Schuurman, Kim Sigaloff, Marry Smit, Cornelis S. Stijnis, Willemke Stilma, Charlotte Teunissen, Patrick Thoral, Anissa Tsonas, Marc van der Valk, Denise Veelo, Alexander P. J. Vlaar, Heder de Vries, Michèle van Vugt, W. Joost Wiersinga, Dorien Wouters, A. H. (Koos) Zwinderman, Diederik van de Beek, HGID Lab: Andrés Augusto Arias, Bertrand Boisson, Soraya Boucherit, Jacinta Bustamante, Marwa Chbihi, Jie Chen, Maya Chrabieh, Tatiana Kochetkov, Tom Le Voyer, Dana Liu, Yelena Nemirovskaya, Masato Ogishi, Dominick Papandrea, Cécile Patissier, Franck Rapaport, Manon Roynard, Natasha Vladikine, Mark Woollett, Peng Zhang, NIAID-USUHS Immune Response to COVID Group: Anuj Kashyap, Li Ding, Marita Bosticardo, Qinlu Wang, Sebastian Ochoa, Hui Liu, Samuel D. Chauvin, Michael Stack, Galina Koroleva, Neha Bansal, Clifton L. Dalgard, Andrew L. Snow, COVID Clinicians: Jorge Abad, Sergio Aguilera-Albesa, Ozge Metin Akcan, Ilad Alavi Darazam, Juan C. Aldave, Miquel Alfonso Ramos, Seyed Alireza Nadji, Gulsum Alkan, Jerome Allardet-Servent, Luis M. Allende, Laia Alsina, Marie-Alexandra Alyanakian, Blanca Amador-Borrero, Zahir Amoura, Arnau Antolí, Sevket Arslan, Sophie Assant, Terese Auguet, Axelle Azot, Fanny Bajolle, Aurélie Baldolli, Maite Ballester, Hagit Baris Feldman, Benoit Barrou, Alexandra Beurton, Agurtzane Bilbao, Geraldine Blanchard-Rohner, Ignacio Blanco, Adeline Blandinières, Daniel Blazquez-Gamero, Marketa Bloomfield, Mireia Bolivar-Prados, Raphael Borie, Ahmed A. Bousfiha, Claire Bouvattier, Oksana Boyarchuk, Maria Rita P. Bueno, Jacinta Bustamante, Juan José Cáceres Agra, Semra Calimli, Ruggero Capra, Maria Carrabba, Carlos Casasnovas, Marion Caseris, Martin Castelle, Francesco Castelli, Martín Castillo de Vera, Mateus V. Castro, Emilie Catherinot, Martin Chalumeau, Bruno Charbit, Matthew P. Cheng, Père Clavé, Bonaventura Clotet, Anna Codina, Fatih Colkesen, Fatma Colkesen, Roger Colobran, Cloé Comarmond, Angelo G. Corsico, David Dalmau, David Ross Darley, Nicolas Dauby, Stéphane Dauger, Loic de Pontual, Amin Dehban, Geoffroy Delplancq, Alexandre Demoule, Antonio Di Sabatino, Jean-Luc Diehl, Stephanie Dobbelaere, Sophie Durand, Waleed Eldars, Mohamed Elgamal, Marwa H. Elnagdy, Melike Emiroglu, Emine Hafize Erdeniz, Selma Erol Aytekin, Romain Euvrard, Recep Evcen, Giovanna Fabio, Laurence Faivre, Antonin Falck, Muriel Fartoukh, Morgane Faure, Miguel Fernandez Arquero, Carlos Flores, Bruno Francois, Victoria Fumadó, Francesca Fusco, Blanca Garcia Solis, Pascale Gaussem, Juana Gil-Herrera, Laurent Gilardin, Monica Girona Alarcon, Mónica Girona-Alarcón, Jean-Christophe Goffard, Funda Gok, Rafaela González-Montelongo, Antoine Guerder, Yahya Gul, Sukru Nail Guner, Marta Gut, Jérôme Hadjadj, Filomeen Haerynck, Rabih Halwani, Lennart Hammarström, Nevin Hatipoglu, Elisa Hernandez-Brito, María Soledad Holanda-Peña, Juan Pablo Horcajada, Sami Hraiech, Linda Humbert, Alejandro D. Iglesias, Antonio Íñigo-Campos, Matthieu Jamme, María Jesús Arranz, Iolanda Jordan, Fikret Kanat, Hasan Kapakli, Iskender Kara, Adem Karbuz, Kadriye Kart Yasar, Sevgi Keles, Yasemin Kendir Demirkol, Adam Klocperk, Zbigniew J. Król, Paul Kuentz, Yat Wah M. Kwan, Jean-Christophe Lagier, Yu-Lung Lau, Fleur Le Bourgeois, Yee-Sin Leo, Rafael Leon Lopez, Daniel Leung, Michael Levin, Michael Levy, Romain Lévy, Zhi Li, Agnes Linglart, José M. Lorenzo-Salazar, Céline Louapre, Catherine Lubetzki, Charles-Edouard Luyt, David C. Lye, Davood Mansouri, Majid Marjani, Jesus Marquez Pereira, Andrea Martin, David Martínez Pueyo, Javier Martinez-Picado, Iciar Marzana, Alexis Mathian, Larissa R. B. Matos, Gail V. Matthews, Julien Mayaux, Jean-Louis Mège, Isabelle Melki, Jean-François Meritet, Ozge Metin, Isabelle Meyts, Mehdi Mezidi, Isabelle Migeotte, Maude Millereux, Tristan Mirault, Clotilde Mircher, Mehdi Mirsaeidi, Abián Montesdeoca Melián, Antonio Morales Martinez, Pierre Morange, Clémence Mordacq, Guillaume Morelle, Stéphane Mouly, Adrián Muñoz-Barrera, Cyril Nafati, João Farela Neves, Lisa F. P. Ng Yeray Novoa Medina, Esmeralda Nuñez Cuadros, J. Gonzalo Ocejo-Vinyals, Zerrin Orbak, Mehdi Oualha, Tayfun Özçelik, Qiang Pan Hammarström, Christophe Parizot, Tiffany Pascreau, Estela Paz-Artal, Rebeca Pérez de Diego, Aurélien Philippe, Quentin Philippot, Laura Planas-Serra, Dominique Ploin, Julien Poissy, Géraldine Poncelet, Marie Pouletty, Paul Quentric, Didier Raoult, Anne-Sophie Rebillat, Ismail Reisli, Pilar Ricart, Jean-Christophe Richard, Nadia Rivet, Jacques G. Rivière, Gemma Rocamora Blanch, Carlos Rodrigo, Carlos Rodriguez-Gallego, Agustí Rodríguez-Palmero, Carolina Soledad Romero, Anya Rothenbuhler, Flore Rozenberg, Maria Yolanda Ruiz del Prado, Joan Sabater Riera, Oliver Sanchez, Silvia Sánchez-Ramón, Agatha Schluter, Matthieu Schmidt, Cyril E. Schweitzer, Francesco Scolari, Anna Sediva, Luis M. Seijo, Damien Sene, Sevtap Senoglu, Mikko R. J. Seppänen, Alex Serra Ilovich, Mohammad Shahrooei, David Smadja, Ali Sobh, Xavier Solanich Moreno, Jordi Solé-Violán, Catherine Soler, Pere Soler-Palacín, Yuri Stepanovskiy, Annabelle Stoclin, Fabio Taccone, Yacine Tandjaoui-Lambiotte, Jean-Luc Taupin, Simon J. Tavernier, Benjamin Terrier, Caroline Thumerelle, Gabriele Tomasoni, Julie Toubiana, Josep Trenado Alvarez, Sophie Trouillet-Assant, Jesús Troya, Alessandra Tucci, Matilde Valeria Ursini‬, Yurdagul Uzunhan, Pierre Vabres, Juan Valencia-Ramos, Ana Maria Van Den Rym, Isabelle Vandernoot, Hulya Vatansev, Valentina Vélez-Santamaria, Sébastien Viel, Cédric Vilain, Marie E. Vilaire, Audrey Vincent, Guillaume Voiriot, Fanny Vuotto, Alper Yosunkaya, Barnaby E. Young, Fatih Yucel, Faiez Zannad, Mayana Zatz, Alexandre Belot, COVID-STORM Clinicians: Giuseppe Foti, Giacomo Bellani, Giuseppe Citerio, Ernesto Contro, Alberto Pesci, Maria Grazia Valsecchi, Marina Cazzaniga, Imagine COVID Group: Christine Bole-Feysot, Stanislas Lyonnet, Cécile Masson, Patrick Nitschke, Aurore Pouliet, Yoann Schmitt, Frederic Tores, Mohammed Zarhrate, French COVID Cohort Study Group: Laurent Abel, Claire Andrejak, François Angoulvant, Delphine Bachelet, Romain Basmaci, Sylvie Behillil, Marine Beluze, Dehbia Benkerrou, Krishna Bhavsar, François Bompart, Lila Bouadma, Maude Bouscambert, Mireille Caralp, Minerva Cervantes-Gonzalez, Anissa Chair, Alexandra Coelho, Camille Couffignal, Sandrine Couffin-Cadiergues, Eric D’ortenzio, Charlene Da Silveira, Marie-Pierre Debray, Dominique Deplanque, Diane Descamps, Mathilde Desvallées, Alpha Diallo, Alphonsine Diouf, Céline Dorival, François Dubos, Xavier Duval, Philippine Eloy, Vincent V. E. Enouf, Hélène Esperou, Marina Esposito-Farese, Manuel Etienne, Nadia Ettalhaoui, Nathalie Gault, Alexandre Gaymard, Jade Ghosn, Tristan Gigante, Isabelle Gorenne, Jérémie Guedj, Alexandre Hoctin, Isabelle Hoffmann, Salma Jaafoura, Ouifiya Kafif, Florentia Kaguelidou, Sabina Kali, Antoine Khalil, Coralie Khan, Cédric Laouénan, Samira Laribi, Minh Le, Quentin Le Hingrat, Soizic Le Mestre, Hervé Le Nagard, François-Xavier Lescure, Yves Lévy, Claire Levy-Marchal, Bruno Lina, Guillaume Lingas, Jean Christophe Lucet, Denis Malvy, Marina Mambert, France Mentré, Noémie Mercier, Amina Meziane, Hugo Mouquet, Jimmy Mullaert, Nadège Neant, Marion Noret, Justine Pages, Aurélie Papadopoulos, Christelle Paul, Nathan Peiffer-Smadj, Ventzislava Petrov-Sanchez, Gilles Peytavin, Olivier Picone, Oriane Puéchal, Manuel Rosa-Calatrava, Bénédicte Rossignol, Patrick Rossignol, Carine Roy, Marion Schneider, Caroline Semaille, Nassima Si Mohammed, Lysa Tagherset, Coralie Tardivon, Marie-Capucine Tellier, François Téoulé, Olivier Terrier, Jean-François Timsit, Théo Treoux, Christelle Tual, Sarah Tubiana, Sylvie van der Werf, Noémie Vanel, Aurélie Veislinger, Benoit Visseaux, Aurélie Wiedemann, Yazdan Yazdanpanan, The Milieu Intérieur Consortium: Laurent Abel, Andres Alcover, Hugues Aschard, Kalla Astrom, Philippe Bousso, Pierre Bruhns, Ana Cumano, Caroline Demangel, Ludovic Deriano, James Di Santo, Françoise Dromer, Gérard Eberl, Jost Enninga, Jacques Fellay, Ivo Gomperts-Boneca, Milena Hasan, Serge Hercberg, Olivier Lantz, Hugo Mouquet, Etienne Patin, Sandra Pellegrini, Stanislas Pol, Antonio Rausell, Lars Rogge, Anavaj Sakuntabhai, Olivier Schwartz, Benno Schwikowski, Spencer Shorte, Frédéric Tangy, Antoine Toubert, Mathilde Touvier, Marie-Noëlle Ungeheuer, Matthew L. Albert, Darragh Duffy, Lluis Quintana-Murci, ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0003,GENCOVID,Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé(2020), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), ANR-20-COVI-0064,IFN-COVID19,Etude de la régulation de la réponse interferon de type I dans le control de l'infection par SARS-Cov2 et sa pathogènese(2020), ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE,Isite LUE(2015), ANR-20-COVI-0022,AIROCovid19,Analyse Omics de la réponse immune aigue au cours de l'infection à Covid19: rationnel moléculaire pour un traitement ciblé(2020), Howard Hughes Medical Institute, Rockefeller University, National Institutes of Health (US), National Center for Advancing Translational Sciences (US), George Mason University, National Human Genome Research Institute (US), Agence Nationale de la Recherche (France), Fondation pour la Recherche Médicale, Pershing Square Foundation, Institut National de la Santé et de la Recherche Médicale (France), Université de Paris, Fondazione Telethon, Ministère des Solidarités et de la Santé (France), European Commission, National Health and Medical Research Council (Australia), University of New South Wales (Australia), Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Cabildo de Tenerife, Fondation Bettencourt Schueller, Estonian Research Council, Rosen, Lindsey B., Michailidis, Eleftherios, Haljasmägi, Liis, Spaan, András N., Quintana-Murci, Lluis, Beek, Diederik van der, Vinh, Donald C., Tangye, Stuart G., Martínez-Picado, Javier, Brodin, Peter, Nussenzweig, Michel C., Rodríguez-Gallego, Carlos, Mogensen, Trine, Oler, Andrew J., Burbelo, Peter D., Husebye, Eystein S., Children's Hospital, HUS Children and Adolescents, Clinicum, Department of Medicine, Neurology, AII - Infectious diseases, ANS - Neuroinfection & -inflammation, Infectious diseases, ACS - Pulmonary hypertension & thrombosis, Intensive Care Medicine, ACS - Microcirculation, ACS - Heart failure & arrhythmias, Anesthesiology, ACS - Diabetes & metabolism, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Yale School of Medicine [New Haven, Connecticut] (YSM), Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Collège de France - Chaire Génomique humaine et évolution, Garvan Institute of medical research, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), San Gerardo Hospital of Monza, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Università degli Studi di Brescia = University of Brescia (UniBs), Università degli Studi di Pavia = University of Pavia (UNIPV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Virologie (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and J. Guitart from the Department of Clinical Genetics, University Hospital Germans Trias i Pujol, Badalona, Spain, for providing samples. We also thank J. Dalmau from IrsiCaixa for assistance HGID Lab, NIAID-USUHS Immune Response to COVID Group, COVID Clinicians, COVID-STORM Clinicians, Imagine COVID Group, French COVID Cohort Study Group, The Milieu Intérieur Consortium, CoV-Contact Cohort, Amsterdam UMC Covid-19 Biobank, COVID Human Genetic CoV-Contact Cohort: Loubna Alavoine, Karine K. A. Amat, Sylvie Behillil, Julia Bielicki, Patricia Bruijning, Charles Burdet, Eric Caumes, Charlotte Charpentier, Bruno Coignard, Yolande Costa, Sandrine Couffin-Cadiergues, Florence Damond, Aline Dechanet, Christelle Delmas, Diane Descamps, Xavier Duval, Jean-Luc Ecobichon, Vincent Enouf, Hélène Espérou, Wahiba Frezouls, Nadhira Houhou, Emila Ilic-Habensus, Ouifiya Kafif, John Kikoine, Quentin Le Hingrat, David Lebeaux, Anne Leclercq, Jonathan Lehacaut, Sophie Letrou, Bruno Lina, Jean-Christophe Lucet, Denis Malvy, Pauline Manchon, Milica Mandic, Mohamed Meghadecha, Justina Motiejunaite, Mariama Nouroudine, Valentine Piquard, Andreea Postolache, Caroline Quintin, Jade Rexach, Layidé Roufai, Zaven Terzian, Michael Thy, Sarah Tubiana, Sylvie van der Werf, Valérie Vignali, Benoit Visseaux, Yazdan Yazdanpanah COVID Human Genetic Effort: Laurent Abel, Alessandro Aiuti, Saleh Al Muhsen, Fahd Al-Mulla, Mark S. Anderson, Andrés Augusto Arias, Hagit Baris Feldman, Dusan Bogunovic, Alexandre Bolze, Anastasiia Bondarenko, Ahmed A. Bousfiha, Petter Brodin, Yenan Bryceson, Carlos D. Bustamante, Manish Butte, Giorgio Casari, Samya Chakravorty, John Christodoulou, Elizabeth Cirulli, Antonio Condino-Neto, Megan A. Cooper, Clifton L. Dalgard, Joseph L. DeRisi, Murkesh Desai, Beth A. Drolet, Sara Espinosa, Jacques Fellay, Carlos Flores, Jose Luis Franco, Peter K. Gregersen, Filomeen Haerynck, David Hagin, Rabih Halwani, Jim Heath, Sarah E. Henrickson, Elena Hsieh, Kohsuke Imai, Yuval Itan, Timokratis Karamitros, Kai Kisand, Cheng-Lung Ku, Yu-Lung Lau, Yun Ling, Carrie L. Lucas, Tom Maniatis, Davoud Mansouri, Laszlo Marodi, Isabelle Meyts, Joshua D. Milner, Kristina Mironska, Trine Mogensen, Tomohiro Morio, Lisa F. P. Ng, Luigi D. Notarangelo, Giuseppe Novelli, Antonio Novelli, Cliona O'Farrelly, Satoshi Okada, Tayfun Ozcelik, Rebeca Perez de Diego, Anna M. Planas, Carolina Prando, Aurora Pujol, Lluis Quintana-Murci, Laurent Renia, Alessandra Renieri, Carlos Rodríguez-Gallego, Vanessa Sancho-Shimizu, Vijay Sankaran, Kelly Schiabor Barrett, Mohammed Shahrooei, Andrew Snow, Pere Soler-Palacín, András N. Spaan, Stuart Tangye, Stuart Turvey, Furkan Uddin, Mohammed J. Uddin, Diederik van de Beek, Sara E. Vazquez, Donald C. Vinh, Horst von Bernuth, Nicole Washington, Pawel Zawadzki, Helen C. Su, Jean-Laurent Casanova Amsterdam UMC Covid-19 Biobank: Michiel van Agtmael, Anna Geke Algera, Frank van Baarle, Diane Bax, Martijn Beudel, Harm Jan Bogaard, Marije Bomers, Lieuwe Bos, Michela Botta, Justin de Brabander, Godelieve Bree, Matthijs C. Brouwer, Sanne de Bruin, Marianna Bugiani, Esther Bulle, Osoul Chouchane, Alex Cloherty, Paul Elbers, Lucas Fleuren, Suzanne Geerlings, Bart Geerts, Theo Geijtenbeek, Armand Girbes, Bram Goorhuis, Martin P. Grobusch, Florianne Hafkamp, Laura Hagens, Jorg Hamann, Vanessa Harris, Robert Hemke, Sabine M. Hermans, Leo Heunks, Markus W. Hollmann, Janneke Horn, Joppe W. Hovius, Menno D. de Jong, Rutger Koning, Niels van Mourik, Jeaninne Nellen, Frederique Paulus, Edgar Peters, Tom van der Poll, Benedikt Preckel, Jan M. Prins, Jorinde Raasveld, Tom Reijnders, Michiel Schinkel, Marcus J. Schultz, Alex Schuurman, Kim Sigaloff, Marry Smit, Cornelis S. Stijnis, Willemke Stilma, Charlotte Teunissen, Patrick Thoral, Anissa Tsonas, Marc van der Valk, Denise Veelo, Alexander P. J. Vlaar, Heder de Vries, Michèle van Vugt, W. Joost Wiersinga, Dorien Wouters, A. H. (Koos) Zwinderman, Diederik van de Beek HGID Lab: Andrés Augusto Arias, Bertrand Boisson, Soraya Boucherit, Jacinta Bustamante, Marwa Chbihi, Jie Chen, Maya Chrabieh, Tatiana Kochetkov, Tom Le Voyer, Dana Liu, Yelena Nemirovskaya, Masato Ogishi, Dominick Papandrea, Cécile Patissier, Franck Rapaport, Manon Roynard, Natasha Vladikine, Mark Woollett, Peng Zhang NIAID-USUHS Immune Response to COVID Group: Anuj Kashyap, Li Ding, Marita Bosticardo, Qinlu Wang, Sebastian Ochoa, Hui Liu, Samuel D. Chauvin, Michael Stack, Galina Koroleva, Neha Bansal, Clifton L. Dalgard, Andrew L. Snow COVID Clinicians: Jorge Abad, Sergio Aguilera-Albesa, Ozge Metin Akcan, Ilad Alavi Darazam, Juan C. Aldave, Miquel Alfonso Ramos, Seyed Alireza Nadji, Gulsum Alkan, Jerome Allardet-Servent, Luis M. Allende, Laia Alsina, Marie-Alexandra Alyanakian, Blanca Amador-Borrero, Zahir Amoura, Arnau Antolí, Sevket Arslan, Sophie Assant, Terese Auguet, Axelle Azot, Fanny Bajolle, Aurélie Baldolli, Maite Ballester, Hagit Baris Feldman, Benoit Barrou, Alexandra Beurton, Agurtzane Bilbao, Geraldine Blanchard-Rohner, Ignacio Blanco, Adeline Blandinières, Daniel Blazquez-Gamero, Marketa Bloomfield, Mireia Bolivar-Prados, Raphael Borie, Ahmed A. Bousfiha, Claire Bouvattier, Oksana Boyarchuk, Maria Rita P. Bueno, Jacinta Bustamante, Juan José Cáceres Agra, Semra Calimli, Ruggero Capra, Maria Carrabba, Carlos Casasnovas, Marion Caseris, Martin Castelle, Francesco Castelli, Martín Castillo de Vera, Mateus V. Castro, Emilie Catherinot, Martin Chalumeau, Bruno Charbit, Matthew P. Cheng, Père Clavé, Bonaventura Clotet, Anna Codina, Fatih Colkesen, Fatma Colkesen, Roger Colobran, Cloé Comarmond, Angelo G. Corsico, David Dalmau, David Ross Darley, Nicolas Dauby, Stéphane Dauger, Loic de Pontual, Amin Dehban, Geoffroy Delplancq, Alexandre Demoule, Antonio Di Sabatino, Jean-Luc Diehl, Stephanie Dobbelaere, Sophie Durand, Waleed Eldars, Mohamed Elgamal, Marwa H. Elnagdy, Melike Emiroglu, Emine Hafize Erdeniz, Selma Erol Aytekin, Romain Euvrard, Recep Evcen, Giovanna Fabio, Laurence Faivre, Antonin Falck, Muriel Fartoukh, Morgane Faure, Miguel Fernandez Arquero, Carlos Flores, Bruno Francois, Victoria Fumadó, Francesca Fusco, Blanca Garcia Solis, Pascale Gaussem, Juana Gil-Herrera, Laurent Gilardin, Monica Girona Alarcon, Mónica Girona-Alarcón, Jean-Christophe Goffard, Funda Gok, Rafaela González-Montelongo, Antoine Guerder, Yahya Gul, Sukru Nail Guner, Marta Gut, Jérôme Hadjadj, Filomeen Haerynck, Rabih Halwani, Lennart Hammarström, Nevin Hatipoglu, Elisa Hernandez-Brito, María Soledad Holanda-Peña, Juan Pablo Horcajada, Sami Hraiech, Linda Humbert, Alejandro D. Iglesias, Antonio Íñigo-Campos, Matthieu Jamme, María Jesús Arranz, Iolanda Jordan, Fikret Kanat, Hasan Kapakli, Iskender Kara, Adem Karbuz, Kadriye Kart Yasar, Sevgi Keles, Yasemin Kendir Demirkol, Adam Klocperk, Zbigniew J. Król, Paul Kuentz, Yat Wah M. Kwan, Jean-Christophe Lagier, Yu-Lung Lau, Fleur Le Bourgeois, Yee-Sin Leo, Rafael Leon Lopez, Daniel Leung, Michael Levin, Michael Levy, Romain Lévy, Zhi Li, Agnes Linglart, José M. Lorenzo-Salazar, Céline Louapre, Catherine Lubetzki, Charles-Edouard Luyt, David C. Lye, Davood Mansouri, Majid Marjani, Jesus Marquez Pereira, Andrea Martin, David Martínez Pueyo, Javier Martinez-Picado, Iciar Marzana, Alexis Mathian, Larissa R. B. Matos, Gail V. Matthews, Julien Mayaux, Jean-Louis Mège, Isabelle Melki, Jean-François Meritet, Ozge Metin, Isabelle Meyts, Mehdi Mezidi, Isabelle Migeotte, Maude Millereux, Tristan Mirault, Clotilde Mircher, Mehdi Mirsaeidi, Abián Montesdeoca Melián, Antonio Morales Martinez, Pierre Morange, Clémence Mordacq, Guillaume Morelle, Stéphane Mouly, Adrián Muñoz-Barrera, Cyril Nafati, João Farela Neves, Lisa F. P. Ng Yeray Novoa Medina, Esmeralda Nuñez Cuadros, J. Gonzalo Ocejo-Vinyals, Zerrin Orbak, Mehdi Oualha, Tayfun Özçelik, Qiang Pan Hammarström, Christophe Parizot, Tiffany Pascreau, Estela Paz-Artal, Rebeca Pérez de Diego, Aurélien Philippe, Quentin Philippot, Laura Planas-Serra, Dominique Ploin, Julien Poissy, Géraldine Poncelet, Marie Pouletty, Paul Quentric, Didier Raoult, Anne-Sophie Rebillat, Ismail Reisli, Pilar Ricart, Jean-Christophe Richard, Nadia Rivet, Jacques G. Rivière, Gemma Rocamora Blanch, Carlos Rodrigo, Carlos Rodriguez-Gallego, Agustí Rodríguez-Palmero, Carolina Soledad Romero, Anya Rothenbuhler, Flore Rozenberg, Maria Yolanda Ruiz del Prado, Joan Sabater Riera, Oliver Sanchez, Silvia Sánchez-Ramón, Agatha Schluter, Matthieu Schmidt, Cyril E. Schweitzer, Francesco Scolari, Anna Sediva, Luis M. Seijo, Damien Sene, Sevtap Senoglu, Mikko R. J. Seppänen, Alex Serra Ilovich, Mohammad Shahrooei, David Smadja, Ali Sobh, Xavier Solanich Moreno, Jordi Solé-Violán, Catherine Soler, Pere Soler-Palacín, Yuri Stepanovskiy, Annabelle Stoclin, Fabio Taccone, Yacine Tandjaoui-Lambiotte, Jean-Luc Taupin, Simon J. Tavernier, Benjamin Terrier, Caroline Thumerelle, Gabriele Tomasoni, Julie Toubiana, Josep Trenado Alvarez, Sophie Trouillet-Assant, Jesús Troya, Alessandra Tucci, Matilde Valeria Ursini‬, Yurdagul Uzunhan, Pierre Vabres, Juan Valencia-Ramos, Ana Maria Van Den Rym, Isabelle Vandernoot, Hulya Vatansev, Valentina Vélez-Santamaria, Sébastien Viel, Cédric Vilain, Marie E. Vilaire, Audrey Vincent, Guillaume Voiriot, Fanny Vuotto, Alper Yosunkaya, Barnaby E. Young, Fatih Yucel, Faiez Zannad, Mayana Zatz, Alexandre Belot COVID-STORM Clinicians: Giuseppe Foti, Giacomo Bellani, Giuseppe Citerio, Ernesto Contro, Alberto Pesci, Maria Grazia Valsecchi, Marina Cazzaniga Imagine COVID Group: Christine Bole-Feysot, Stanislas Lyonnet, Cécile Masson, Patrick Nitschke, Aurore Pouliet, Yoann Schmitt, Frederic Tores, Mohammed Zarhrate French COVID Cohort Study Group: Laurent Abel, Claire Andrejak, François Angoulvant, Delphine Bachelet, Romain Basmaci, Sylvie Behillil, Marine Beluze, Dehbia Benkerrou, Krishna Bhavsar, François Bompart, Lila Bouadma, Maude Bouscambert, Mireille Caralp, Minerva Cervantes-Gonzalez, Anissa Chair, Alexandra Coelho, Camille Couffignal, Sandrine Couffin-Cadiergues, Eric D’ortenzio, Charlene Da Silveira, Marie-Pierre Debray, Dominique Deplanque, Diane Descamps, Mathilde Desvallées, Alpha Diallo, Alphonsine Diouf, Céline Dorival, François Dubos, Xavier Duval, Philippine Eloy, Vincent V. E. Enouf, Hélène Esperou, Marina Esposito-Farese, Manuel Etienne, Nadia Ettalhaoui, Nathalie Gault, Alexandre Gaymard, Jade Ghosn, Tristan Gigante, Isabelle Gorenne, Jérémie Guedj, Alexandre Hoctin, Isabelle Hoffmann, Salma Jaafoura, Ouifiya Kafif, Florentia Kaguelidou, Sabina Kali, Antoine Khalil, Coralie Khan, Cédric Laouénan, Samira Laribi, Minh Le, Quentin Le Hingrat, Soizic Le Mestre, Hervé Le Nagard, François-Xavier Lescure, Yves Lévy, Claire Levy-Marchal, Bruno Lina, Guillaume Lingas, Jean Christophe Lucet, Denis Malvy, Marina Mambert, France Mentré, Noémie Mercier, Amina Meziane, Hugo Mouquet, Jimmy Mullaert, Nadège Neant, Marion Noret, Justine Pages, Aurélie Papadopoulos, Christelle Paul, Nathan Peiffer-Smadj, Ventzislava Petrov-Sanchez, Gilles Peytavin, Olivier Picone, Oriane Puéchal, Manuel Rosa-Calatrava, Bénédicte Rossignol, Patrick Rossignol, Carine Roy, Marion Schneider, Caroline Semaille, Nassima Si Mohammed, Lysa Tagherset, Coralie Tardivon, Marie-Capucine Tellier, François Téoulé, Olivier Terrier, Jean-François Timsit, Théo Treoux, Christelle Tual, Sarah Tubiana, Sylvie van der Werf, Noémie Vanel, Aurélie Veislinger, Benoit Visseaux, Aurélie Wiedemann, Yazdan Yazdanpanan The Milieu Intérieur Consortium: Laurent Abel, Andres Alcover, Hugues Aschard, Kalla Astrom, Philippe Bousso, Pierre Bruhns, Ana Cumano, Caroline Demangel, Ludovic Deriano, James Di Santo, Françoise Dromer, Gérard Eberl, Jost Enninga, Jacques Fellay, Ivo Gomperts-Boneca, Milena Hasan, Serge Hercberg, Olivier Lantz, Hugo Mouquet, Etienne Patin, Sandra Pellegrini, Stanislas Pol, Antonio Rausell, Lars Rogge, Anavaj Sakuntabhai, Olivier Schwartz, Benno Schwikowski, Spencer Shorte, Frédéric Tangy, Antoine Toubert, Mathilde Touvier, Marie-Noëlle Ungeheuer, Matthew L. Albert, Darragh Duffy, Lluis Quintana-Murci, Bastard, Paul [0000-0002-5926-8437], Rosen, Lindsey B. [0000-0001-5894-3878], Zhang, Qian [0000-0002-9040-3289], Michailidis, Eleftherios [0000-0002-9907-4346], Dorgham, Karim [0000-0001-9539-3203], Béziat, Vivien [0000-0002-4020-824X], Manry, Jérémy [0000-0001-5998-2051], Shaw, Elana [0000-0001-9265-8026], Haljasmägi, Liis [0000-0001-7162-9808], Peterson, Pärt [0000-0001-6755-791X], Lorenzo, Lazaro [0000-0001-6648-8684], Bizien, Lucy [0000-0001-9163-9122], Trouillet-Assant, Sophie [0000-0001-6439-4705], Dobbs, Kerry [0000-0002-3432-3137], Belot, Alexandre [0000-0003-4902-5332], Kallaste, Anne [0000-0002-7492-667X], Tandjaoui-Lambiotte, Yacine [0000-0003-1123-4788], Le Pen, Jeremie [0000-0001-7025-9526], Kerner, Gaspard [0000-0003-0146-9428], Bigio, Benedetta [0000-0001-7291-5638], Yang, Rui [0000-0003-4427-2158], Bolze, Alexandre [0000-0001-7399-2766], Spaan, András N. [0000-0001-5981-7259], Aiuti, Alessandro [0000-0002-5398-1717], Lampasona, Vito [0000-0001-5162-8445], Piemonti, Lorenzo [0000-0002-2172-2198], Bilguvar, Kaya [0000-0002-7313-7652], Migaud, Mélanie [0000-0003-3062-1214], Hadjadj, Jérome [0000-0002-2520-3272], Terrier, Benjamin [0000-0001-6612-7336], Duffy, Darragh [0000-0002-8875-2308], Quintana-Murci, Lluis [0000-0003-2429-6320], Beek, Diederik van der [0000-0002-4571-044X], Roussel, Lucie [0000-0001-5355-702X], Vinh, Donald C. [0000-0003-1347-7767], Tangye, Stuart G. [0000-0002-5360-5180], Dalmau, David [0000-0003-1936-478X], Martínez-Picado, Javier [0000-0002-4916-2129], Brodin, Peter [0000-0002-8103-0046], Nussenzweig, Michel C. [0000-0003-0592-8564], Boisson-Dupuis, Stéphanie [0000-0002-7115-116X], Rodríguez-Gallego, Carlos [0000-0002-4344-8644], Mogensen, Trine [0000-0002-1853-9704], Oler, Andrew J. [0000-0002-6310-0434], Burbelo, Peter D. [0000-0003-1717-048X], Cohen, Jeffrey [0000-0003-0238-7176], Bettini, Laura Rachele [0000-0002-0280-1704], Bonfanti, Paolo [0000-0001-7289-8823], Rieux-Laucat, Frédéric [0000-0001-7858-7866], Husebye, Eystein S. [0000-0002-7886-2976], Castagnoli, Riccardo [0000-0003-0029-9383], Licari, Amelia [0000-0002-1773-6482], Vougny, Marie-Christine, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Laboratoires d'excellence - GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE - - MILIEU INTERIEUR2010 - ANR-10-LABX-0069 - LABX - VALID, ISITE - Isite LUE - - LUE2015 - ANR-15-IDEX-0004 - IDEX - VALID, Combattre l'insuffisance cardiaque - - FIGHT-HF2015 - ANR-15-RHUS-0004 - RHUS - VALID, Etude de la régulation de la réponse interferon de type I dans le control de l'infection par SARS-Cov2 et sa pathogènese - - IFN-COVID192020 - ANR-20-COVI-0064 - COVID-19 - VALID, Analyse Omics de la réponse immune aigue au cours de l'infection à Covid19: rationnel moléculaire pour un traitement ciblé - - AIROCovid192020 - ANR-20-COVI-0022 - COVID-19 - VALID, Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé - - GENCOVID2020 - ANR-20-COVI-0003 - COVID-19 - VALID, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Howard Hughes Medical Institute (HHMI)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC)-New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'anesthésiologie et soins intensifs [CHU Pitié-Salpêtrière], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Paris Diderot - Paris 7 - UFR Lettres, Arts, Langues, Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Service d'immunologie [CHU Pitié-Salpétrière], Funding: The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the French National Research Agency (ANR) under the 'Investments for the Future' program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project, ANRS-COV05, the Square Foundation, Grandir - Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, Institut Institut National de la Santé et de la Recherche Médicale (INSERM) and the University of Paris. Samples from San Raffaele Hospital were obtained within the Covid-BioB project and healthcare personnel of San Raffaele Hospital, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) clinical lab and clinical research Unit, funded by the Program Project COVID-19 OSR-UniSR and Fondazione Telethon. The French COVID Cohort study group was sponsored by Inserm and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). The 'Milieu Intérieur' cohort was supported by was supported by the French Government’s Investissement d’Avenir Program, Laboratoire d’Excellence 'Milieu Intérieur' Grant (ANR-10-LABX-69-01) (PI: L Quintana-Murci & D Duffy). The Simoa experiment was supported by the PHRC-20-0375 COVID-19 grant 'DIGITAL COVID' (PI: G Gorochov). SGT is supported by a Leadership 3 Investigator Grant awarded by the National Health and Medical Research Council of Australia, and a COVID19 Rapid Response Grant awarded by UNSW Sydney. CRG and colleagues were supported by Instituto de Salud Carlos III (COV20_01333 and COV20_01334, Spanish Ministry of Science and Innovation -RTC-2017-6471-1, AEI/FEDER, UE), and Cabildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19'). SA and AB were supported by ANR-20-COVI-0064 (PI: A Belot). This work is supported by the French Ministry of Health 'Programme Hospitalier de Recherche Clinique Inter regional 2013', by the Contrat de Plan Etat-Lorraine and FEDER Lorraine, and a public grant overseen by the French National Research Agency (ANR) as part of the second 'Investissements d’Avenir' program FIGHT-HF (reference: ANR-15-RHU-0004) and by the French PIA project 'Lorraine Université d’Excellence', reference ANR-15-IDEX-04-LUE (45) and biobanking is performed by the Biological Resource Center Lorrain BB-0033-00035. This study was supported by the Fonds IMMUNOV, for Innovation in Immunopathology and by a grant from the Agence National de la Recherche (ANR-flash Covid19 'AIROCovid' to FRL), and by the FAST Foundation (French Friends of Sheba Tel Hashomer Hospital). Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1, a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The Amsterdam UMC Covid-19 Biobank was supported by grants of the Amsterdam Corona Research Fund, Dr. C.J. Vaillant Fund, and Netherlands Organization for Health Research and Development (ZonMw, NWO-Vici-Grant [grant number 918·19·627 to DvdB]. This work was also supported by the Division of Intramural Research of the National Institute of Dental Craniofacial Research and National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by Regione Lombardia, Italy (project 'Risposta immune in pazienti con COVID-19 e comorbidita'). The opinions and assertions expressed herein are those of the author(s) and do not necessarily reflect the official policy or position of the Uniformed Services University or the Department of Defense. JH holds an Institut Imagine MD-PhD fellowship from the Fondation Bettencourt Schueller. JR is supported by the Inserm PhD program ('poste d’accueil Inserm'). PB was supported by the French Foundation for Medical Research (FRM, EA20170638020) and the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). We thank the Association 'Turner et vous' for their help and support. Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. DCV is supported by the Fonds de la recherche en santé du Québec clinician-scientist scholar program. K. Kisand was supported by the Estonian Research Council grant PUT1367. We thank the GEN-COVID Multicenter Study (https://sites.google.com/dbm.unisi.it/gen-covid). We thank the NIAID Office of Cyber Infrastructure and Computational Biology, Bioinformatics and Computational Biosciences Branch (Contract HHSN316201300006W/HHSN27200002 to MSC, Inc) and Operations Engineering Branch for developing the HGRepo system to enable streamlined access to the data and the NCI Advanced Biomedical Computational Science (ABCS) for data transformation support., The Milieu Intérieur Consortium : Laurent Abel 1, Andres Alcover 2, Hugues Aschard 2, Kalla Astrom 3, Philippe Bousso 2, Pierre Bruhns 2, Ana Cumano 2, Caroline Demangel 2, Ludovic Deriano 2, James Di Santo 2, Françoise Dromer 2, Gérard Eberl 2, Jost Enninga 2, Jacques Fellay 4, Ivo Gomperts-Boneca 2, Milena Hasan 2, Serge Hercberg 5, Olivier Lantz 6, Hugo Mouquet 2, Etienne Patin 2, Sandra Pellegrini 2, Stanislas Pol 7, Antonio Rausell 8, Lars Rogge 2, Anavaj Sakuntabhai 2, Olivier Schwartz 2, Benno Schwikowski 2, Spencer Shorte 2, Frédéric Tangy 2, Antoine Toubert 9, Mathilde Touvier 10, Marie-Noëlle Ungeheuer 2, Matthew L. Albert 11*, Darragh Duffy 2*, Lluis Quintana-Murci 2* - 1INSERM U1163, University of Paris, Imagine Institute, Paris, France. 2Pasteur Institute, Paris, France. 3Lund University, Lund, Sweden. 4EPFL, Lausanne, Switzerland. 5Université Paris 13, Paris, France. 6Curie Institute, Paris, France. 7Cochin Hospital, Paris, France. 8INSERM UMR 1163 – Institut Imagine, Paris, France. 9Hôpital Saint-Louis, Paris, France. 10Sorbonne Paris Nord University, Inserm U1153, Inrae U1125, Cnam, Nutritional Epidemiology Research Team (EREN), Bobigny, France. 11In Sitro, San Francisco, CA, USA. *Co-coordinators of The Milieu Intérieur Consortium. Additional information can be found at: www.milieuinterieur.fr/en., Amsterdam UMC Covid-19 Biobank Michiel van Agtmael1, Anna Geke Algera2, Frank van Baarle2, Diane Bax3, Martijn Beudel4, Harm Jan Bogaard5, Marije Bomers1, Lieuwe Bos2, Michela Botta2, Justin de Brabander6, Godelieve Bree6, Matthijs C. Brouwer4, Sanne de Bruin2, Marianna Bugiani7, Esther Bulle2, Osoul Chouchane1, Alex Cloherty3, Paul Elbers2, Lucas Fleuren2, Suzanne Geerlings1, Bart Geerts8, Theo Geijtenbeek9, Armand Girbes2, Bram Goorhuis1, Martin P. Grobusch1, Florianne Hafkamp9, Laura Hagens2, Jorg Hamann10, Vanessa Harris1, Robert Hemke11, Sabine M. Hermans1, Leo Heunks2, Markus W. Hollmann8, Janneke Horn2, Joppe W. Hovius1, Menno D. de Jong12, Rutger Koning4, Niels van Mourik2, Jeaninne Nellen1, Frederique Paulus2, Edgar Peters1, Tom van der Poll1, Benedikt Preckel8, Jan M. Prins1, Jorinde Raasveld2, Tom Reijnders1, Michiel Schinkel1, Marcus J. Schultz2, Alex Schuurman13, Kim Sigaloff1, Marry Smit2, Cornelis S. Stijnis1, Willemke Stilma2, Charlotte Teunissen14, Patrick Thoral2, Anissa Tsonas2, Marc van der Valk1, Denise Veelo8, Alexander P. J. Vlaar15, Heder de Vries2, Michèle van Vugt1, W. Joost Wiersinga1, Dorien Wouters16, A. H. (Koos) Zwinderman17, Diederik van de Beek18* 1Department of Infectious Diseases, Amsterdam UMC, Amsterdam, Netherlands. 2Department of Intensive Care, Amsterdam UMC, Amsterdam, Netherlands. 3Experimental Immunology, Amsterdam UMC, Amsterdam, Netherlands. 4Department of Neurology, Amsterdam UMC, Amsterdam Neuroscience, Amsterdam, Netherlands. 5Department of Pulmonology, Amsterdam UMC, Amsterdam, Netherlands. 6Department of Infectious Diseases, Amsterdam UMC, Amsterdam, Netherlands. 7Department of Pathology, Amsterdam UMC, Amsterdam, Netherlands. 8Department of Anesthesiology, Amsterdam UMC, Amsterdam, Netherlands. 9Department of Experimental Immunology, Amsterdam UMC, Amsterdam, Netherlands. 10Amsterdam UMC, Netherlands Biobank Core Facility, Amsterdam UMC, Amsterdam, Netherlands. 11Department of Radiology, Amsterdam UMC, Amsterdam, Netherlands. 12Department of Medical Microbiology, Amsterdam UMC, Amsterdam, Netherlands. 13Department of Internal Medicine, Amsterdam UMC, Amsterdam, Netherlands. 14Neurochemical Laboratory, Amsterdam UMC, Amsterdam, Netherlands. 15Deparment of Intensive Care, Amsterdam UMC, Amsterdam, Netherlands. 16Department of Clinical Chemistry, Amsterdam UMC, Amsterdam, Netherlands. 17Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, Amsterdam, Netherlands. 18Department of Neurology, Amsterdam UMC, Amsterdam, Netherlands. *Leader of the AMC consortium., COVID Human Genetic Effort Laurent Abel1, Alessandro Aiuti2, Saleh Al Muhsen3, Fahd Al-Mulla4, Mark S. Anderson5, Andrés Augusto Arias6, Hagit Baris Feldman7, Dusan Bogunovic8, Alexandre Bolze9, Anastasiia Bondarenko10, Ahmed A. Bousfiha11, Petter Brodin12, Yenan Bryceson12, Carlos D. Bustamante13, Manish Butte14, Giorgio Casari15, Samya Chakravorty16, John Christodoulou17, Elizabeth Cirulli9, Antonio Condino-Neto18, Megan A. Cooper19, Clifton L. Dalgard20, Joseph L. DeRisi21, Murkesh Desai22, Beth A. Drolet23, Sara Espinosa24, Jacques Fellay25, Carlos Flores26, Jose Luis Franco27, Peter K. Gregersen28, Filomeen Haerynck29, David Hagin30, Rabih Halwani31, Jim Heath32, Sarah E. Henrickson33, Elena Hsieh34, Kohsuke Imai35, Yuval Itan8, Timokratis Karamitros36, Kai Kisand37, Cheng-Lung Ku38, Yu-Lung Lau39, Yun Ling40, Carrie L. Lucas41, Tom Maniatis42, Davoud Mansouri43, Laszlo Marodi44, Isabelle Meyts45, Joshua D. Milner46, Kristina Mironska47, Trine Mogensen48, Tomohiro Morio49, Lisa F. P. Ng50, Luigi D. Notarangelo51, Giuseppe Novelli52, Antonio Novelli53, Cliona O'Farrelly54, Satoshi Okada55, Tayfun Ozcelik56, Rebeca Perez de Diego57, Anna M. Planas58, Carolina Prando59, Aurora Pujol60, Lluis Quintana-Murci61, Laurent Renia62, Alessandra Renieri63, Carlos Rodríguez-Gallego64, Vanessa Sancho-Shimizu65, Vijay Sankaran66, Kelly Schiabor Barrett9, Mohammed Shahrooei67, Andrew Snow68, Pere Soler-Palacín69, András N. Spaan70, Stuart Tangye71, Stuart Turvey72, Furkan Uddin73, Mohammed J. Uddin74, Diederik van de Beek75, Sara E. Vazquez76, Donald C. Vinh77, Horst von Bernuth78, Nicole Washington9, Pawel Zawadzki79, Helen C. Su51*, Jean-Laurent Casanova80* 1INSERM U1163, University of Paris, Imagine Institute, Paris, France. 2San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele, Milan, Italy. 3King Saud University, Riyadh, Saudi Arabia. 4Dasman Diabetes Institute, Department of Genetics and Bioinformatics, Dasman, Kuwait. 5University of California, San Francisco, San Francisco, CA, USA. 6Universidad de Antioquia, Group of Primary Immunodeficiencies, Antioquia, Colombia. 7The Genetics Institute, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 8Icahn School of Medicine at Mount Sinai, New York, NY, USA. 9Helix, San Mateo, CA, USA. 10Shupyk National Medical Academy for Postgraduate Education, Kiev, Ukraine. 11Clinical Immunology Unit, Pediatric Infectious Disease Department, Faculty of Medicine and Pharmacy, Averroes University Hospital, LICIA Laboratoire d'immunologie clinique, d'inflammation et d'allergie, Hassann Ii University, Casablanca, Morocco. 12Karolinska Institute, Stockholm, Sweden. 13Stanford University, Stanford, CA, USA. 14University of California, Los Angeles, CA, USA. 15Medical Genetics, IRCCS Ospedale San Raffaele, Milan, Italy. 16Department of Pediatrics and Children’s Healthcare of Atlanta, Emory University, Atlanta, GA, USA. 17Murdoch Children's Research Institute, Victoria, Australia. 18University of São Paulo, São Paulo, Brazil. 19Washington University School of Medicine, St. Louis, MO, USA. 20The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 21University of California San Francisco, Chan Zuckerberg Biohub, San Francisco, CA, USA. 22Bai Jerbai Wadia Hospital for Children, Mumbai, India. 23 School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA. 24Instituto Nacional de Pediatria (National Institute of Pediatrics), Mexico City, Mexico. 25Swiss Federal Institute of Technology Lausanne, Lausanne, Switzerland. 26Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Canarian Health System, Santa Cruz de Tenerife, Spain. 27University of Antioquia, Medellín, Colombia. 28Feinstein Institute for Medical Research, Northwell Health USA, Manhasset, NY, USA. 29Department of Paediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency Ghent (CPIG), PID Research Laboratory, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Edegem, Belgium. 30The Genetics Institute Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 31Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates. 32Institute for Systems Biology, Seattle, WA, USA. 33Children's Hospital of Philadelphia, Philadelphia, PA, USA. 34Anschutz Medical Campus, Aurora, CO, USA. 35Riken, Tokyo, Japan. 36Hellenic Pasteur Institute, Athens, Greece. 37University of Tartu, Tartu, Estonia. 38Chang Gung University, Taoyuan County, Taiwan. 39The University of Hong Kong, Hong Kong, China. 40Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 41Yale School of Medicine, New Haven, CT, USA. 42New York Genome Center, New York, NY, USA. 43Shahid Beheshti University of Medical Sciences, Tehran, Iran. 44Semmelweis University Budapest, Budapest, Hungary. 45KU Leuven, Department of Immunology, Microbiology and Transplantation, Leuven, Belgium. 46Columbia University Medical Center, New York, NY, USA. 47University Clinic for Children's Diseases, Skopje, North Macedonia. 48Aarhus University, Aarhus, Denmark. 49Tokyo Medical & Dental University Hospital, Tokyo, Japan. 50Singapore Immunology Network, Singapore. 51National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 52Department of Biomedicine and Prevention, University of Rome 'Tor Vergata,' Rome, Italy. 53Bambino Gesù Children's Hospital, Rome, Italy. 54Trinity College, Dublin, Ireland. 55Hiroshima University, Hiroshima, Japan. 56Bilkent University, Ankara, Turkey. 57Laboratory of Immunogenetics of Human Diseases, Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid, Spain. 58IIBB-CSIC, IDIBAPS, Barcelona, Spain. 59Faculdades Pequeno Príncipe e Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Brazil. 60Neurometabolic Diseases Laboratory, IDIBELL - Hospital Duran I Reynals, Catalan Institution for Research and Advanced Studies (ICREA), CIBERER U759, ISCiii Madrid Spain, Barcelona, Spain. 61Institut Pasteur (CNRS UMR2000) and Collège de France, Paris, France. 62Infectious Diseases Horizontal Technology Center and Singapore Immunology Network, Agency for Science Technology (A*STAR), Singapore. 63Medical Genetics, University of Siena, Italy, Genetica Medica, Azienda Ospedaliero-Universitaria Senese, GEN-COVID Multicenter Study, Italy. 64Hospital Universitario de Gran Canaria Dr Negrín, Canarian Health System, Canary Islands, Spain. 65Imperial College London, London, UK. 66Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. 67Saeed Pathobiology and Genetic Laboratory, Tehran, Iran. 68Uniformed Services University of the Health Sciences (USUHS), Bethesda, MD, USA. 69Hospital Universitari Vall d'Hebron, Barcelona, Spain. 70University Medical Center Utrecht, Amsterdam, Netherlands. 71Garvan Institute of Medical Research, Sydney, Australia. 72The University of British Columbia, Vancouver, Canada. 73Holy Family Red Crescent Medical College, Centre for Precision Therapeutics, NeuroGen Children's Healthcare, Genetics and Genomic Medicine Centre, NeuroGen Children's Healthcare, Dhaka, Bangladesh. 74Mohammed Bin Rashid University of Medicine and Health Sciences, College of Medicine, Dubai, United Arab Emirates, The Centre for Applied Genomics, Department of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada. 75Amsterdam UMC, University of Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam, Netherlands. 76University of California, San Francisco, San Francisco, CA, USA. 77McGill University Health Centre, Montreal, Canada. 78Charité - Berlin University Hospital Center, Berlin, Germany. 79Molecular Biophysics Division, Faculty of Physics, A. Mickiewicz University, Uniwersytetu Poznanskiego 2, Poznań, Poland. 80The Rockefeller University, Howard Hughes Medical Institute, Necker Hospital, New York, NY, USA. *Leaders of the COVID Human Genetic Effort., ANR-10-LABX-0062,IBEID,Biologie Intégrative des Maladies Infectieuses Emergentes(2011), ANR-10-LABX-0020,NUMEV,Digital and Hardware Solutions and Modeling for the Environement and Life Sciences(2010), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), Pulmonary medicine, Medical Microbiology and Infection Prevention, Internal medicine, Intensive care medicine, APH - Quality of Care, and Özçelik, Tayfun
Subjects: Male, COVID19, Immunoglobulin G, DISEASE, MESH: Antibodies, Neutralizing, 0302 clinical medicine, MESH: Interferon alpha-2, 80 and over, Medicine, Asymptomatic Infections, MESH: Immunoglobulin G, Aged, 80 and over, 0303 health sciences, MESH: Middle Aged, COVID Clinicians, MESH: Case-Control Studies, 3. Good health, Settore MED/03, 030220 oncology & carcinogenesis, MESH: Critical Illness, Interferon Type I, Science & Technology - Other Topics, Viral disease, MESH: Pandemics, [SDV.IMM] Life Sciences [q-bio]/Immunology, Critical Illness, Immunology, Pneumonia, Viral, Interferon alpha-2, HGID Lab, 03 medical and health sciences, Betacoronavirus, Genetics, Humans, MESH: SARS-CoV-2, COVID Human Genetic Effort, Aged, Autoantibodies, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, Science & Technology, CYTOKINES, MESH: Adult, Pneumonia, medicine.disease, Antibodies, Neutralizing, COVID-STORM Clinicians, MESH: Pneumonia, Viral, Case-Control Studies, NIAID-USUHS Immune Response to COVID Group, MESH: Female, MESH: Interferon Type I, MESH: Coronavirus Infections, CHRONIC MUCOCUTANEOUS CANDIDIASIS, [SDV.GEN] Life Sciences [q-bio]/Genetics, medicine.disease_cause, Autoimmunity, CoV-Contact Cohort, MESH: Aged, 80 and over, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Medicine and Health Sciences, MESH: Autoantibodies, MESH: COVID-19, Online, Viral, Chronic mucocutaneous candidiasis, Imagine COVID Group, Amsterdam UMC Covid-19 Biobank, Neutralizing, Research Articles, MESH: Aged, Multidisciplinary, biology, Middle Aged, Multidisciplinary Sciences, Milieu Intérieur Consortium, MESH: Betacoronavirus, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, medicine.symptom, Coronavirus Infections, Research Article, Sciences exactes et naturelles, Adult, INTERFERON, General Science & Technology, PROTEINS, French COVID Cohort Study Group, MESH: Asymptomatic Infections, COVID-19, Pandemics, SARS-CoV-2, Asymptomatic, Antibodies, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], 030304 developmental biology, Phenocopy, business.industry, R-Articles, Autoantibody, GAMMA, MESH: Male, 3121 General medicine, internal medicine and other clinical medicine, ANTIBODIES, biology.protein, 3111 Biomedicine, business
Abstract: HGID Lab Andrés Augusto Arias1,3, Bertrand Boisson1,2, Soraya Boucherit2, Jacinta Bustamante1,2, Marwa Chbihi2, Jie Chen1, Maya Chrabieh2, Tatiana Kochetkov1, Tom Le Voyer2, Dana Liu1, Yelena Nemirovskaya1, Masato Ogishi1, Dominick Papandrea1, Cécile Patissier2, Franck Rapaport1, Manon Roynard2, Natasha Vladikine2, Mark Woollett1, Peng Zhang1 1St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University. 2Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children. 3School of Microbiology and Group of Primary Immunodeficiencies, University of Antioquia UdeA, Medellin, Colombia., NIAID-USUHS Immune Response to COVID Group Anuj Kashyap1, Li Ding1, Marita Bosticardo1, Qinlu Wang2, Sebastian Ochoa1, Hui Liu1, Samuel D. Chauvin3, Michael Stack1, Galina Koroleva4, Neha Bansal5, Clifton L. Dalgard6,7, Andrew L. Snow8 1Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. 2Bioinformatics and Computational Biosciences Branch, NIAID Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD, USA. 3Laboratory of Immune System Biology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. 4NIH Center for Human Immunology, NIH, Bethesda, MD, USA. 5Multiscale Systems Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD, USA. 6PRIMER, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 7Department of Anatomy, Physiology & Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 8Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA., COVID Clinicians Jorge Abad1, Sergio Aguilera-Albesa2, Ozge Metin Akcan3, Ilad Alavi Darazam4, Juan C. Aldave5, Miquel Alfonso Ramos6, Seyed Alireza Nadji7, Gulsum Alkan8, Jerome Allardet-Servent9, Luis M. Allende10, Laia Alsina11, Marie-Alexandra Alyanakian12, Blanca Amador-Borrero13, Zahir Amoura14, Arnau Antolí15, Sevket Arslan16, Sophie Assant17, Terese Auguet18, Axelle Azot19, Fanny Bajolle20, Aurélie Baldolli21, Maite Ballester22, Hagit Baris Feldman23, Benoit Barrou24, Alexandra Beurton25, Agurtzane Bilbao26, Geraldine Blanchard-Rohner27, Ignacio Blanco1, Adeline Blandinières28, Daniel Blazquez-Gamero29, Marketa Bloomfield30, Mireia Bolivar-Prados31, Raphael Borie32, Ahmed A. Bousfiha33, Claire Bouvattier34, Oksana Boyarchuk35, Maria Rita P. Bueno36, Jacinta Bustamante20, Juan José Cáceres Agra37, Semra Camli38, Ruggero Capra39, Maria Carrabba40, Carlos Casasnovas41, Marion Caseris42, Martin Castelle43, Francesco Castelli44, Martín Castillo de Vera45, Mateus V. Castro36, Emilie Catherinot46, Martin Chalumeau47, Bruno Charbit48, Matthew P. Cheng49, Père Clavé31, Bonaventura Clotet50, Anna Codina51, Fatih Colkesen52, Fatma Colkesen53, Roger Colobran 54, Cloé Comarmond55, Angelo G. Corsico56, David Dalmau57, David Ross Darley58, Nicolas Dauby59, Stéphane Dauger60, Loic de Pontual61, Amin Dehban62, Geoffroy Delplancq63, Alexandre Demoule64, Antonio Di Sabatino65, Jean-Luc Diehl66, Stephanie Dobbelaere67, Sophie Durand68, Waleed Eldars69, Mohamed Elgamal70, Marwa H. Elnagdy71, Melike Emiroglu72, Emine Hafize Erdeniz73, Selma Erol Aytekin74, Romain Euvrard75, Recep Evcen76, Giovanna Fabio40, Laurence Faivre77, Antonin Falck42, Muriel Fartoukh78, Morgane Faure79, Miguel Fernandez Arquero80, Carlos Flores81, Bruno Francois82, Victoria Fumadó83, Francesca Fusco84, Blanca Garcia Solis85, Pascale Gaussem86, Juana Gil-Herrera87, Laurent Gilardin88, Monica Girona Alarcon89, Mónica Girona-Alarcón89, Jean-Christophe Goffard90, Funda Gok91, Rafaela González-Montelongo92, Antoine Guerder93, Yahya Gul94, Sukru Nail Guner94, Marta Gut95, Jérôme Hadjadj96, Filomeen Haerynck97, Rabih Halwani98, Lennart Hammarström99, Nevin Hatipoglu100, Elisa Hernandez-Brito101, María Soledad Holanda-Peña102, Juan Pablo Horcajada103, Sami Hraiech104, Linda Humbert105, Alejandro D. Iglesias106, Antonio Íñigo-Campos92, Matthieu Jamme107, María Jesús Arranz108, Iolanda Jordan109, Fikret Kanat110, Hasan Kapakli111, Iskender Kara112, Adem Karbuz113, Kadriye Kart Yasar114, Sevgi Keles115, Yasemin Kendir Demirkol116, Adam Klocperk117, Zbigniew J. Król118, Paul Kuentz119, Yat Wah M. Kwan120, Jean-Christophe Lagier121, Yu-Lung Lau122, Fleur Le Bourgeois60, Yee-Sin Leo123, Rafael Leon Lopez124, Daniel Leung122, Michael Levin125, Michael Levy60, Romain Lévy20, Zhi Li48, Agnes Linglart126, José M. Lorenzo-Salazar92, Céline Louapre127, Catherine Lubetzki127, Charles-Edouard Luyt128, David C. Lye129, Davood Mansouri130, Majid Marjani131, Jesus Marquez Pereira132, Andrea Martin133, David Martínez Pueyo134, Javier Martinez-Picado135, Iciar Marzana136, Alexis Mathian14, Larissa R. B. Matos36, Gail V. Matthews137, Julien Mayaux138, Jean-Louis Mège139, Isabelle Melki140, Jean-François Meritet141, Ozge Metin142, Isabelle Meyts143, Mehdi Mezidi144, Isabelle Migeotte145, Maude Millereux146, Tristan Mirault147, Clotilde Mircher68, Mehdi Mirsaeidi148, Abián Montesdeoca Melián149, Antonio Morales Martinez150, Pierre Morange151, Demence Mordacq105, Guillaume Morelle152, Stéphane Mouly13, Adrián Muñoz-Barrera92, Cyril Nafati153, João Farela Neves154, Lisa F. P. Ng155, Yeray Novoa Medina156, Esmeralda Nuñez Cuadros157, J. Gonzalo Ocejo-Vinyals158, Zerrin Orbak159, Mehdi Oualha20, Tayfun Özçelik160, Qiang Pan Hammarström161, Christophe Parizot138, Tiffany Pascreau162, Estela Paz-Artal163, Sandra Pellegrini48, Rebeca Pérez de Diego85, Aurélien Philippe164, Quentin Philippot78, Laura Planas-Serra165, Dominique Ploin166, Julien Poissy167, Géraldine Poncelet42, Marie Pouletty168, Paul Quentric138, Didier Raoult139, Anne-Sophie Rebillat68, Ismail Reisli169, Pilar Ricart170, Jean-Christophe Richard171, Nadia Rivet28, Jacques G. Rivière172, Gemma Rocamora Blanch15, Carlos Rodrigo1, Carlos Rodriguez-Gallego173, Agustí Rodríguez-Palmero174, Carolina Soledad Romero175, Anya Rothenbuhler176, Flore Rozenberg177, Maria Yolanda Ruiz del Prado178, Joan Sabater Riera15, Oliver Sanchez179, Silvia Sánchez-Ramón180, Agatha Schluter165, Matthieu Schmidt181, Cyril E. Schweitzer182, Francesco Scolari183, Anna Sediva184, Luis M. Seijo185, Damien Sene13, Sevtap Senoglu114, Mikko Seppänen186, Alex Serra Ilovich187, Mohammad Shahrooei62, David Smadja188, Ali Sobh189, Xavier Solanich Moreno15, Jordi Solé-Violán190, Catherine Soler191, Pere Soler-Palacín133, Yuri Stepanovskiy192, Annabelle Stoclin193, Fabio Taccone145, Yacine Tandjaoui-Lambiotte194, Jean-Luc Taupin195, Simon J. Tavernier196, Benjamin Terrier197, Caroline Thumerelle105, Gabriele Tomasoni198, Julie Toubiana47, Josep Trenado Alvarez199, Sophie Trouillet-Assant200, Jesús Troya201, Alessandra Tucci202, Matilde Valeria Ursini‬84, Yurdagul Uzunhan203, Pierre Vabres204, Juan Valencia-Ramos205, Ana Maria Van Den Rym85, Isabelle Vandernoot206, Hulya Vatansev207, Valentina Vélez-Santamaria41, Sébastien Viel166, Cédric Vilain208, Marie E. Vilaire68, Audrey Vincent34, Guillaume Voiriot209, Fanny Vuotto105, Alper Yosunkaya91, Barnaby E. Young123, Fatih Yucel210, Faiez Zannad211, Mayana Zatz36, Alexandre Belot212* 1University Hospital and Research Institute “Germans Trias i Pujol”, Badalona, Spain. 2Navarra Health Service Hospital, Pamplona, Spain. 3Division of Pediatric Infectious Diseases, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 4Department of Infectious Diseases, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 5Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru. 6Parc Sanitari Sant Joan de Déu, Sant Boi de Llobregat Spain. 7Virology Research Center, National institutes of Tuberculosis and Lung diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 8Division of Pediatric Infectious Diseases, Faculty of Medicine, Selcuk University, Konya, Turkey. 9Intensive care unit, Hôpital Européen, Marseille, France. 10Immunology Department, University Hospital 12 de Octubre. Research Institute imas12. Complutense University, Madrid, Spain. 11Hospital Sant Joan de Déu, Barcelona, Spain. 12Department of Biological Immunology, Necker Hospital for Sick Children, APHP and INEM, Paris, France. 13Internal medicine department, Hôpital Lariboisière, APHP; Université de Paris, Paris, France. 14Internal medicine department, Pitié-Salpétrière Hospital, Paris, France. 15Hospital Universitari de Bellvitge, Barcelona, Spain. 16Division of Clinical Immunology and Allergy, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 17Joint Research Unit, Hospices Civils de Lyon-bio Mérieux, Hospices Civils de Lyon, Lyon Sud Hospital, Lyon, France. 18Hospital U. de Tarragona Joan XXIII. Universitat Rovira i Virgili (URV). IISPV, Tarragona, Spain. 19Private practice, Paris, France. 20Necker Hospital for Sick Children, AP-HP, Paris, France. 21Department of Infectious Diseases, CHU de Caen, Caen, France. 22Consorcio Hospital General Universitario, Valencia, Spain. 23The Genetics Institute, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 24Dept Urology, Nephrology, Transplantation, APHP-SU, Sorbonne Université, INSERM U 1082, Paris, France. 25Service de Médecine Intensive–Réanimation et Pneumologie, APHP Hôpital Pitié–Salpêtrière, Paris, France. 26Cruces University Hospital, Bizkaia, Spain. 27Paediatric Immunology and Vaccinology Unit, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland. 28Hematology, Georges Pompidou Hospital, APHP, Paris, France. 29Pediatric Infectious Diseases Unit. Instituto de Investigación 12 de Octubre (imas12). Hospital Universitario 12 de Octubre, Madrid, Spain. 30Department of Immunology, Motol University Hospital, 2nd Faculty of Medicine, Charles University, Department of Pediatrics, Thomayer’s Hospital, 1st Faculty of Medicine, Charles University, Prague, Czech Republic. 31Centro de Investigación Biomédica en Red de Enfermedades Hepàticas y Digestivas (Ciberehd). Hospital de Mataró, Consorci Sanitari del Maresme, Mataró, Spain. 32Service de Pneumologie, Hopital Bichat, APHP, Paris, France. 33Clinical immunology unit, pediatric infectious disease departement, Faculty of Medicine and Pharmacy, Averroes University Hospital. LICIA Laboratoire d'immunologie clinique, d'inflammation et d'allergie, Hassann Ii University, Casablanca, Morocco. 34Endocrinology unit, APHP Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, France. 35Department of Children's Diseases and Pediatric Surgery, I.Horbachevsky Ternopil National Medical University, Ternopil, Ukraine. 36Human Genome and stem-cell research center- University of São Paulo, São Paulo, Brazil. 37Hospital Insular, Las Palmas de Gran Canaria, Spain. 38Division of Critical Care Medicine, Department of Anesthesiology and Reanimation, Konya State Hospital, Konya, Turkey. 39MS Center, Spedali Civili, Brescia, Italy. 40Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 41Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain. 42Hopital Robert Debré, Paris, France. 43Pediatric Immuno-hematology Unit, Necker Enfants Malades Hospital, AP-HP, Paris, France. 44Department of Infectious and Tropical Diseases, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy. 45Doctoral Health Care Center, Canarian Health System, Las Palmas de Gran Canaria, Spain. 46Hôpital Foch, Suresnes, France. 47Necker Hospital for Sick Children, Paris University, AP-HP, Paris, France. 48Pasteur Institute, Paris, France. 49McGill University Health Centre, Montreal, Canada. 50University Hospital and Research Institute “Germans Trias i Pujol”, IrsiCaixa AIDS Research Institute, UVic-UCC, Badalona, Spain. 51Clinical Biochemistry, Pathology, Paediatric Neurology and Molecular Medicine Departments and Biobank, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, Esplugues, Spain. 52Division of Clinical Immunology and Allergy, Department of Internal Medicine, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 53Department of Infectious Diseases and Clinical Microbiology, Konya Training and Research Hospital, Konya, Turkey. 54Hospital Universitari Vall d’Hebron, Barcelona, Spain. 55Pitié-Salpêtrière Hospital, Paris, France. 56Respiratory Diseases Division, IRCCS Policlinico San Matteo Foundation and University of Pavia, Pavia, Italy. 57Fundació Docència i Recerca Mútua Terrassa, Barcelona, Spain. 58UNSW Medicine, St Vincent's Clinical School; Department of Thoracic Medicine, St Vincent's Hospital Darlinghurst, Sidney, Australia. 59CHU Saint-Pierre, Université Libre de Bruxelles (ULB), Brussels, Belgium. 60Pediatric Intensive Care Unit, Robert-Debré University Hospital, APHP, Paris, France. 61Sorbonne Paris Nord, Hôpital Jean Verdier, APHP, Bondy, France. 62Specialized Immunology Laboratory of Dr. Shahrooei, Sina Medical Complex, Ahvaz, Iran. 63Centre de génétique humaine, CHU Besançon, Besançon, France. 64Sorbonne Université médecine and APHP Sorbonne université site Pitié-Salpêtrière, Paris, France. 65Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy. 66Intensive Care unit, Georges Pompidou Hospital, APHP, Paris, France. 67Department of Pneumology, AZ Delta, Roeselare, Belgium. 68Institut Jérôme Lejeune, Paris, France. 69Department of Microbiology and Immunology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 70Department of Chest, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 71Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 72Faculty of Medicine, Division of Pediatric Infectious Diseases, Selcuk University, Konya, Turkey. 73Division of Pediatric Infectious Diseases, Ondokuz Mayıs University, Samsun, Turkey. 74Necmettin Erbakan University, Meram Medical Faculty, Division of Pediatric Allergy and Immunology, Konya, Turkey. 75Centre Hospitalier Fleyriat, Bourg-en-Bresse, France. 76Division of Clinical Immunology and Allergy, Department of Internal Medicine, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 77Centre de Génétique, CHU Dijon, Dijon, France. 78APHP Tenon Hospital, Paris, France. 79Sorbonne Universités, UPMC University of Paris, Paris, France. 80Department of Clinical Immunology, Hospital Clínico San Carlos, Madrid, Spain. 81Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Santa Cruz de Tenerife, Spain; CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain; Research Unit, Hospital Universitario N.S. de Candelaria, Santa Cruz de Tenerife, Spain; Instituto de Tecnologías Biomédicas (ITB), Universidad de La Laguna, San Cristóbal de La Laguna, Spain. 82CHU Limoges and Inserm CIC 1435 & UMR 1092, Limoges, France. 83Infectious Diseases Unit, Department of Pediatrics, Hospital Sant Joan de Déu, Barcelona, Spain; Institut de Recerca Sant Joan de Déu, Spain; Universitat de Barcelona (UB), Barcelona, Spain. 84Institute of Genetics and Biophysics ‘Adriano Buzzati-Traverso’, IGB-CNR, Naples, Italy. 85Laboratory of Immunogenetics of Human Diseases, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid, Spain. 86Hematology, APHP, Hopital Européen Georges Pompidou and Inserm UMR-S1140, Paris, France. 87Hospital General Universitario and Instituto de Investigación Sanitaria "Gregorio Marañón", Madrid, Spain. 88Bégin military Hospital, Bégin, France. 89Pediatric Intensive Care Unit, Hospital Sant Joan de Déu, Barcelona, Spain. 90Department of Internal Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. 91Division of Critical Care Medicine, Department of Anesthesiology and Reanimation, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 92Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Santa Cruz de Tenerife, Spain. 93Assistance Publique Hôpitaux de Paris, Paris, France. 94Division of Allergy and Immunology, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 95CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST); Universitat Pompeu Fabra (UPF), Barcelona, Spain. 96Department of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, APHP-CUP, Hôpital Cochin, Paris, France. 97Ghent University Hospital, Ghent, Belgium. 98Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, UAE. 99Department of Biosciences and Nutrition, SE14183, Huddinge, Karolinska Institutet, Stockholm, Sweden. 100Pediatric Infectious Diseases Unit, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, University of Health Sciences, Istanbul, Turkey. 101Department of Immunology, Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Spain. 102IntensivenCare Unit. Marqués de Valdecilla Hospital, Santander, Spain. 103Hospital del Mar, Parc de Salut Mar, Barcelona, Spain. 104Intensive care unit, APHM, Marseille, France. 105CHU Lille, Lille, France. 106Department of Pediatrics, Columbia University, New York, NY, USA. 107Centre hospitalier intercommunal Poissy Saint Germain en Laye, Poissy, France. 108Division of Respiratory Diseases, Fundació Docència i Recerca Mútua Terrassa, Barcelona, Spain. 109Hospital Sant Joan de Déu, Kids Corona Platfform, Barcelona, Spain. 110Selcuk University, Faculty of Medicine, Chest Diseases Department, Konya, Turkey. 111Division of Allergy and Immunology, Balikesir Ataturk City Hospital, Balikesir, Turkey. 112Division of Critical Care Medicine, Selcuk University, Faculty of Medicine, Konya, Turkey. 113Division of Pediatric Infectious Diseases, Prof. Dr. Cemil Tascıoglu City Hospital, Istanbul, Turkey. 114Departments of Infectious Diseases and Clinical Microbiology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, University of Health Sciences, Istanbul, Turkey. 115Meram Medical Faculty, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 116Health Sciences University, Umraniye Education and Research Hospital, Istanbul, Turkey. 117Department of Immunology, 2nd Faculty of Medicine, Charles University and University Hospital in Motol, Prague, Czech Republic. 118Central Clinical Hospital of Ministry of the Interior and Administration in Warsaw, Warsaw, Poland. 119Oncobiologie Génétique Bioinformatique, PC Bio, CHU Besançon, Besançon, France. 120Paediatric Infectious Disease Unit, Hospital Authority Infectious Disease Center, Princess Margaret Hospital, Hong Kong (Special Administrative Region), China. 121Aix Marseille Univ, IRD, MEPHI, IHU Méditerranée Infection, Marseille, France. 122Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, China. 123National Centre for Infectious Diseases, Singapore. 124Hospital Universitario Reina Sofía, Cordoba, Spain. 125Imperial College, London, England. 126Endocrinology and diabetes for children, AP-HP, Bicêtre Paris-Saclay hospital, Le Kremlin-Bicêtre, France. 127Neurology unit, APHP Pitié-Salpêtrière Hospital, Paris University, Paris, France. 128Intensive care unit, APHP Pitié-Salpêtrière Hospital, Paris University, Paris, France. 129National Centre for Infectious Diseases; Tan Tock Seng Hospital; Yong Loo Lin School of Medicine; Lee Kong Chian School of Medicine, Singapore. 130Department of Clinical Immunology and Infectious Diseases, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 131Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. 132Hospital Sant Joan de Déu and University of Barcelona, Barcelona, Spain. 133Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron, Vall d'Hebron Research Institute, Vall d’Hebron Barcelona Hospital Campus. Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. 134Hospital Universitari Mutua de Terrassa, Universitat de Barcelona, Barcelona, Spain. 135IrsiCaixa AIDS Research Institute, ICREA, UVic-UCC, Research Institute “Germans Trias i Pujol”, Badalona, Spain. 136Department of Laboratory, Cruces University Hospital, Barakaldo, Bizkaia, Spain. 137University of New South Wales, Australia. 138APHP Pitié-Salpêtrière Hospital, Paris, France. 139Aix-Marseille University, APHM, Marseille, France. 140Robert Debré Hospital, Paris, France. 141APHP Cohin Hospital, Paris, France. 142Necmettin Erbakan University Meram Faculty of Medicine Department of Pediatric Infectious Diseases, Konya, Turkey. 143University Hospitals Leuven, Leuven, Belgium. 144Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Lyon, France. 145Hôpital Erasme, Brussels, Belgium. 146CH Gonesse, Gonesse, France. 147Vascular Medicine, Georges Pompidou Hospital, APHP, Paris, France. 148Division of Pulmonary and Critical Care, University of Miami, Miami, USA. 149Guanarteme Health Care Center, Canarian Health System, Las Palmas de Gran Canaria, Spain. 150Regional University Hospital of Malaga, Malaga, Spain. 151Aix-Marseille Université, Marseille, France. 152Department of General Paediatrics, Hôpital Bicêtre, AP-HP, University of Paris Saclay, Le Kremlin-Bicêtre, France. 153CHU de La Timone, Marseille, France. 154Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal. 155Infectious Diseases Horizontal Technlogy Centre, A*STAR; Singapore Immunology Network, A*STAR, Singapore. 156Department of Pediatrics, Complejo Hospitalario Universitario Insular-Materno Infantil, Canarian Health System, Las Palmas de Gran Canaria, Spain. 157Regional Universitary Hospital of Malaga, Málaga, Spain. 158Hospital Universitario Marqués de Valdecilla, Santander, Spain. 159Ataturk University Medical Faculty, Erzurum, Turkey. 160Bilkent University, Department of Molecular Biology and Genetics, Ankara, Turkey. 161Department of Laboratory Medicine, Karolinska Institutet, SE14186, Stockholm, Sweden. 162L'Hôpital Foch, Suresnes, France. 163Department of Immunology, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain. 164APHP Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, France. 165Neurometabolic Diseases Laboratory, IDIBELL-Hospital Duran i Reynals, Barcelona; CIBERER U759, ISCiii Madrid, Spain. 166Hospices Civils de Lyon, Lyon, France. 167Université de Lille, Inserm U1285, CHU Lille, Paris, France. 168Departement of General Pediatrics, University Hospital Robert Debré, APHP, Paris, France. 169Necmettin Erbakan University, Konya, Turkey. 170Germans Trias i Pujol Hospital, Badalona, Spain. 171Medical intensive care unit. Hopital de la Croix-Rousse. Hospices Civils de Lyon, Lyon, France. 172Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron, Vall d'Hebron Research Institute, Vall d’Hebron Barcelona Hospital Campus., Barcelona, Spain. 173Department of Immunology, Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Spain, EU. University Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain. 174Neurometabolic Diseases Laboratory, IDIBELL-Hospital Duran i Reynals, Barcelona, Spain. 175Consorcio Hospital General Universitario, Valencia, Spain. 176APHP Hôpitaux Universitaires Paris-Sud, Paris, France. 177Virology unit, Université de Paris, Cohin Hospital, APHP, Paris, France. 178Hospital San Pedro, Logroño, Spain. 179Respiratory medicine, Georges Pompidou Hospital, APHP, Paris, France. 180Dept. Immunology, Hospital Clínico San Carlos, Madrid, Spain. 181Service de Médecine Intensive Réanimation, Institut de Cardiologie, Hopital Pitié-Salpêtrière, Paris, France. 182CHRU de Nancy, Hôpital d'Enfants, Vandoeuvre, France. 183Chair of Nephrology, University of Brescia, Brescia, Italy. 184Department of Immunology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic. 185Clínica Universidad de Navarra, Madrid, Spain. 186HUS Helsinki University Hospital, Children and Adolescents, Rare Disease Center, and Inflammation Center, Adult Immunodeficiency Unit, Majakka, Helsinki, Finland. 187Fundació Docència i Recerca Mútua Terrassa, Terrassa, Spain. 188Hopital Européen Georges Pompidou, Paris, France. 189Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 190Critical Care Unit, Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Spain. 191CHU de Saint Etienne, Saint-Priest-en-Jarez, France. 192Shupyk National Medical Academy for Postgraduate Education, Kiev, Ukraine. 193Gustave Roussy Cancer Campus, Villejuif, France. 194Intensive Care Unit, Avicenne Hospital, APHP, Bobigny, France. 195Laboratory of Immunology and Histocompatibility, Saint-Louis Hospital, Paris University, Paris, France. 196Department of Internal Diseases and Pediatrics, Primary Immune Deficiency Research Lab, Centre for Primary Immunodeficiency Ghent, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Ghent, Belgium. 197Department of Internal Medicine, Université de Paris, INSERM, U970, PARCC, F-75015, Paris, France. 198First Division of Anesthesiology and Critical Care Medicine, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy. 199Intensive Care Department, Hospital Universitari MutuaTerrassa, Universitat Barcelona, Terrassa, Spain. 200Hospices Civils de Lyon, Lyon Sud Hospital, Lyon, France. 201Infanta Leonor University Hospital, Madrid, Spain. 202Hematology Department, ASST Spedali Civili di Brescia, Brescia, Italy. 203Pneumologie, Hôpital Avicenne, APHP, INSERM U1272, Université Sorbonne Paris Nord, Bobigny, France. 204Dermatology unit, Laboratoire GAD, INSERM UMR1231 LNC, université de Bourgogne, Dijon, France. 205University Hospital of Burgos, Burgos, Spain. 206Center of Human Genetics, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. 207Department of Chest Diseases, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 208CHU de Caen, Caen, France. 209Sorbonne Université, Service de Médecine Intensive Réanimation, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France. 210General Intensive Care Unit, Konya Training and Research Hospital, Konya, Turkey. 211CHU de Nancy, Nancy, France. 212University of Lyon, CIRI, INSERM U1111, National referee centre RAISE, Pediatric Rheumatology, HFME, Hospices Civils de Lyon, Lyon, France. *Leader of the COVID-clinicians group., COVID-STORM Clinicians Giuseppe Foti1, Giacomo Bellani1, Giuseppe Citerio1, Ernesto Contro1, Alberto Pesci2, Maria Grazia Valsecchi3, Marina Cazzaniga4 1Department of Emergency, Anesthesia and Intensive Care, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT. 2Department of Pneumology, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT. 3Center of Bioinformatics and Biostatistics, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT. 4Phase I Research Center, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT., Imagine COVID Group Christine Bole-Feysot1, Stanislas Lyonnet1*, Cécile Masson1, Patrick Nitschke1, Aurore Pouliet1, Yoann Schmitt1, Frederic Tores1, Mohammed Zarhrate1 1Imagine Institute, Université de Paris, INSERM UMR 1163, Paris, France. *Leader of the Imagine COVID group., French COVID Cohort Study Group Laurent Abel1, Claire Andrejak2, François Angoulvant3, Delphine Bachelet4, Romain Basmaci5, Sylvie Behillil6, Marine Beluze7, Dehbia Benkerrou8, Krishna Bhavsar4, François Bompart9, Lila Bouadma4, Maude Bouscambert10, Mireille Caralp11, Minerva Cervantes-Gonzalez12, Anissa Chair4, Alexandra Coelho13, Camille Couffignal4, Sandrine Couffin-Cardiergues14, Eric D’ortenzio12, Charlene Da Silveira4, Marie-Pierre Debray4, Dominique Deplanque15, Diane Descamps16, Mathilde Desvallées17, Alpha Diallo18, Alphonsine Diouf13, Céline Dorival8, François Dubos19, Xavier Duval4, Philippine Eloy4, Vincent V. E. Enouf20, Hélène Esperou21, Marina Esposito-Farese4, Manuel Etienne22, Nadia Ettalhaoui4, Nathalie Gault4, Alexandre Gaymard10, Jade Ghosn4, Tristan Gigante23, Isabelle Gorenne4, Jérémie Guedj24, Alexandre Hoctin13, Isabelle Hoffmann4, Salma Jaafoura21, Ouifiya Kafif4, Florentia Kaguelidou25, Sabina Kali4, Antoine Khalil4, Coralie Khan17, Cédric Laouénan4, Samira Laribi4, Minh Le4, Quentin Le Hingrat4, Soizic Le Mestre18, Hervé Le Nagard24, François-Xavier Lescure4, Yves Lévy26, Claire Levy-Marchal27, Bruno Lina10, Guillaume Lingas24, Jean Christophe Lucet4, Denis Malvy28, Marina Mambert13, France Mentré4, Noémie Mercier18, Amina Meziane8, Hugo Mouquet20, Jimmy Mullaert4, Nadège Neant24, Marion Noret29, Justine Pages30, Aurélie Papadopoulos21, Christelle Paul18, Nathan Peiffer-Smadja4, Ventzislava Petrov-Sanchez18, Gilles Peytavin4, Olivier Picone31, Oriane Puéchal12, Manuel Rosa-Calatrava10, Bénédicte Rossignol23, Patrick Rossignol32, Carine Roy4, Marion Schneider4, Caroline Semaille12, Nassima Si Mohammed4, Lysa Tagherset4, Coralie Tardivon4, Marie-Capucine Tellier4, François Téoulé8, Olivier Terrier10, Jean-François Timsit4, Théo Treoux4, Christelle Tual33, Sarah Tubiana4, Sylvie van der Werf34, Noémie Vanel35, Aurélie Veislinger33, Benoit Visseaux16, Aurélie Wiedemann26, Yazdan Yazdanpanah36 1Inserm UMR 1163, Paris, France. 2CHU Amiens, France. 3Hôpital Necker, Paris, France. 4Hôpital Bichat, Paris, France. 5Hôpital Louis Mourrier, Colombes, France. 6Institut Pasteur, Paris, France. 7F-CRIN Partners Platform, AP-HP, Université de Paris, Paris, France. 8Inserm UMR 1136, Paris, France. 9Drugs for Neglected Diseases initiative, Geneva, Switzerland. 10Inserm UMR 1111, Lyon, France. 11Inserm Transfert, Paris, France. 12REACTing, Paris, France. 13Inserm UMR 1018, Paris, France. 14Inserm, Pôle Recherche Clinique, France. 15CIC 1403 Inserm-CHU Lille, Paris, France. 16Université de Paris, IAME, INSERM UMR 1137, AP-HP, University hospital Bichat Claude Bernard, Virology, F-75018 Paris, France. 17Inserm UMR 1219, Bordeaux, France. 18ANRS, Paris, France. 19CHU Lille, France. 20Pasteur Institute, Paris, France. 21Inserm sponsor, Paris, France. 22Rouen - SMIT, France. 23FCRIN INI-CRCT, Nancy, France. 24Inserm UMR 1137, Paris, France. 25Centre d'Investigation Clinique, Inserm CIC1426, Hôpital Robert Debré, Paris, France. 26Inserm UMR 955, Créteil, France; Vaccine Research Instiute (VRI), Paris, France. 27F-CRIN INI-CRCT, Paris, France. 28Bordeaux - SMIT, France. 29RENARCI, Annecy, France. 30Hôpital Robert Debré, Paris, France. 31Colombes - Louis Mourier - Gynécologie, France. 32University of Lorraine, Plurithematic Clinical Investigation Centre Inserm CIC-P; 1433, Inserm U1116, CHRU Nancy Hopitaux de Brabois, F-CRIN INI-CRCT; (Cardiovascular and Renal Clinical Trialists), Nancy, France. 33Inserm CIC-1414, Rennes, France. 34Institut Pasteur, UMR 3569 CNRS, Université de Paris, Paris, France. 35hôpital la timone, Marseille, France. 36Paris - Bichat - SMIT, France., The Milieu Intérieur Consortium Laurent Abel1, Andres Alcover2, Hugues Aschard2, Kalla Astrom3, Philippe Bousso2, Pierre Bruhns2, Ana Cumano2, Caroline Demangel2, Ludovic Deriano2, James Di Santo2, Françoise Dromer2, Gérard Eberl2, Jost Enninga2, Jacques Fellay4, Ivo Gomperts-Boneca2, Milena Hasan2, Serge Hercberg5, Olivier Lantz6, Hugo Mouquet2, Etienne Patin2, Sandra Pellegrini2, Stanislas Pol7, Antonio Rausell8, Lars Rogge2, Anavaj Sakuntabhai2, Olivier Schwartz2, Benno Schwikowski2, Spencer Shorte2, Frédéric Tangy2, Antoine Toubert9, Mathilde Touvier10, Marie-Noëlle Ungeheuer2, Matthew L. Albert11*, Darragh Duffy2*, Lluis Quintana-Murci2* 1INSERM U1163, University of Paris, Imagine Institute, Paris, France. 2Pasteur Institute, Paris, France. 3Lund University, Lund, Sweden. 4EPFL, Lausanne, Switzerland. 5Université Paris 13, Paris, France. 6Curie Institute, Paris, France. 7Cochin Hospital, Paris, France. 8INSERM UMR 1163 – Institut Imagine. 9Hôpital Saint-Louis, Paris, France. 10Université Paris 13, Paris, France. 11In Sitro. *Co-coordinators of the Milieu Intérieur Consortium. Additional information can be found at: https://www.pasteur.fr/labex/milieu-interieur., CoV-Contact Cohort Loubna Alavoine1, Karine K. A. Amat2, Sylvie Behillil3, Julia Bielicki4, Patricia Bruijning5, Charles Burdet6, Eric Caumes7, Charlotte Charpentier8, Bruno Coignard9, Yolande Costa1, Sandrine Couffin-Cardièrgues10, Florence Damond8, Aline Dechanet11, Christelle Delmas10, Diane Descamps8, Xavier Duval1, Jean-Luc Ecobichon1, Vincent Enouf3, Hélène Espérou10, Wahiba Frezouls1, Nadhira Houhou11, Emila Ilic-Habensus1, Ouifiya Kafif11, John Kikoine11, Quentin Le Hingrat8, David Lebeaux12, Anne Leclercq1, Jonathan Lehacaut1, Sophie Letrou1, Bruno Lina13, Jean-Christophe Lucet14, Denis Malvy15, Pauline Manchon11, Milica Mandic1, Mohamed Meghadecha16, Justina Motiejunaite17, Mariama Nouroudine1, Valentine Piquard11, Andreea Postolache11, Caroline Quintin1, Jade Rexach1, Layidé Roufai10, Zaven Terzian11, Michael Thy18, Sarah Tubiana1, Sylvie van der Werf3, Valérie Vignali1, Benoit Visseaux8, Yazdan Yazdanpanah14 1Centre d'Investigation Clinique, Inserm CIC 1425, Hôpital Bichat Claude Bernard, APHP, Paris, France. 2IMEA Fondation Léon M'Ba, Paris, France. 3Institut Pasteur, UMR 3569 CNRS, Université de Paris, Paris, France. 4University of Basel Children’s Hospital. 5Julius Center for Health Sciences and Primary Care, Utrecht. 6Université de Paris, IAME, Inserm UMR 1137, F-75018, Paris, France, Hôpital Bichat Claude Bernard, APHP, Paris, France. 7Hôpital Pitiè Salpétriere, APHP, Paris. 8Université de Paris, IAME, INSERM UMR 1137, AP-HP, University hospital Bichat Claude Bernard, Virology, F-75018 Paris, France. 9Santé Publique France, Saint Maurice, France. 10Pole Recherche Clinique, Inserm, Paris France. 11Hôpital Bichat Claude Bernard, APHP, Paris, France. 12APHP, Paris, France. 13Virpath Laboratory, International Center of Research in Infectiology, Lyon University, INSERM U1111, CNRS UMR 5308, ENS, UCBL, Lyon, France . 14IAME Inserm UMR 1138, Hôpital Bichat Claude Bernard, APHP, Paris, France. 15Service des Maladies Infectieuses et Tropicales; Groupe Pellegrin-Place Amélie-Raba-Léon, BORDEAUX. 16Hôpital Hotel Dieu, APHP, Paris, France. 17ervice des explorations fonctionnelles, Hôpital Bichat- Claude Bernard, APHP, Paris, France. 18Center for Clinical Investigation, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital., Amsterdam UMC Covid-19 Biobank Michiel van Agtmael1, Anne Geke Algera2, Frank van Baarle2, Diane Bax3, Martijn Beudel4, Harm Jan Bogaard5, Marije Bomers1, Lieuwe Bos2, Michela Botta2, Justin de Brabander6, Godelieve Bree6, Matthijs C. Brouwer4, Sanne de Bruin2, Marianna Bugiani7, Esther Bulle2, O. Chouchane1, Alex Cloherty3, Paul Elbers2, Lucas Fleuren2, Suzanne Geerlings1, Bart Geerts8, Theo Geijtenbeek9, Armand Girbes2, Bram Goorhuis1, Martin P. Grobusch1, Florianne Hafkamp9, Laura Hagens2, Jorg Hamann10, Vanessa Harris1, Robert Hemke11, Sabine M. Hermans1, Leo Heunks2, Markus Hollmann8, Janneke Horn2, Joppe W. Hovius1, Menno de Jong12, Rutger Koning4, Mourik van Mourik2, Jeaninne Nellen1, Frederique Paulus2, Edgar Peters1, Tom van der Poll1, Bennedikt Preckel8, Jan M. Prins1, Jorinde Raasveld2, Tom Reijnders1, Michiel Schinkel1, Marcus Schultz2, Alex Schuurman13, Kim Sigaloff1, Marry Smit2, Cornelis S. Stijnis1, Willemke Stilma2, Charlotte Teunissen14, Patrick Thoral2, Anissa Tsonas2, Marc van der Valk1, Denise Veelo8, Alexander P. J. Vlaar15, Heder de Vries2, Michèle van Vugt1, W. Joost Wiersinga1, Dorien Wouters16, A. H. (Koos) Zwinderman17, Diederik van de Beek18* 1Department of Infectious Diseases, Amsterdam UMC, Netherlands. 2Department of Intensive Care, Amsterdam UMC, Netherlands. 3Experimental Immunology, Amsterdam UMC, Netherlands. 4Department of Neurology, Amsterdam UMC, Netherlands. 5Department of Pulmonology, Amsterdam UMC, Netherlands. 6Department of Infectious Diseases, Amsterdam UMC, Netherlands. 7Department of Pathology, Amsterdam UMC, Netherlands. 8Department of Anesthesiology, Amsterdam UMC, Netherlands. 9Department of Experimental Immunology, Amsterdam UMC, Netherlands. 10Amsterdam UMC, THE NETHERLANDS Biobank Core Facility, Amsterdam UMC, Netherlands. 11Department of Radiology, Amsterdam UMC, Netherlands. 12Department of Medical Microbiology, Amsterdam UMC, Netherlands. 13Department of Internal Medicine, Amsterdam UMC, Netherlands. 14Neurochemical Laboratory, Amsterdam UMC, Netherlands. 15Deparment of Intensive Care, Amsterdam UMC, Netherlands. 16Department of Clinical Chemistry, Amsterdam UMC, Netherlands. 17Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, Netherlands. 18Department of Neurology, Amsterdam UMC, Netherlands. *Leader of the AMC consortium., COVID Human Genetic Effort Laurent Abel1, Alessandro Aiuti2, Saleh Al Muhsen3, Fahd Al-Mulla4, Mark S. Anderson5, Andrés Augusto Arias6, Hagit Baris Feldman7, Dusan Bogunovic8, Alexandre Bolze9, Anastasiia Bondarenko10, Ahmed A. Bousfiha11, Petter Brodin12, Yenan Bryceson12, Carlos D. Bustamante13, Manish Butte14, Giorgio Casari15, Samya Chakravorty16, John Christodoulou17, Elizabeth Cirulli9, Antonio Condino Neto18, Megan A. Cooper19, Clifton L. Dalgard20, Joseph L. DeRisi21, Murkesh Desai22, Beth A. Drolet23, Sara Espinosa24, Jacques Fellay25, Carlos Flores26, Jose Luis Franco27, Peter K. Gregersen28, Filomeen Haerynck29, David Hagin30, Rabih Halwani31, Jim Heath32, Sarah E. Henrickson33, Elena Hsieh34, Kohsuke Imai35, Yuval Itan8, Timokratis Karamitros36, Kai Kisand37, Cheng-Lung Ku38, Yu-Lung Lau39, Yun Ling40, Carrie L. Lucas41, Tom Maniatis42, Davoud Mansouri43, Laszlo Marodi44, Isabelle Meyts45, Joshua Milner46, Kristina Mironska47, Trine Mogensen48, Tomohiro Morio49, Lisa P. Ng50, Luigi D. Notarangelo51, Giuseppe Novelli52, Antonio Novelli53, Cliona O'Farrelly54, Satoshi Okada55, Tayfun Ozcelik56, Rebeca Perez de Diego57, Anna M. Planas58, Carolina Prando59, Aurora Pujol60, Lluis Quintana-Murci61, Laurent Renia62, Alessandra Renieri63, Carlos Rodríguez-Gallego64, Vanessa Sancho-Shimizu65, Vijay Sankaran66, Kelly Schiabor Barrett9, Mohammed Shahrooei67, Andrew Snow68, Pere Soler-Palacín69, András N. Spaan70, Stuart Tangye71, Stuart Turvey72, Furkan Uddin73, Mohammed J. Uddin74, Diederik van de Beek75, Sara E. Vazquez76, Donald C. Vinh77, Horst von Bernuth78, Nicole Washington9, Pawel Zawadzki79, Helen C. Su51*, Jean-Laurent Casanova80* 1INSERM U1163, University of Paris, Imagine Institute, Paris, France. 2San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele, Milan, Italy. 3King Saud University, Riyadh, Saudi Arabia. 4Kuwait University, Kuwait City, Kuwait. 5University of California, San Francisco, San Francisco, CA, USA. 6Universidad de Antioquia, Group of Primary Immunodeficiencies, Antioquia, Colombia. 7The Genetics Institute, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 8Icahn School of Medicine at Mount Sinai, New York, NY, USA. 9Helix, San Mateo, CA, USA. 10Shupyk National Medical Academy for Postgraduate Education, Kiev, Ukraine. 11Clinical immunology unit, pediatric infectious disease departement, Faculty of Medicine and Pharmacy, Averroes University Hospital. LICIA Laboratoire d'immunologie clinique, d'inflammation et d'allergie, Hassann Ii University., Casablanca, Morocco. 12Karolinska Institute, Stockholm, Sweden. 13Stanford University, Stanford, CA, USA. 14University of California, Los Angeles, CA, USA. 15Medical Genetics, IRCCS Ospedale San Raffaele, Milan, Italy. 16Emory, Atlanta, GA, USA. 17Murdoch Children's Research Institute, Victoria, Australia. 18University of São Paulo, São Paulo, Brazil. 19Washington University School of Medicine, St. Louis, MO, USA. 20The American Genome Center; Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 21University of California San Francisco; Chan Zuckerberg Biohub, San Francisco, CA, United States. 22Bai Jerbai Wadia Hospital for Children, Mumbai, India. 23 School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA. 24Instituto Nacional de Pediatria (National Institute of Pediatrics), Mexico City, Mexico. 25Swiss Federal Institute of Technology Lausanne, Lausanne, Switzerland. 26Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Canarian Health System, Santa Cruz de Tenerife, Spain. 27University of Antioquia, Medellín, Colombia. 28Feinstein Institute for Medical Research, Northwell Health USA, Manhasset, NY, USA. 29Department of Paediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency Ghent (CPIG), PID research lab, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Edegem, Belgium. 30The Genetics Institute Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 31Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, UAE. 32Institute for Systems Biology, Seattle, WA, USA. 33Children's Hospital of Philadelphia, Philadelphia, PA, USA. 34Anschutz Medical Campus, Aurora, CO, USA. 35Riken, Tokyo, Japan. 36Hellenic Pasteur Institute, Athens, Greece. 37University of Tartu, Tartu, Estonia. 38Chang Gung University, Taoyuan County, Taiwan. 39The University of Hong Kong, Hong Kong, China. 40Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 41Yale School of Medicine, New Haven, CT, USA. 42New York Genome Center, New York, NY, USA. 43Shahid Beheshti University of Medical Sciences, Tehran, Iran. 44Semmelweis University Budapest, Budapest, Hungary. 45KU Leuven, Department of Immunology, Microbiology and Transplantation, Leuven, Belgium. 46Columbia University Medical Center, New York, NY, USA. 47University Clinic for Children's Diseases, Skopje, North Macedonia. 48Aarhus University, Aarhus, Denmark. 49Tokyo Medical & Dental University Hospital, Tokyo, Japan. 50Singapore Immunology Network, Singapore. 51National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 52Bambino Gesù Children's Hospital, Rome, Italy; Dept. Biomedicine and Prevention, University of Rome “Tor Vergata”, Rome, Italy. 53Bambino Gesù Children's Hospital, Rome, Italy, Rome, Italy, Italy. 54Trinity College, Dublin, Ireland. 55Hiroshima University, Hiroshima, Japan. 56Bilkent University, Ankara, Turkey. 57Laboratory of Immunogenetics of Human Diseases, Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid 28046, Spain, EU, Madrid, Spain, Spain. 58IIBB-CSIC, IDIBAPS, Barcelona, Spain. 59Faculdades Pequeno Príncipe e Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Brazil. 60Neurometabolic Diseases Laboratory, IDIBELL- Hospital Duran I Reynals; Catalan Institution for Research and Advanced Studies (ICREA); CIBERER U759, ISCiii Madrid Spain, Barcelona, Spain. 61Institut Pasteur (CNRS UMR2000) and Collège de France, Paris, France. 62Infectious Diseases Horizontal Technology Center and Singapore Immunology Network, Agency for Science Technology (A*STAR), Singapore. 63University of Siena, Siena, Italy. 64Hospital Universitario de Gran Canaria Dr Negrín, Canarian Health System, Canary Islands, Spain. 65Imperial College London, London, UK. 66Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. 67Saeed Pathobiology and Genetic Lab, Tehran, Iran. 68Uniformed Services University of the Health Sciences (USUHS), Bethesda, MD, USA. 69Hospital Universitari Vall d'Hebron, Barcelona, Spain. 70University Medical Center Utrecht, Amsterdam, Netherlands. 71Garvan Institute of Medical Research, Sydney, Australia. 72The University of British Columbia, Vancouver, Canada. 73Holy Family Red Crescent Medical College; Centre for Precision Therapeutics, NeuroGen Children's Healthcare; Genetics and Genomic Medicine Centre, NeuroGen Children's Healthcare, Dhaka, Bangladesh. 74Mohammed Bin Rashid University of Medicine and Health Sciences, College of Medicine, Dubai, UAE; The Centre for Applied Genomics, Department of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada, Dhaka, Bangladesh. 75Amsterdam UMC, Amsterdam, Netherlands. 76University of California, San Francisco, San Francisco, CA, United States. 77McGill University Health Centre, Montreal, Canada. 78Charité - Berlin University Hospital Center, Berlin, Germany. 79Molecular Biophysics Division, Faculty of Physics, A. Mickiewicz University, Uniwersytetu Poznanskiego 2, Poznań, Poland. 80Rockefeller University, Howard Hughes Medical Institute, Necker Hospital, New York, NY, USA. *Leaders of the COVID Human Genetic Effort., Interindividual clinical variability in the course of SARS-CoV-2 infection is immense. We report that at least 101 of 987 patients with life-threatening COVID-19 pneumonia had neutralizing IgG auto-Abs against IFN-ω (13 patients), the 13 types of IFN-α (36), or both (52), at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1,227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 were men. A B cell auto-immune phenocopy of inborn errors of type I IFN immunity underlies life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men., The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62- IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project, ANRS-COV05, the Square Foundation, Grandir - Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, Institut Institut National de la Santé et de la Recherche Médicale (INSERM) and the University of Paris. Samples from San Raffaele Hospital were obtained within the Covid-BioB project and healthcare personnel of San Raffaele Hospital, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) clinical lab and clinical research Unit; funded by the Program Project COVID-19 OSR-UniSR and Fondazione Telethon. The French COVID Cohort study group was sponsored by Inserm and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). The “Milieu Intérieur” cohort was supported by was supported by the French Government’s Investissement d’Avenir Program, Laboratoire d’Excellence “Milieu Intérieur” Grant (ANR-10-LABX-69-01) (PI: L QuintanaMurci & D Duffy). The Simoa experiment was supported by the PHRC-20-0375 COVID-19 grant “DIGITAL COVID” (PI: G Gorochov). SGT is supported by a Leadership 3 Investigator Grant awarded by the National Health and Medical Research Council of Australia, and a COVID19 Rapid Response Grant awarded by UNSW Sydney. CRG and colleagues were supported by Instituto de Salud Carlos III (COV20_01333 and COV20_01334, Spanish Ministry of Science and Innovation -RTC-2017-6471-1; AEI/FEDER, UE), and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). SA and AB were supported by ANR-20-COVI-0064 (PI: A Belot). This work is supported by the French Ministry of Health “Programme Hospitalier de Recherche Clinique Inter regional 2013”, by the Contrat de Plan Etat-Lorraine and FEDER Lorraine, and a public grant overseen by the French National Research Agency (ANR) as part of the second “Investissements d’Avenir” program FIGHT-HF (reference: ANR-15-RHU-0004) and by the French PIA project “Lorraine Université d’Excellence”, reference ANR15-IDEX-04-LUE (45) and biobanking is performed by the Biological Resource Center Lorrain BB-0033-00035. This study was supported by the Fonds IMMUNOV, for Innovation in Immunopathology and by a grant from the Agence National de la Recherche (ANR-flash Covid19 “AIROCovid” to FRL), and by the FAST Foundation (French Friends of Sheba Tel Hashomer Hospital). Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1, a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The Amsterdam UMC Covid-19 Biobank was supported by grants of the Amsterdam Corona Research Fund, Dr. C.J. Vaillant Fund, and Netherlands Organization for Health Research and Development (ZonMw; NWO-Vici-Grant [grant number 918·19·627 to DvdB]. This work was also supported by the Division of Intramural Research of the National Institute of Dental Craniofacial Research and National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by Regione Lombardia, Italy (project “Risposta immune in pazienti con COVID-19 e comorbidita”). The opinions and assertions expressed herein are those of the author(s) and do not necessarily reflect the official policy or position of the Uniformed Services University or the Department of Defense. JH holds an Institut Imagine MD-PhD fellowship from the Fondation Bettencourt Schueller. JR is supported by the Inserm PhD program (“poste d’accueil Inserm”). PB was supported by the French Foundation for Medical Research (FRM, EA20170638020) and the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). We thank the Association “Turner et vous” for their help and support. Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. DCV is supported by the Fonds de la recherche en santé du Québec clinician-scientist scholar program. K. Kisand was supported by the Estonian Research Council grant PUT1367. We thank the GEN-COVID Multicenter Study (https://sites.google.com/dbm.unisi.it/gen-covid). We thank the NIAID Office of Cyber Infrastructure and Computational Biology, Bioinformatics and Computational Biosciences Branch (Contract HHSN316201300006W/HHSN27200002 to MSC, Inc) and Operations Engineering Branch for developing the HGRepo system to enable streamlined access to the data and the NCI Advanced Biomedical Computational Science (ABCS) for data transformation support.
Published: 2020

7. X-linked recessive TLR7 deficiency in similar to 1% of men under 60 years old with life-threatening COVID-19

Author: Asano T, Boisson B, Onodi F, Matuozzo D, Moncada-Velez M, Renkilaraj M, Zhang P, Meertens L, Bolze A, Materna M, Korniotis S, Gervais A, Talouarn E, Bigio B, Seeleuthner Y, Bilguvar K, Zhang Y, Neehus A, Ogishi M, Pelham S, Le Voyer T, Rosain J, Philippot Q, Soler-Palacin P, Colobran R, Martin-Nalda A, Riviere J, Tandjaoui-Lambiotte Y, Chaibi K, Shahrooei M, Darazam I, Olyaei N, Mansouri D, Palabiyik F, Ozcelik T, Novelli G, Novelli A, Casari G, Aiuti A, Carrera P, Bondesan S, Barzaghi F, Rovere-Querini P, Tresoldi C, Franco J, Rojas J, Reyes L, Bustos I, Arias A, Morelle G, Kyheng C, Troya J, Planas-Serra L, Schluter A, Gut M, Pujol A, Allende L, Rodriguez-Gallego C, Flores C, Cabrera-Marante O, Pleguezuelo D, de Diego R, Keles S, Aytekin G, Akcan O, Bryceson Y, Bergman P, Brodin P, Smole D, Smith C, Norlin A, Campbell T, Covill L, Hammarstrom L, Pan-Hammarstrom Q, Abolhassani H, Mane S, Marr N, Ata M, Al Ali F, Khan T, Spaan A, Dalgard C, Bonfanti P, Biondi A, Tubiana S, Burdet C, Nussbaum R, Kahn-Kirby A, Snow A, Bustamante J, Puel A, Boisson-Dupuis S, Zhang S, Beziat V, Lifton R, Bastard P, Notarangelo L, Abel L, Su H, Jouanguy E, Amara A, Soumelis V, Cobat A, Zhang Q, Casanova J, COVID Human Genetic Efft, COVID-STORM Cliniciano, COVID Clinicians, Imagine COVID Grp, French COVID Cohort Study Grp, Cov-Contact Cohort, Amsterdam UMC Covid-19 Biobank, and NIAID-USUHS Covid Study Grp
Subjects: virus diseases
Abstract: Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean, 36.7 years) from a cohort of 1202 male patients aged 0.5 to 99 years (mean, 52.9 years) with unexplained critical COVID-19 pneumonia. None of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean, 38.7 years) tested carry such TLR7 variants (P = 3.5 x 10(-5)). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (n = 2) or moderate (n = 1), severe (n = 1), or critical (n = 1) pneumonia. Two patients from a cohort of 262 male patients with severe COVID-19 pneumonia (mean, 51.0 years) are hemizygous for a deleterious TLR7 variant. The cumulative allele frequency for deleterious TLR7 variants in the male general population is
Published: 2021

8. 064 Genome analysis reveals UV signature mutations in sun-exposed skin tumors in tuberous sclerosis complex

Author: Zhang, X., primary, Wang, J., additional, Roy, J., additional, Cartron, A., additional, Wu, H., additional, Jones, A., additional, Julien-Williams, P., additional, Wilkerson, M., additional, Dalgard, C., additional, Moss, J., additional, and Darling, T., additional
Published: 2021
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9. Correction to: Large‑scale pathway specific polygenic risk and transcriptomic community network analysis identifies novel functional pathways in Parkinson disease

Author: Bandres-Ciga, S., Saez-Atienzar, S., Kim, J. J., Makarious, M. B., Faghri, F., Diez-Fairen, M., Iwaki, H., Leonard, H., Botia, J., Ryten, M., Hernandez, D., Gibbs, J. R., Ding, J., Gan-Or, Z., Noyce, A., Pihlstrom, L., Torkamani, A., Soltis, A. R., Dalgard, C. L., Scholz, S. W., Traynor, B. J., Ehrlich, D., Scherzer, C. R., Bookman, M., Cookson, M., Blauwendraat, C., Nalls, M. A., and Singleton, A. B.
Subjects: Multifactorial Inheritance, Cellular and Molecular Neuroscience, Dopaminergic Neurons, Gene Expression Profiling, Correction, Humans, Genetic Predisposition to Disease, Parkinson Disease, Neurology (clinical), Lysosomes, Community Networks, Mitochondria, Pathology and Forensic Medicine
Abstract: Polygenic inheritance plays a central role in Parkinson disease (PD). A priority in elucidating PD etiology lies in defining the biological basis of genetic risk. Unraveling how risk leads to disruption will yield disease-modifying therapeutic targets that may be effective. Here, we utilized a high-throughput and hypothesis-free approach to determine biological processes underlying PD using the largest currently available cohorts of genetic and gene expression data from International Parkinson's Disease Genetics Consortium (IPDGC) and the Accelerating Medicines Partnership-Parkinson's disease initiative (AMP-PD), among other sources. We applied large-scale gene-set specific polygenic risk score (PRS) analyses to assess the role of common variation on PD risk focusing on publicly annotated gene sets representative of curated pathways. We nominated specific molecular sub-processes underlying protein misfolding and aggregation, post-translational protein modification, immune response, membrane and intracellular trafficking, lipid and vitamin metabolism, synaptic transmission, endosomal-lysosomal dysfunction, chromatin remodeling and apoptosis mediated by caspases among the main contributors to PD etiology. We assessed the impact of rare variation on PD risk in an independent cohort of whole-genome sequencing data and found evidence for a burden of rare damaging alleles in a range of processes, including neuronal transmission-related pathways and immune response. We explored enrichment linked to expression cell specificity patterns using single-cell gene expression data and demonstrated a significant risk pattern for dopaminergic neurons, serotonergic neurons, hypothalamic GABAergic neurons, and neural progenitors. Subsequently, we created a novel way of building de novo pathways by constructing a network expression community map using transcriptomic data derived from the blood of PD patients, which revealed functional enrichment in inflammatory signaling pathways, cell death machinery related processes, and dysregulation of mitochondrial homeostasis. Our analyses highlight several specific promising pathways and genes for functional prioritization and provide a cellular context in which such work should be done.
Published: 2021

10. ELEVATED MIR-155 PROMOTES INFLAMMATION IN CYSTIC FIBROSIS BY DRIVING HYPER-EXPRESSION OF INTERLEUKIN-8: 242

Author: Biswas, R., Bhattacharyya, S., Balakathiresan, N., Dalgard, C. L., Jozwik, C., Srivastava, M., and Pollard, H. B.
Published: 2011

11. ABERRANT TRANSCRIPTION AND SPLICING OF IL8 CONTRIBUTE TO INTRINSIC HYPERACTIVATION OF PROINFLAMMATORY IL8 IN CYSTIC FIBROSIS BRONCHIAL EPITHELIUM: 142

Author: Torosyan, Y., Dalgard, C. L., Dobi, A., Mueller, G. P., Srivastava, M., and Pollard, H. B.
Published: 2011

12. 258 Mosaicism in tuberous sclerosis complex detected by genome analysis

Author: Cartron, A.M., primary, Zhang, X., additional, Treichel, A., additional, Pithadia, D., additional, Steagall, W., additional, Jones, A., additional, Julien-Williams, P., additional, Wilkerson, M., additional, Dalgard, C., additional, Moss, J., additional, and Darling, T., additional
Published: 2020
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13. Large-scale pathway specific polygenic risk and transcriptomic community network analysis identifies novel functional pathways in Parkinson disease.

Author: Bandres-Ciga, S., Saez-Atienzar, S., Kim, J. J., Makarious, M. B., Faghri, F., Diez-Fairen, M., Iwaki, H., Leonard, H., Botia, J., Ryten, M., Hernandez, D., Gibbs, J. R., Ding, J., Gan-Or, Z., Noyce, A., Pihlstrom, L., Torkamani, A., Soltis, A. R., Dalgard, C. L., and Scholz, S. W.
Subjects: PARKINSON'S disease, POST-translational modification, GENE expression, LIPID metabolism, DOPAMINERGIC neurons, MONOGENIC & polygenic inheritance (Genetics), LYSOSOMES
Abstract: Polygenic inheritance plays a central role in Parkinson disease (PD). A priority in elucidating PD etiology lies in defining the biological basis of genetic risk. Unraveling how risk leads to disruption will yield disease-modifying therapeutic targets that may be effective. Here, we utilized a high-throughput and hypothesis-free approach to determine biological processes underlying PD using the largest currently available cohorts of genetic and gene expression data from International Parkinson's Disease Genetics Consortium (IPDGC) and the Accelerating Medicines Partnership-Parkinson's disease initiative (AMP-PD), among other sources. We applied large-scale gene-set specific polygenic risk score (PRS) analyses to assess the role of common variation on PD risk focusing on publicly annotated gene sets representative of curated pathways. We nominated specific molecular sub-processes underlying protein misfolding and aggregation, post-translational protein modification, immune response, membrane and intracellular trafficking, lipid and vitamin metabolism, synaptic transmission, endosomal–lysosomal dysfunction, chromatin remodeling and apoptosis mediated by caspases among the main contributors to PD etiology. We assessed the impact of rare variation on PD risk in an independent cohort of whole-genome sequencing data and found evidence for a burden of rare damaging alleles in a range of processes, including neuronal transmission-related pathways and immune response. We explored enrichment linked to expression cell specificity patterns using single-cell gene expression data and demonstrated a significant risk pattern for dopaminergic neurons, serotonergic neurons, hypothalamic GABAergic neurons, and neural progenitors. Subsequently, we created a novel way of building de novo pathways by constructing a network expression community map using transcriptomic data derived from the blood of PD patients, which revealed functional enrichment in inflammatory signaling pathways, cell death machinery related processes, and dysregulation of mitochondrial homeostasis. Our analyses highlight several specific promising pathways and genes for functional prioritization and provide a cellular context in which such work should be done. [ABSTRACT FROM AUTHOR]
Published: 2020
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14. 162 CXCL12 is a potential paracrine factor in tuberous sclerosis tumorigenesis

Author: Li, S., primary, Klover, P., additional, Dalgard, C., additional, Wang, J., additional, Moss, J., additional, and Darling, T., additional
Published: 2018
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15. The MCP-4/MCP-1 ratio in plasma is a candidate circadian biomarker for chronic post-traumatic stress disorder

Author: Dalgard, C, primary, Eidelman, O, additional, Jozwik, C, additional, Olsen, C H, additional, Srivastava, M, additional, Biswas, R, additional, Eudy, Y, additional, Rothwell, S W, additional, Mueller, G P, additional, Yuan, P, additional, Drevets, W C, additional, Manji, H K, additional, Vythlingam, M, additional, Charney, D S, additional, Neumeister, A, additional, Ursano, R J, additional, Jacobowitz, D M, additional, Pollard, H B, additional, and Bonne, O, additional
Published: 2017
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16. Heavier smoking may lead to a relative increase in waist circumference: Evidence for a causal relationship from a Mendelian randomisation meta-analysis. The CARTA consortium

Author: Morris, R.W., Taylor, A.E., Fluharty, M.E., Bjorngaard, J.H., Asvold, B.O., Elvestad Gabrielsen, M., Campbell, A., Marioni, R., Kumari, M., Korhonen, T., Männistö, S., Marques-Vidal, P., Kaakinen, M., Cavadino, A., Postmus, I., Husemoen, L.L.N., Skaaby, T., Ahluwalia, T.S., Treur, J.L., Willemsen, G., Dale, C., Wannamethee, S.G., Lahti, J., Palotie, A., Räikkönen, K., McConnachie, A., Padmanabhan, S., Wong, A., Dalgard, C., Paternoster, L., Ben-Shlomo, Y., Tyrrell, J., Horwood, J., Fergusson, D.M., Kennedy, M.A., Nohr, E.A., Christiansen, L., Kyvik, K.O., Kuh, D, Watt, G., Eriksson, J.G., Whincup, P.H., Vink, J.M., Boomsma, D.I., Davey Smith, G., Lawlor, D., Linneberg, A., Ford, I., Jukema, J.W., Power, C., Hyppönen, E., Jarvelin, M.R., Preisig, M., Borodulin, K., Kaprio, J., Kivimaki, M., Smith, B.H., Hayward, C., Romundstad, P.R., Sørensen, T.I.A., Munafò, M., Sattar, N., Medical Research Council (MRC), Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, and EMGO+ - Lifestyle, Overweight and Diabetes
Subjects: Adult, Male, Netherlands Twin Register (NTR), Adolescent, GENETICS, Aged, Body Mass Index, Female, Humans, Mendelian Randomization Analysis, Middle Aged, Obesity, Abdominal/complications, Sex Factors, Smoking/adverse effects, Smoking/genetics, Waist Circumference, Waist-Hip Ratio, Young Adult, Brain and Behaviour, Medicine, General & Internal, SDG 3 - Good Health and Well-being, General & Internal Medicine, EPIDEMIOLOGY, CORONARY-HEART-DISEASE, WEIGHT CONCERNS, Smoking and Tobacco, Science & Technology, MORTALITY, Research, Tobacco and Alcohol, Smoking, WOMEN, MEN, ASSOCIATION, BODY-MASS INDEX, Obesity, Abdominal, RISK-FACTORS, ADIPOSITY, CIGARETTE-SMOKING, Life Sciences & Biomedicine, Developmental Psychopathology
Abstract: OBJECTIVES: To investigate, using a Mendelian randomisation approach, whether heavier smoking is associated with a range of regional adiposity phenotypes, in particular those related to abdominal adiposity.DESIGN: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730 in the CHRNA5-CHRNA3-CHRNB4 gene region) as a proxy for smoking heaviness, of the associations of smoking heaviness with a range of adiposity phenotypes.PARTICIPANTS: 148 731 current, former and never-smokers of European ancestry aged ≥16 years from 29 studies in the consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA).PRIMARY OUTCOME MEASURES: Waist and hip circumferences, and waist-hip ratio.RESULTS: The data included up to 66 809 never-smokers, 43 009 former smokers and 38 913 current daily cigarette smokers. Among current smokers, for each extra minor allele, the geometric mean was lower for waist circumference by -0.40% (95% CI -0.57% to -0.22%), with effects on hip circumference, waist-hip ratio and body mass index (BMI) being -0.31% (95% CI -0.42% to -0.19), -0.08% (-0.19% to 0.03%) and -0.74% (-0.96% to -0.51%), respectively. In contrast, among never-smokers, these effects were higher by 0.23% (0.09% to 0.36%), 0.17% (0.08% to 0.26%), 0.07% (-0.01% to 0.15%) and 0.35% (0.18% to 0.52%), respectively. When adjusting the three central adiposity measures for BMI, the effects among current smokers changed direction and were higher by 0.14% (0.05% to 0.22%) for waist circumference, 0.02% (-0.05% to 0.08%) for hip circumference and 0.10% (0.02% to 0.19%) for waist-hip ratio, for each extra minor allele.CONCLUSIONS: For a given BMI, a gene variant associated with increased cigarette consumption was associated with increased waist circumference. Smoking in an effort to control weight may lead to accumulation of central adiposity. OBJECTIVES: To investigate, using a Mendelian randomisation approach, whether heavier smoking is associated with a range of regional adiposity phenotypes, in particular those related to abdominal adiposity.DESIGN: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730 in the CHRNA5-CHRNA3-CHRNB4 gene region) as a proxy for smoking heaviness, of the associations of smoking heaviness with a range of adiposity phenotypes.PARTICIPANTS: 148 731 current, former and never-smokers of European ancestry aged ≥16 years from 29 studies in the consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA).PRIMARY OUTCOME MEASURES: Waist and hip circumferences, and waist-hip ratio.RESULTS: The data included up to 66 809 never-smokers, 43 009 former smokers and 38 913 current daily cigarette smokers. Among current smokers, for each extra minor allele, the geometric mean was lower for waist circumference by -0.40% (95% CI -0.57% to -0.22%), with effects on hip circumference, waist-hip ratio and body mass index (BMI) being -0.31% (95% CI -0.42% to -0.19), -0.08% (-0.19% to 0.03%) and -0.74% (-0.96% to -0.51%), respectively. In contrast, among never-smokers, these effects were higher by 0.23% (0.09% to 0.36%), 0.17% (0.08% to 0.26%), 0.07% (-0.01% to 0.15%) and 0.35% (0.18% to 0.52%), respectively. When adjusting the three central adiposity measures for BMI, the effects among current smokers changed direction and were higher by 0.14% (0.05% to 0.22%) for waist circumference, 0.02% (-0.05% to 0.08%) for hip circumference and 0.10% (0.02% to 0.19%) for waist-hip ratio, for each extra minor allele.CONCLUSIONS: For a given BMI, a gene variant associated with increased cigarette consumption was associated with increased waist circumference. Smoking in an effort to control weight may lead to accumulation of central adiposity.
Published: 2015

17. 401 Dermal fibroblasts with loss of TSC2 express increased galectin-3, a potential biomarker for tuberous sclerosis complex

Author: Klover, P., primary, Thangapazham, R., additional, Kato, J., additional, Wang, J., additional, Li, S., additional, Dalgard, C., additional, Wilkerson, M., additional, Mccart, E., additional, Moss, J., additional, and Darling, T., additional
Published: 2016
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18. 742 Augmentation of HGF signaling: Potential for enhancing hair follicle neogenesis and development in bioengineered skin

Author: Thangapazham, R., primary, Mungunsukh, O., additional, Sukumar, G., additional, Dalgard, C., additional, Wilkerson, M., additional, Day, R., additional, and Darling, T., additional
Published: 2016
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19. Pregnancy and cord vitamin D status and symptoms of autism spectrum disorders in toddlers: An Odense child cohort study

Author: Clausen, S.S.B., Christesen, H.T., Dalgård, C., Lykkedegn, S., Munk-Jørgensen, P., and Bilenberg, N.
Published: 2017
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20. P-049: A short leukocyte telomere length predicts insulin resistance

Author: Verhulst, S., Dalgård, C., Labat, C., Kark, J.D., Kimura, M., Christensen, K., Toupance, S., Aviv, A., Kyvik, K.O., and Benetos, A.
Published: 2015
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21. Mammalian Expression Cloning of Nucleic Acid Binding Proteins by Agarose Thin-Layer Gelshift Clone Selection

Author: Dobi, A., primary, Debnam, W., additional, Dalgard, C., additional, Owusu, A., additional, and Agoston, D.v., additional
Published: 2002
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22. Mercury in the Umbilical Cord: Implications for Risk Assessment for Minamata Disease.

Author: Dalgard, C, primary, Grandjean, P, additional, Jorgensen, PJ, additional, and Weihe, P, additional
Published: 1994
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23. Functional partitioning of beta1 integrins revealed by activating and inhibitory mAbs.

Author: Cruz, M T, Dalgard, C L, and Ignatius, M J
Abstract: Integrins exist in different activation states on the surfaces of cells. Addition of the proper signal, ligand, or antibody can alter the activation state of these molecules. We report here the identification of two immunocytochemically distinct populations of beta1 integrins on fixed embryonic chick dermal fibroblasts. One population, recognized by the integrin activating mAb TASC, localizes to discrete regions of the cell, most likely focal contacts. These integrins co-localize with other proteins, such as vinculin and F-actin, and their retention at these sites is dependent on the actin cytoskeleton. The other population, identified with the inhibitory mAb W1B10, is more evenly distributed throughout the cell surface, and its pattern remains unchanged after disruption of the actin cytoskeleton. Double labeling experiments using Fab fragments of TASC alongside whole W1B10 IgG revealed non-overlapping staining patterns. These results show that it is possible to visualize and study discrete populations of integrins on cell surfaces using two different antibodies. We hypothesize that these antibodies report differences in the distribution of receptors in two different states. A model is proposed describing the ligand independent recruitment of integrins based on these findings and results from other labs.
Published: 1997

24. Histone deacetylase inhibitors SAHA and sodium butyrate block G1-to-S cell cycle progression in neurosphere formation by adult subventricular cells

Author: Doughty Martin L, Wynder Christopher, Dalgard Clifton L, and Zhou Qiong
Subjects: suberoylanilide hydroxamic acid, vorinostat, sodium butyrate, cyclin-dependant kinase inhibitor, p21 (Cip1/Waf1/Cdkn1a), p27 (Kip1/Cdkn1b), cell cycle, chromatin immunoprecipitation, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurophysiology and neuropsychology, QP351-495
Abstract: Abstract Background Histone deacetylases (HDACs) are enzymes that modulate gene expression and cellular processes by deacetylating histones and non-histone proteins. While small molecule inhibitors of HDAC activity (HDACi) are used clinically in the treatment of cancer, pre-clinical treatment models suggest they also exert neuroprotective effects and stimulate neurogenesis in neuropathological conditions. However, the direct effects of HDACi on cell cycle progression and proliferation, two properties required for continued neurogenesis, have not been fully characterized in adult neural stem cells (NSCs). In this study, we examined the effects of two broad class I and class II HDACi on adult mouse NSCs, the hydroxamate-based HDACi suberoylanilide hydroxamic acid (vorinostat, SAHA) and the short chain fatty acid HDACi sodium butyrate. Results We show that both HDACi suppress the formation of neurospheres by adult mouse NSCs grown in proliferation culture conditions in vitro. DNA synthesis is significantly inhibited in adult mouse NSCs exposed to either SAHA or sodium butyrate and inhibition is associated with an arrest in the G1 phase of the cell cycle. HDACi exposure also resulted in transcriptional changes in adult mouse NSCs. Cdk inhibitor genes p21 and p27 transcript levels are increased and associated with elevated H3K9 acetylation levels at proximal promoter regions of p21 and p27. mRNA levels for notch effector Hes genes and Spry-box stem cell transcription factors are downregulated, whereas pro-neural transcription factors Neurog1 and Neurod1 are upregulated. Lastly, we show HDAC inhibition under proliferation culture conditions leads to long-term changes in cell fate in adult mouse NSCs induced to differentiate in vitro. Conclusion SAHA and sodium butyrate directly regulate cdk inhibitor transcription to control cell cycle progression in adult mouse NSCs. HDAC inhibition results in G1 arrest in adult mouse NSCs and transcriptional changes associated with activation of neuronal lineage commitment programs and a reduction of stem/progenitor state. Changes in differentiated cell state in adult mouse NSCs treated with HDACi under proliferation culture conditions suggests an intrinsic relationship between multipotency, cell cycle progression and HDAC activity in these cells.
Published: 2011
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25. X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19

Author: Asano, Takaki, Boisson, Bertrand, Onodi, Fanny, Matuozzo, Daniela, Moncada-Velez, Marcela, Maglorius Renkilaraj, Majistor Raj Luxman, Zhang, Peng, Meertens, Laurent, Bolze, Alexandre, Materna, Marie, Korniotis, Sarantis, Gervais, Adrian, Talouarn, Estelle, Bigio, Benedetta, Seeleuthner, Yoann, Bilguvar, Kaya, Zhang, Yu, Neehus, Anna-Lena, Ogishi, Masato, Pelham, Simon J., Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Soler-Palacín, Pere, Colobran, Roger, Martin-Nalda, Andrea, Rivière, Jacques G., Tandjaoui-Lambiotte, Yacine, Chaïbi, Khalil, Shahrooei, Mohammad, Darazam, Ilad Alavi, Olyaei, Nasrin Alipour, Mansouri, Davood, Hatipoğlu, Nevin, Palabiyik, Figen, Ozcelik, Tayfun, Novelli, Giuseppe, Novelli, Antonio, Casari, Giorgio, Aiuti, Alessandro, Carrera, Paola, Bondesan, Simone, Barzaghi, Federica, Rovere-Querini, Patrizia, Tresoldi, Cristina, Franco, Jose Luis, Rojas, Julian, Reyes, Luis Felipe, Bustos, Ingrid G., Arias, Andres Augusto, Morelle, Guillaume, Kyheng, Christèle, Troya, Jesús, Planas-Serra, Laura, Schlüter, Agatha, Gut, Marta, Pujol, Aurora, Allende, Luis M., Rodriguez-Gallego, Carlos, Flores, Carlos, Cabrera-Marante, Oscar, Pleguezuelo, Daniel E., Pérez de Diego, Rebeca, Keles, Sevgi, Aytekin, Gokhan, Metin Akcan, Ozge, Bryceson, Yenan T., Bergman, Peter, Brodin, Petter, Smole, Daniel, Smith, C. I. Edvard, Norlin, Anna-Carin, Campbell, Tessa M., Covill, Laura E., Hammarström, Lennart, Pan-Hammarström, Qiang, Abolhassani, Hassan, Mane, Shrikant, Marr, Nico, Ata, Manar, Al Ali, Fatima, Khan, Taushif, Spaan, András N., Dalgard, Clifton L., Bonfanti, Paolo, Biondi, Andrea, Tubiana, Sarah, Burdet, Charles, Nussbaum, Robert, Kahn-Kirby, Amanda, Snow, Andrew L., Bustamante, Jacinta, Puel, Anne, Boisson-Dupuis, Stéphanie, Zhang, Shen-Ying, Béziat, Vivien, Lifton, Richard P., Bastard, Paul, Notarangelo, Luigi D., Abel, Laurent, Su, Helen C., Jouanguy, Emmanuelle, Amara, Ali, Soumelis, Vassili, Cobat, Aurélie, Zhang, Qian, Casanova, Jean-Laurent, Al-Muhsen, Saleh, Al-Mulla, Fahd, Anderson, Mark S., Andreakos, Evangelos, Arias, Andrés A., Feldman, Hagit Baris, Belot, Alexandre, Biggs, Catherine M., Bogunovic, Dusan, Bondarenko, Anastasiia, Bousfiha, Ahmed A., Bryceson, Yenan, Bustamante, Carlos D., Butte, Manish J., Chakravorty, Samya, Christodoulou, John, Condino-Neto, Antonio, Constantinescu, Stefan N., Cooper, Megan A., Desai, Murkesh, Drolet, Beth A., El Baghdadi, Jamila, Espinosa-Padilla, Sara, Fellay, Jacques, Franco, José Luis, Froidure, Antoine, Gregersen, Peter K., Haerynck, Filomeen, Hagin, David, Halwani, Rabih, Heath, James R., Henrickson, Sarah E., Hsieh, Elena W.Y., Husebye, Eystein, Imai, Kohsuke, Itan, Yuval, Jarvis, Erich D., Karamitros, Timokratis, Kisand, Kai, Ku, Cheng-Lung, Lau, Yu-Lung, Ling, Yun, Lucas, Carrie L., Maniatis, Tom, Maródi, László, Meyts, Isabelle, Milner, Joshua D., Mironska, Kristina, Mogensen, Trine H., Morio, Tomohiro, Ng, Lisa F.P., O'Farrelly, Cliona, Okada, Satoshi, de Diego, Rebeca Perez, Planas, Anna M., Prando, Carolina, Quintana-Murci, Lluis, Renia, Laurent, Resnick, Igor, Rodríguez-Gallego, Carlos, Sancho-Shimizu, Vanessa, Sediva, Anna, Seppänen, Mikko R.J., Shahrooei, Mohammed, Shcherbina, Anna, Slaby, Ondrej, Tancevski, Ivan, Tangye, Stuart G., Abou Tayoun, Ahmad, Ramaswamy, Sathishkumar, Turvey, Stuart E, Uddin, K M Furkan, Uddin, Mohammed J., van de Beek, Diederik, Vinh, Donald C., von Bernuth, Horst, Zatz, Mayana, Zawadzki, Pawel, Foti, Giuseppe, Bellani, Giacomo, Citerio, Giuseppe, Contro, Ernesto, Pesci, Alberto, Valsecchi, Maria Grazia, Cazzaniga, Marina, Abad, Jorge, Accordino, Giulia, Achille, Cristian, Aguilera-Albesa, Sergio, Aguiló-Cucurull, Aina, Özkan, Esra Akyüz, Roblero Albisures, Jonathan Antonio, Aldave, Juan C, Ramos, Miquel Alfonso, Khan, Taj Ali, Aliberti, Anna, Nadji, Seyed Alireza, Alkan, Gulsum, AlKhater, Suzan A., Allardet-Servent, Jerome, Allende, Luis M, Alonso-Arias, Rebeca, Alshahrani, Mohammed S, Alsina, Laia, Alyanakian, Marie-Alexandra, Borrero, Blanca Amador, Amoura, Zahir, Antolí, Arnau, Arrestier, Romain, Aubart, Mélodie, Auguet, Teresa, Avramenko, Iryna, Aytekin, Gökhan, Azot, Axelle, Bahram, Seiamak, Bajolle, Fanny, Baldanti, Fausto, Baldolli, Aurélie, Ballester, Maite, Barrou, Benoit, Barzagh, Federica, Basso, Sabrina, Bayhan, Gulsum Iclal, Bezrodnik, Liliana, Bilbao, Agurtzane, Blanchard-Rohner, Geraldine, Blanco, Ignacio, Blandinières, Adeline, Blázquez-Gamero, Daniel, Bleibtreu, Alexandre, Bloomfield, Marketa, Bolivar-Prados, Mireia, Borghesi, Alessandro, Borie, Raphael, Botdhlo-Nevers, Elisabeth, Bousfiha, Ahmed A, Bousquet, Aurore, Boutolleau, David, Bouvattier, Claire, Boyarchuk, Oksana, Bravais, Juliette, Briones, M. Luisa, Brunner, Marie-Eve, Bruno, Raffaele, Bueno, Maria Rita P, Bukhari, Huda, Cáceres Agra, Juan José, Capra, Ruggero, Carapito, Raphael, Carrabba, Maria, Casasnovas, Carlos, Caseris, Marion, Cassaniti, Irene, Castelle, Martin, Castelli, Francesco, de Vera, Martín Castillo, Castro, Mateus V, Catherinot, Emilie, Celik, Jale Bengi, Ceschi, Alessandro, Chalumeau, Martin, Charbit, Bruno, Cheng, Matthew P., Clavé, Père, Clotet, Bonaventura, Codina, Anna, Cohen, Yves, Comarmond, Cloé, Combes, Alain, Comoli, Patrizia, Corsico, Angelo G, Coşkuner, Taner, Cvetkovski, Aleksandar, Cyrus, Cyril, Dalmau, David, Danion, François, Darley, David Ross, Das, Vincent, Dauby, Nicolas, Dauger, Stéphane, De Munter, Paul, de Pontual, Loic, Dehban, Amin, Delplancq, Geoffroy, Demoule, Alexandre, Desguerre, Isabelle, Di Sabatino, Antonio, Diehl, Jean-Luc, Dobbelaere, Stephanie, Domínguez-Garrido, Elena, Dubost, Clément, Ekwall, Olov, Bozdemir, Şefika Elmas, Elnagdy, Marwa H, Emiroglu, Melike, Endo, Akifumi, Erdeniz, Emine Hafize, Aytekin, Selma Erol, Lasa, Maria Pilar Etxart, Euvrard, Romain, Fabio, Giovanna, Faivre, Laurence, Falck, Antonin, Fartoukh, Muriel, Faure, Morgane, Arquero, Miguel Fernandez, Ferrer, Ricard, Ferreres, Jose, Francois, Bruno, Fumadó, Victoria, Fung, Kitty S C, Fusco, Francesca, Gagro, Alenka, Solis, Blanca Garcia, Gaussem, Pascale, Gayretli, Zeynep, Gil-Herrera, Juana, Gilardin, Laurent, Gatineau, Audrey Giraud, Girona-Alarcón, Mònica, Cifuentes Godínez, Karen Alejandra, Goffard, Jean-Christophe, Gonzales, Nacho, Gonzalez-Granado, Luis I, González-Montelongo, Rafaela, Guerder, Antoine, Gülhan, Belgin, Gumucio, Victor Daniel, Hanitsch, Leif Gunnar, Gunst, Jan, Hadjadj, Jérôme, Hancerli, Selda, Hariyan, Tetyana, Hatipoglu, Nevin, Heppekcan, Deniz, Hernandez-Brito, Elisa, Ho, Po-ki, Holanda-Peña, María Soledad, Horcajada, Juan P, Hraiech, Sami, Humbert, Linda, Hung, Ivan F N, Iglesias, Alejandro D., Íñigo-Campos, Antonio, Jamme, Matthieu, Arranz, María Jesús, Jimeno, Marie-Thérèse, Jordan, Iolanda, Yüksek, Saliha Kanık, Kara, Yalcin Burak, Karahan, Aydın, Karbuz, Adem, Yasar, Kadriye Kart, Kasapcopur, Ozgur, Kashimada, Kenichi, Demirkol, Yasemin Kendir, Kido, Yasutoshi, Kizil, Can, Kılıç, Ahmet Osman, Klocperk, Adam, Koutsoukou, Antonia, Król, Zbigniew J., Ksouri, Hatem, Kuentz, Paul, Kwan, Arthur M C, Kwan, Yat Wah M, Kwok, Janette S Y, Lagier, Jean-Christophe, Lam, David S Y, Lampropoulou, Vicky, Lanternier, Fanny, LAU, Yu-Lung, Le Bourgeois, Fleur, Leo, Yee-Sin, Lopez, Rafael Leon, Leung, Daniel, Levin, Michael, Levy, Michael, Lévy, Romain, Li, Zhi, Lilleri, Daniele, Bolanos Lima, Edson Jose Adrian, Linglart, Agnes, López-Collazo, Eduardo, Lorenzo-Salazar, José M., Louapre, Céline, Lubetzki, Catherine, Lung, Kwok-Cheung, Luyt, Charles-Edouard, Lye, David C, Magnone, Cinthia, Marchioni, Enrico, Marioli, Carola, Marjani, Majid, Marques, Laura, Pereira, Jesus Marquez, Martín-Nalda, Andrea, Pueyo, David Martínez, Martinez-Picado, Javier, Marzana, Iciar, Mata-Martínez, Carmen, Mathian, Alexis, Matos, Larissa RB, Matthews, Gail V, Mayaux, Julien, McLaughlin-Garcia, Raquel, Meersseman, Philippe, Mège, Jean-Louis, Mekontso-Dessap, Armand, Melki, Isabelle, Meloni, Federica, Meritet, Jean-François, Merlani, Paolo, Akcan, Özge Metin, Mezidi, Mehdi, Migeotte, Isabelle, Millereux, Maude, Million, Matthieu, Mirault, Tristan, Mircher, Clotilde, Mirsaeidi, Mehdi, Mizoguchi, Yoko, Modi, Bhavi P, Mojoli, Francesco, Moncomble, Elsa, Melián, Abián Montesdeoca, Martinez, Antonio Morales, Morandeira, Francisco, Morange, Pierre-Emmanuel, Mordacq, Cléemence, Mouly, Stéphane J, Muñoz-Barrera, Adrián, Nafati, Cyril, Nagashima, Shintaro, Nakagama, Yu, Neven, Bénédicte, Neves, João Farela, Ng, Lisa FP, Ng, Yuk-Yung, Nielly, Hubert, Medina, Yeray Novoa, Cuadros, Esmeralda Nuñez, Ocejo-Vinyals, J. Gonzalo, Okamoto, Keisuke, Oualha, Mehdi, Ouedrani, Amani, Özçelik, Tayfun, Ozkaya-Parlakay, Aslinur, Pagani, Michele, Papadaki, Maria, Parizot, Christophe, Parola, Philippe, Pascreau, Tiffany, Paul, Stéphane, Paz-Artal, Estela, Pedraza, Sigifredo, González Pellecer, Nancy Carolina, Pellegrini, Silvia, de Diego, Rebeca Pérez, Pérez-Fernández, Xosé Luis, Philippe, Aurélien, Picod, Adrien, de Chambrun, Marc Pineton, Piralla, Antonio, Ploin, Dominique, Poissy, Julien, Poncelet, Géraldine, Poulakou, Garyphallia, Pouletty, Marie S, Pourshahnazari, Persia, Qiu-Chen, Jia Li, Quentric, Paul, Rambaud, Thomas, Raoult, Didier, Raoult, Violette, Rebillat, Anne-Sophie, Redin, Claire, Resmini, Léa, Ricart, Pilar, Richard, Jean-Christophe, Rigo-Bonnin, Raúl, Rivet, Nadia, Rivière, Jacques G, Rocamora-Blanch, Gemma, Rodero, Mathieu P, Rodrigo, Carlos, Rodriguez, Luis Antonio, Rodriguez-Palmero, Agustí, Romero, Carolina Soledad, Rothenbuhler, Anya, Roux, Damien, Rovina, Nikoletta, Rozenberg, Flore, Ruch, Yvon, Ruiz, Montse, Ruiz del Prado, Maria Yolanda, Ruiz-Rodriguez, Juan Carlos, Sabater-Riera, Joan, Saks, Kai, Salagianni, Maria, Sanchez, Oliver, Sánchez-Montalvá, Adrián, Sánchez-Ramón, Silvia, Schidlowski, Laire, Schluter, Agatha, Schmidt, Julien, Schmidt, Matthieu, Schuetz, Catharina, Schweitzer, Cyril E, Scolari, Francesco, Seijo, Luis, Seminario, Analia Gisela, Sene, Damien, Seng, Piseth, Senoglu, Sevtap, Seppänen, Mikko, Llovich, Alex Serra, Siguret, Virginie, Siouti, Eleni, Smadja, David M, Smith, Nikaia, Sobh, Ali, Solanich, Xavier, Solé-Violán, Jordi, Soler, Catherine, Sözeri, Betül, Stella, Giulia Maria, Stepanovskiy, Yuriy, Stoclin, Annabelle, Taccone, Fabio, Taupin, Jean-Luc, Tavernier, Simon J, Tello, Loreto Vidaur, Terrier, Benjamin, Thiery, Guillaume, Thorball, Christian, Thorn, Karolina, Thumerelle, Caroline, Tipu, Imran, Tolstrup, Martin, Tomasoni, Gabriele, Toubiana, Julie, Alvarez, Josep Trenado, Triantafyllia, Vasiliki, Trouillet-Assant, Sophie, Tsang, Owen T Y, Tserel, Liina, Tso, Eugene Y K, Tucci, Alessandra, Tüter Öz, Şadiye Kübra, Ursini, Matilde Valeria, Utsumi, Takanori, Uzunhan, Yurdagul, Vabres, Pierre, Valencia-Ramos, Juan, Van Den Rym, Ana Maria, Vandernoot, Isabelle, Velez-Santamaria, Valentina, Zuniga Veliz, Silvia Patricia, Vidigal, Mateus C, Viel, Sébastien, Vilain, Cédric, Vilaire-Meunier, Marie E, Villar-García, Judit, Vincent, Audrey, Vogt, Guillaume, Voiriot, Guillaume, Volokha, Alla, Vuotto, Fanny, Wauters, Els, Wauters, Joost, Wu, Alan K L, Wu, Tak-Chiu, Yahşi, Aysun, Yesilbas, Osman, Yildiz, Mehmet, Young, Barnaby E, Yükselmiş, Ufuk, Zecca, Marco, Zuccaro, Valentina, Jens, Van Praet, Lambrecht, Bart N., Eva, Van Braeckel, Cédric, Bosteels, Levi, Hoste, Eric, Hoste, Bauters, Fré, De Clercq, Jozefien, Cathérine, Heijmans, Hans, Slabbynck, Leslie, Naesens, Florkin, Benoit, Boulanger, Cécile, Vanderlinden, Dimitri, Annereau, Jean-Philippe, Briseño-Roa, Luis, Gribouval, Olivier, Pelet, Anna, Andrejak, Claire, Angoulvant, François, Bachelet, Delphine, Bartoli, Marie, Basmaci, Romain, Behilill, Sylvie, Beluze, Marine, Benkerrou, Dehbia, Bhavsar, Krishna, Bouadma, Lila, Bouchez, Sabelline, Bouscambert, Maude, Cervantes-Gonzalez, Minerva, Chair, Anissa, Chirouze, Catherine, Coelho, Alexandra, Couffignal, Camille, Couffin-Cadiergues, Sandrine, d’Ortenzio, Eric, Debray, Marie-Pierre, Deconinck, Lauren, Deplanque, Dominique, Descamps, Diane, Desvallée, Mathilde, Diallo, Alpha, Diouf, Alphonsine, Dorival, Céline, Dubos, François, Duval, Xavier, Elharrar, Brigitte, Eloy, Philippine, Enouf, Vincent, Esperou, Hélène, Esposito-Farese, Marina, Etienne, Manuel, Devouge, Eglantine Ferrand, Gault, Nathalie, Gaymard, Alexandre, Ghosn, Jade, Gigante, Tristan, Gilg, Morgane, Guedj, Jérémie, Hoctin, Alexandre, Hoffmann, Isabelle, Houas, Ikram, Hulot, Jean-Sébastien, Jaafoura, Salma, Kafif, Ouifiya, Kaguelidou, Florentia, Kali, Sabrina, Khalil, Antoine, Khan, Coralie, Laouénan, Cédric, Laribi, Samira, Le, Minh, Le Hingrat, Quentin, Le Mestre, Soizic, Le Nagard, Hervé, Lescure, François-Xavier, Letrou, Sophie, Levy, Yves, Lina, Bruno, Lingas, Guillaume, Lucet, Jean Christophe, Malvy, Denis, Mambert, Marina, Mentré, France, Meziane, Amina, Mouquet, Hugo, Mullaert, Jimmy, Neant, Nadège, Nguyen, Duc, Noret, Marion, Nseir, Saad, Papadopoulos, Aurélie, Paul, Christelle, Peiffer-Smadja, Nathan, Perpoint, Thomas, Petrov-Sanchez, Ventzislava, Peytavin, Gilles, Pham, Huong, Picone, Olivier, Piquard, Valentine, Puéchal, Oriane, Rabaud, Christian, Rosa-Calatrava, Manuel, Rossignol, Bénédicte, Rossignol, Patrick, Roy, Carine, Schneider, Marion, Su, Richa, Tardivon, Coralie, Tellier, Marie-Capucine, Téoulé, François, Terrier, Olivier, Timsit, Jean-François, Tual, Christelle, Van Der Werf, Sylvie, Vanel, Noémie, Veislinger, Aurélie, Visseaux, Benoit, Wiedemann, Aurélie, Yazdanpanah, Yazdan, Alavoine, Loubna, Behillil, Sylvie, Charpentier, Charlotte, Dechanet, Aline, Ecobichon, Jean-Luc, Frezouls, Wahiba, Houhou, Nadhira, Lehacaut, Jonathan, Lucet, Jean-Christophe, Manchon, Pauline, Nouroudine, Mariama, Quintin, Caroline, Thy, Michael, van der Werf, Sylvie, Vignali, Valérie, Chahine, Abir, Waucquier, Nawal, Migaud, Maria-Claire, Djossou, Félix, Mergeay-Fabre, Mayka, Lucarelli, Aude, Demar, Magalie, Bruneau, Léa, Gérardin, Patrick, Maillot, Adrien, Payet, Christine, Laviolle, Bruno, Laine, Fabrice, Paris, Christophe, Desille-Dugast, Mireille, Fouchard, Julie, Pistone, Thierry, Perreau, Pauline, Gissot, Valérie, Le Goas, Carole, Montagne, Samatha, Richard, Lucie, Bouiller, Kévin, Desmarets, Maxime, Meunier, Alexandre, Lefévre, Benjamin, Jeulin, Hélène, Legrand, Karine, Lomazzi, Sandra, Tardy, Bernard, Gagneux-Brunon, Amandine, Bertholon, Frédérique, Botelho-Nevers, Elisabeth, Kouakam, Christelle, Leturque, Nicolas, Roufai, Layidé, Amat, Karine, Espérou, Hélène, Hendou, Samia, van Agtmael, Michiel, Algera, Anne Geke, Appelman, Brent, van Baarle, Frank, Bax, Diane, Beudel, Martijn, Bogaard, Harm Jan, Bomers, Marije, Bonta, Peter, Bos, Lieuwe, Botta, Michela, de Brabander, Justin, de Bree, Godelieve, de Bruin, Sanne, Buis, David T.P., Bugiani, Marianna, Bulle, Esther, Chouchane, Osoul, Cloherty, Alex, Dijkstra, Mirjam, Dongelmans, Dave A., Dujardin, Romein W.G., Elbers, Paul, Fleuren, Lucas, Geerlings, Suzanne, Geijtenbeek, Theo, Girbes, Armand, Goorhuis, Bram, Grobusch, Martin P., Hafkamp, Florianne, Hagens, Laura, Hamann, Jorg, Harris, Vanessa, Hemke, Robert, Hermans, Sabine M., Heunks, Leo, Hollmann, Markus, Horn, Janneke, Hovius, Joppe W., de Jong, Menno D., Koning, Rutger, Lim, Endry H.T., van Mourik, Niels, Nellen, Jeaninne, Nossent, Esther J., Paulus, Frederique, Peters, Edgar, Pina-Fuentes, Dan A.I., van der Poll, Tom, Preckel, Bennedikt, Prins, Jan M., Raasveld, Jorinde, Reijnders, Tom, de Rotte, Maurits C.F.J., Schinkel, Michiel, Schultz, Marcus J., Schrauwen, Femke A.P., Schuurmans, Alex, Schuurmans, Jaap, Sigaloff, Kim, Slim, Marleen A., Smeele, Patrick, Smit, Marry, Stijnis, Cornelis S., Stilma, Willemke, Teunissen, Charlotte, Thoral, Patrick, Tsonas, Anissa M, Tuinman, Pieter R., van der Valk, Marc, Veelo, Denise, Volleman, Carolien, de Vries, Heder, Vught, Lonneke A., van Vugt, Michèle, Wouters, Dorien, Zwinderman, A. H (Koos), Brouwer, Matthijs C., Wiersinga, W. Joost, Vlaar, Alexander P.J., Tompkins, Miranda F., Alba, Camille, Hupalo, Daniel N., Rosenberger, John, Sukumar, Gauthaman, Wilkerson, Matthew D., Zhang, Xijun, Lack, Justin, Oler, Andrew J., Dobbs, Kerry, Delmonte, Ottavia M., Danielson, Jeffrey J., Bettini, Laura Rachele, D’Angio, Mariella, Beretta, Ilaria, Imberti, Luisa, Sottini, Alessandra, Quaresima, Virginia, Quiros-Roldan, Eugenia, Rossi, Camillo, Children's Hospital, HUS Children and Adolescents, Clinicum, Department of Medicine, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, AII - Infectious diseases, ANS - Neuroinfection & -inflammation, Neurology, Infectious diseases, Center of Experimental and Molecular Medicine, APH - Aging & Later Life, APH - Global Health, APH - Quality of Care, AII - Amsterdam institute for Infection and Immunity, APH - Health Behaviors & Chronic Diseases, Global Health, APH - Methodology, Graduate School, ACS - Heart failure & arrhythmias, Anesthesiology, ACS - Diabetes & metabolism, APH - Digital Health, APH - Personalized Medicine, ACS - Microcirculation, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Laboratory of Human Genetics of Infectious Diseases (Necker Branch - INSERM U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Rockefeller University [New York], Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Helix [San Mateo, CA], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Özçelik, Tayfun, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Pathology, Asano, T., Boisson, B., Onodi, F., Matuozzo, D., Moncada-Velez, M., Renkilaraj, M. R. L. M., Zhang, P., Meertens, L., Bolze, A., Materna, M., Korniotis, S., Gervais, A., Talouarn, E., Bigio, B., Seeleuthner, Y., Bilguvar, K., Zhang, Y., Neehus, A. -L., Ogishi, M., Pelham, S. J., Le Voyer, T., Rosain, J., Philippot, Q., Soler-Palacin, P., Colobran, R., Martin-Nalda, A., Riviere, J. G., Tandjaoui-Lambiotte, Y., Chaibi, K., Shahrooei, M., Darazam, I. A., Olyaei, N. A., Mansouri, D., Hatipoglu, N., Palabiyik, F., Ozcelik, T., Novelli, G., Novelli, A., Casari, G., Aiuti, A., Carrera, P., Bondesan, S., Barzaghi, F., Rovere-Querini, P., Tresoldi, C., Franco, J. L., Rojas, J., Reyes, L. F., Bustos, I. G., Arias, A. A., Morelle, G., Kyheng, C., Troya, J., Planas-Serra, L., Schluter, A., Gut, M., Pujol, A., Allende, L. M., Rodriguez-Gallego, C., Flores, C., Cabrera-Marante, O., Pleguezuelo, D. E., Diego, R. P. D., Keles, S., Aytekin, G., Akcan, O. M., Bryceson, Y. T., Bergman, P., Brodin, P., Smole, D., Smith, C. I. E., Norlin, A. -C., Campbell, T. M., Covill, L. E., Hammarstrom, L., Pan-Hammarstrom, Q., Abolhassani, H., Mane, S., Marr, N., Ata, M., Ali, F. A., Khan, T., Spaan, A. N., Dalgard, C. L., Bonfanti, P., Biondi, A., Tubiana, S., Burdet, C., Nussbaum, R., Kahn-Kirby, A., Snow, A. L., Bustamante, J., Puel, A., Boisson-Dupuis, S., Zhang, S. -Y., Beziat, V., Lifton, R. P., Bastard, P., Notarangelo, L. D., Abel, L., Su, H. C., Jouanguy, E., Amara, A., Soumelis, V., Cobat, A., Zhang, Q., Casanova, J. -L., Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, French COVID cohort study group, The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, Rockefeller University, the St. Giles Foundation, the NIH (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at the George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the 'Investments for the Future' program (ANR-10-IAHU-01) and the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project, the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 Research and Innovation Program under grant agreement no. 824110 (EASI-genomics), the Square Foundation, Grandir–Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, Fondation du Souffle, Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the University of Paris. The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). The Neurometabolic Diseases Laboratory received funding from the European Union’s Horizon 2020 Research and Innovation Program (EasiGenomics grant no. 824110 COVID-19/PID12342). A.P., R.P.d.D., C.R.-G., and C.F. were funded by Instituto de Salud Carlos III (COV20_01333 and COV20_01334), the Spanish Ministry of Science and Innovation (RTC-2017-6471-1, AEI/FEDER, UE), Fundación DISA (OA18/017), and Cabildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19'). The laboratories of G.N. and A.N. were supported by a grant awarded to Regione Lazio (PROGETTI DI GRUPPI DI RICERCA 2020) no. A0375-2020-36663, GecoBiomark. A. Amara’s laboratory was supported by ANR under the 'Investments for the Future' program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the FRM (EQU202003010193), ANR (ANR-20-COVI-000 project IDISCOVR and ANR-20-CO11-0004 project FISHBP), and the University of Paris (Plan de Soutien Covid-19: RACPL20FIR01-COVID-SOUL). This work was supported, in part, by the Division of Intramural Research, NIAID, NIH (grants 1ZIAAI001265 to H.C.S. and ZIA AI001270 to L.D.N.). The G.C. laboratory was supported by the Italian Ministry of Health (grant COVID-2020-12371617) and the intramural COVID Host Genetics program. The J.L.F. laboratory was supported, in part, by the Coopération Scientifique France-Colciencias (ECOS-Nord/COLCIENCIAS/MEN/ICETEX, 806-2018) and Colciencias contract 713-2016 (no. 111574455633). The V.S. laboratory was supported by ANR DENDRISEPSIS (ANR-17-CE15-0003) and ANR APCOD (ANR-17-CE15-0003-01), a Fast Grant from the Mercatus Center, FRM, University of Paris PLAN D’URGENCE COVID19. The N.M. laboratory was supported by Sidra Medicine (SDR400048) and the Qatar National Research Fund (grant No. NPRP9-251-3-045). A.-L.N. was supported by the Bettencourt Schueller Foundation and the International PhD program of the Imagine Institute. P. Bergman and C.I.E.S received support from the Center for Medical Innovation (CIMED), the Swedish Medical Research Council and the Stockholm County Council (ALF-project). Part of this work was generated within the European Reference Network for rare primary immunodeficiency, autoinflammatory and autoimmune diseases (RITA)., Members of French COVID Cohort Study Group: Laurent Abel1, Claire Andrejak2, François Angoulvant3, Delphine Bachelet4, Marie Bartoli5, Romain Basmaci6, Sylvie Behilill7, Marine Beluze8, Dehbia Benkerrou9, Krishna Bhavsar4, Lila Bouadma4, Sabelline Bouchez10, Maude Bouscambert11, Minerva Cervantes-Gonzalez4, Anissa Chair4, Catherine Chirouze12, Alexandra Coelho13, Camille Couffignal4, Sandrine Couffin-Cadiergues14, Eric d’Ortenzio5, Marie-Pierre Debray4, Lauren Deconinck4, Dominique Deplanque15, Diane Descamps4, Mathilde Desvallée16, Alpha Diallo5, Alphonsine Diouf13, Céline Dorival9, François Dubos17, Xavier Duval4, Brigitte Elharrar18, Philippine Eloy4, Vincent Enouf7, Hélène Esperou14, Marina Esposito-Farese4, Manuel Etienne19, Eglantine Ferrand Devouge19, Nathalie Gault4, Alexandre Gaymard11, Jade Ghosn4, Tristan Gigante20, Morgane Gilg20, Jérémie Guedj21, Alexandre Hoctin13, Isabelle Hoffmann4, Ikram Houas14, Jean-Sébastien Hulot22, Salma Jaafoura14, Ouifiya Kafif4, Florentia Kaguelidou23, Sabrina Kali4, Antoine Khalil4, Coralie Khan16, Cédric Laouénan4, Samira Laribi4, Minh Le4, Quentin Le Hingrat4, Soizic Le Mestre5, Hervé Le Nagard24, François-Xavier Lescure4, Sophie Letrou4, Yves Levy25, Bruno Lina11, Guillaume Lingas24, Jean Christophe Lucet4, Denis Malvy26, Marina Mambert13, France Mentré4, Amina Meziane9, Hugo Mouquet7, Jimmy Mullaert4, Nadège Neant24, Duc Nguyen26, Marion Noret27, Saad Nseir17, Aurélie Papadopoulos14, Christelle Paul5, Nathan Peiffer-Smadja4, Thomas Perpoint28, Ventzislava Petrov-Sanchez5, Gilles Peytavin4, Huong Pham4, Olivier Picone6, Valentine Piquard4, Oriane Puéchal29, Christian Rabaud30, Manuel Rosa-Calatrava11, Bénédicte Rossignol20, Patrick Rossignol30, Carine Roy4, Marion Schneider4, Richa Su4, Coralie Tardivon4, Marie-Capucine Tellier4, François Téoulé9, Olivier Terrier11, Jean-François Timsit4, Christelle Tual31, Sarah Tubiana4, Sylvie Van Der Werf7, Noémie Vanel32, Aurélie Veislinger31, Benoit Visseaux4, Aurélie Wiedemann25, Yazdan Yazdanpanah4, ANR-17-CE15-0003,DENDRISEPSIS,Analyse systémique des cellules présentatrices d'antigène dans le sepsis humain(2017), ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), Asano, T, Boisson, B, Onodi, F, Matuozzo, D, Moncada-Velez, M, Maglorius Renkilaraj, M, Zhang, P, Meertens, L, Bolze, A, Materna, M, Korniotis, S, Gervais, A, Talouarn, E, Bigio, B, Seeleuthner, Y, Bilguvar, K, Zhang, Y, Neehus, A, Ogishi, M, Pelham, S, Le Voyer, T, Rosain, J, Philippot, Q, Soler-Palacín, P, Colobran, R, Martin-Nalda, A, Rivière, J, Tandjaoui-Lambiotte, Y, Chaïbi, K, Shahrooei, M, Darazam, I, Olyaei, N, Mansouri, D, Hatipoğlu, N, Palabiyik, F, Ozcelik, T, Novelli, G, Novelli, A, Casari, G, Aiuti, A, Carrera, P, Bondesan, S, Barzaghi, F, Rovere-Querini, P, Tresoldi, C, Franco, J, Rojas, J, Reyes, L, Bustos, I, Arias, A, Morelle, G, Christèle, K, Troya, J, Planas-Serra, L, Schlüter, A, Gut, M, Pujol, A, Allende, L, Rodriguez-Gallego, C, Flores, C, Cabrera-Marante, O, Pleguezuelo, D, de Diego, R, Keles, S, Aytekin, G, Akcan, O, Bryceson, Y, Bergman, P, Brodin, P, Smole, D, Smith, C, Norlin, A, Campbell, T, Covill, L, Hammarström, L, Pan-Hammarström, Q, Abolhassani, H, Mane, S, Marr, N, Ata, M, Al Ali, F, Khan, T, Spaan, A, Dalgard, C, Bonfanti, P, Biondi, A, Tubiana, S, Burdet, C, Nussbaum, R, Kahn-Kirby, A, Snow, A, Bustamante, J, Puel, A, Boisson-Dupuis, S, Zhang, S, Béziat, V, Lifton, R, Bastard, P, Notarangelo, L, Abel, L, Su, H, Jouanguy, E, Amara, A, Soumelis, V, Cobat, A, Zhang, Q, and Casanova, J
Subjects: Male, SUBSETS, [SDV]Life Sciences [q-bio], Penetrance, REDUNDANT, COVID-19 (Malaltia), 0302 clinical medicine, Resposta immunitària, 80 and over, Medicine and Health Sciences, Medicine, Young adult, Child, X-linked recessive inheritance, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, 0303 health sciences, education.field_of_study, PYOGENIC BACTERIAL-INFECTIONS, virus diseases, Genetic Diseases, X-Linked, HUMANS, General Medicine, Middle Aged, PROTECTIVE IMMUNITY, 3. Good health, Pedigree, Settore MED/03, Immune System Diseases, Genetic Diseases, Child, Preschool, Cohort, medicine.symptom, SINGLE-STRANDED RNA, Adult, Adolescent, Aged, Alleles, COVID-19, Humans, Infant, Toll-Like Receptor 7, Young Adult, Immunology, Population, Asymptomatic, Article, 03 medical and health sciences, HOST-DEFENSE, Immune response, Allele, Preschool, education, 030304 developmental biology, TOLL-LIKE RECEPTORS, business.industry, RECOGNITION, Proteins, X-Linked, medicine.disease, Pneumonia, 3121 General medicine, internal medicine and other clinical medicine, PLASMACYTOID DENDRITIC CELLS, business, Proteïnes, 030215 immunology
Abstract: Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort of 1,202 male patients aged 0.5 to 99 years (mean: 52.9 years) with unexplained critical COVID-19 pneumonia. None of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean: 38.7 years) tested carry such TLR7 variants (p = 3.5 × 10-5). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (n=2, 5 and 38 years), or moderate (n=1, 5 years), severe (n=1, 27 years), or critical (n=1, 29 years) pneumonia. Two boys (aged 7 and 12 years) from a cohort of 262 male patients with severe COVID-19 pneumonia (mean: 51.0 years) are hemizygous for a deleterious TLR7 variant. The cumulative allele frequency for deleterious TLR7 variants in the male general population is < 6.5x10-4 We also show that blood B cell lines and myeloid cell subsets from the patients do not respond to TLR7 stimulation, a phenotype rescued by wild-type TLR7 The patients' blood plasmacytoid dendritic cells (pDCs) produce low levels of type I IFNs in response to SARS-CoV-2. Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years. Human TLR7 and pDCs are essential for protective type I IFN immunity against SARS-CoV-2 in the respiratory tract. Funding: The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, Rockefeller University; the St. Giles Foundation; the NIH (R01AI088364), the National Center for Advancing Translational Sciences (NCATS); NIH Clinical and Translational Science Award (CTSA) program (UL1TR001866); a Fast Grant from Emergent Ventures; Mercatus Center at the George Mason University; the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956); the Meyer Foundation; the JPB Foundation; the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01) and the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID); the French Foundation for Medical Research (FRM) (EQU201903007798); the FRM and ANR GENCOVID project, the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), and ANR AABIFNCOV (ANR-20-CO11-0001) projects; the European Union’s Horizon 2020 Research and Innovation Program under grant agreement no. 824110 (EASI-genomics). The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). The Neurometabolic Diseases Laboratory received funding from the European Union’s Horizon 2020 Research and Innovation Program (EasiGenomics grant no. 824110 COVID-19/PID12342). A.P., R.P.d.D., C.R.-G., and C.F. were funded by Instituto de Salud Carlos III (COV20_01333 and COV20_01334), the Spanish Ministry of Science and Innovation (RTC-2017-6471-1; AEI/FEDER, UE), Fundación DISA (OA18/017), and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). The laboratories of G.N. and A.N. were supported by a grant awarded to Regione Lazio (PROGETTI DI GRUPPI DI RICERCA 2020) no. A0375-2020-36663, GecoBiomark. A. Amara’s laboratory was supported by ANR under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the FRM (EQU202003010193), ANR (ANR-20-COVI-000 project IDISCOVR and ANR-20-CO11-0004 project FISHBP), and the University of Paris (Plan de Soutien Covid-19: RACPL20FIR01-COVID-SOUL). This work was supported, in part, by the Division of Intramural Research, NIAID, NIH (grants 1ZIAAI001265 to H.C.S. and ZIA AI001270 to L.D.N.). The G.C. laboratory was supported by the Italian Ministry of Health (grant COVID-2020-12371617) and the intramural COVID Host Genetics program. The J.L.F. laboratory was supported, in part, by the Coopération Scientifique France-Colciencias (ECOS-Nord/COLCIENCIAS/MEN/ICETEX; 806-2018) and Colciencias contract 713-2016 (no. 111574455633). The V.S. laboratory was supported by ANR DENDRISEPSIS (ANR-17-CE15-0003) and ANR APCOD (ANR-17-CE15-0003-01), a Fast Grant from the Mercatus Center, FRM, University of Paris PLAN D’URGENCE COVID19. The N.M. laboratory was supported by Sidra Medicine (SDR400048) and the Qatar National Research Fund (grant No. NPRP9-251-3-045)
Published: 2021

26. Association of Variants in the SPTLC1 Gene with Juvenile Amyotrophic Lateral Sclerosis

Author: Johnson, JO, Chia, R, Miller, DE, Li, R, Kumaran, R, Abramzon, Y, Alahmady, N, Renton, AE, Topp, SD, Gibbs, JR, Cookson, MR, Sabir, MS, Dalgard, CL, Troakes, C, Jones, AR, Shatunov, A, Iacoangeli, A, Al Khleifat, A, Ticozzi, N, Silani, V, Gellera, C, Blair, IP, Dobson-Stone, C, Kwok, JB, Bonkowski, ES, Palvadeau, R, Tienari, PJ, Morrison, KE, Shaw, PJ, Al-Chalabi, A, Brown, RH, Calvo, A, Mora, G, Al-Saif, H, Gotkine, M, Leigh, F, Chang, IJ, Perlman, SJ, Glass, I, Scott, AI, Shaw, CE, Basak, AN, Landers, JE, Chiò, A, Crawford, TO, Smith, BN, Traynor, BJ, Fallini, C, Gkazi, AS, Scotter, EL, Kenna, KP, Keagle, P, Tiloca, C, Vance, C, Colombrita, C, King, A, Pensato, V, Castellotti, B, Baas, F, ten Asbroek, ALMA, McKenna-Yasek, D, McLaughlin, RL, Polak, M, Asress, S, Esteban-Pérez, J, Stevic, Z, D’Alfonso, S, Mazzini, L, Comi, GP, Del Bo, R, Ceroni, M, Gagliardi, S, Querin, G, Bertolin, C, van Rheenen, W, Rademakers, R, van Blitterswijk, M, Lauria, G, Duga, S, Corti, S, Cereda, C, Corrado, L, Sorarù, G, Williams, KL, Nicholson, GA, Leblond-Manry, C, Rouleau, GA, Hardiman, O, Veldink, JH, van den Berg, LH, Pall, H, Turner, MR, Talbot, K, Taroni, F, García-Redondo, A, Wu, Z, Glass, JD, Ratti, A, Adeleye, A, Soltis, AR, Alba, C, Viollet, C, Bacikova, D, Hupalo, DN, Sukumar, G, Pollard, HB, Wilkerson, MD, Martinez, EM, Ahmed, S, Arepalli, S, Baloh, RH, Bowser, R, Brady, CB, Brice, A, Broach, J, Campbell, RH, Camu, W, Cooper-Knock, J, Ding, J, Drepper, C, Drory, VE, Dunckley, TL, Eicher, JD, England, BK, Faghri, F, Feldman, E, Floeter, MK, Fratta, P, Geiger, JT, Gerhard, G, Gibson, SB, Hardy, J, Harms, MB, Heiman-Patterson, TD, Hernandez, DG, Jansson, L, Kirby, J, Kowall, NW, Laaksovirta, H, Landeck, N, Landi, F, Le Ber, I, Lumbroso, S, MacGowan, DJL, Maragakis, NJ, Mouzat, K, Murphy, NA, Myllykangas, L, Nalls, MA, Orrell, RW, Ostrow, LW, Pamphlett, R, Pickering-Brown, S, Pioro, EP, Pletnikova, O, Pliner, HA, Pulst, SM, Ravits, JM, Rivera, A, Robberecht, W, Rogaeva, E, Rollinson, S, Rothstein, JD, Scholz, SW, Sendtner, M, Sidle, KC, Simmons, Z, Singleton, AB, Smith, N, Stone, DJ, Troncoso, JC, Valori, M, Van Damme, P, Van Deerlin, VM, Van Den Bosch, L, Zinman, L, Angelocola, SM, Ausiello, FP, Barberis, M, Bartolomei, I, Battistini, S, Bersano, E, Bisogni, G, Borghero, G, Brunetti, M, Cabona, C, Canale, F, Canosa, A, Cantisani, TA, Capasso, M, Caponnetto, C, Cardinali, P, Carrera, P, Casale, F, Colletti, T, Conforti, FL, Conte, A, Conti, E, Corbo, M, Cuccu, S, Dalla Bella, E, D’Errico, E, DeMarco, G, Dubbioso, R, Ferrarese, C, Ferraro, PM, Filippi, M, Fini, N, Floris, G, Fuda, G, Gallone, S, Gianferrari, G, Giannini, F, Grassano, M, Greco, L, Iazzolino, B, Introna, A, La Bella, V, Lattante, S, Liguori, R, Logroscino, G, Logullo, FO, Lunetta, C, Mandich, P, Mandrioli, J, Manera, U, Manganelli, F, Marangi, G, Marinou, K, Marrosu, MG, Martinelli, I, Messina, S, Moglia, C, Mosca, L, Murru, MR, Origone, P, Passaniti, C, Petrelli, C, Petrucci, A, Pozzi, S, Pugliatti, M, Quattrini, A, Ricci, C, Riolo, G, Riva, N, Russo, M, Sabatelli, M, Salamone, P, Salivetto, M, Salvi, F, Santarelli, M, Sbaiz, L, Sideri, R, Simone, I, Simonini, C, Spataro, R, Tanel, R, Tedeschi, G, Ticca, A, Torriello, A, Tranquilli, S, Tremolizzo, L, Trojsi, F, Vasta, R, Vacchiano, V, Vita, G, Volanti, P, Zollino, M, Zucchi, E, Johnson J.O., Chia R., Miller D.E., Li R., Kumaran R., Abramzon Y., Alahmady N., Renton A.E., Topp S.D., Gibbs J.R., Cookson M.R., Sabir M.S., Dalgard C.L., Troakes C., Jones A.R., Shatunov A., Iacoangeli A., Al Khleifat A., Ticozzi N., Silani V., Gellera C., Blair I.P., Dobson-Stone C., Kwok J.B., Bonkowski E.S., Palvadeau R., Tienari P.J., Morrison K.E., Shaw P.J., Al-Chalabi A., Brown R.H., Calvo A., Mora G., Al-Saif H., Gotkine M., Leigh F., Chang I.J., Perlman S.J., Glass I., Scott A.I., Shaw C.E., Basak A.N., Landers J.E., Chio A., Crawford T.O., Smith B.N., Traynor B.J., Fallini C., Gkazi A.S., Scotter E.L., Kenna K.P., Keagle P., Tiloca C., Vance C., Colombrita C., King A., Pensato V., Castellotti B., Baas F., Ten Asbroek A.L.M.A., McKenna-Yasek D., McLaughlin R.L., Polak M., Asress S., Esteban-Perez J., Stevic Z., D'Alfonso S., Mazzini L., Comi G.P., Del Bo R., Ceroni M., Gagliardi S., Querin G., Bertolin C., Van Rheenen W., Rademakers R., Van Blitterswijk M., Lauria G., Duga S., Corti S., Cereda C., Corrado L., Soraru G., Williams K.L., Nicholson G.A., Leblond-Manry C., Rouleau G.A., Hardiman O., Veldink J.H., Van Den Berg L.H., Pall H., Turner M.R., Talbot K., Taroni F., Garcia-Redondo A., Wu Z., Glass J.D., Ratti A., Adeleye A., Soltis A.R., Alba C., Viollet C., Bacikova D., Hupalo D.N., Sukumar G., Pollard H.B., Wilkerson M.D., Martinez E.M., Ahmed S., Arepalli S., Baloh R.H., Bowser R., Brady C.B., Brice A., Broach J., Campbell R.H., Camu W., Cooper-Knock J., Ding J., Drepper C., Drory V.E., Dunckley T.L., Eicher J.D., England B.K., Faghri F., Feldman E., Floeter M.K., Fratta P., Geiger J.T., Gerhard G., Gibson S.B., Hardy J., Harms M.B., Heiman-Patterson T.D., Hernandez D.G., Jansson L., Kirby J., Kowall N.W., Laaksovirta H., Landeck N., Landi F., Le Ber I., Lumbroso S., Macgowan D.J.L., Maragakis N.J., Mouzat K., Murphy N.A., Myllykangas L., Nalls M.A., Orrell R.W., Ostrow L.W., Pamphlett R., Pickering-Brown S., Pioro E.P., Pletnikova O., Pliner H.A., Pulst S.M., Ravits J.M., Rivera A., Robberecht W., Rogaeva E., Rollinson S., Rothstein J.D., Scholz S.W., Sendtner M., Sidle K.C., Simmons Z., Singleton A.B., Smith N., Stone D.J., Troncoso J.C., Valori M., Van Damme P., Van Deerlin V.M., Van Den Bosch L., Zinman L., Angelocola S.M., Ausiello F.P., Barberis M., Bartolomei I., Battistini S., Bersano E., Bisogni G., Borghero G., Brunetti M., Cabona C., Canale F., Canosa A., Cantisani T.A., Capasso M., Caponnetto C., Cardinali P., Carrera P., Casale F., Colletti T., Conforti F.L., Conte A., Conti E., Corbo M., Cuccu S., Dalla Bella E., D'Errico E., Demarco G., Dubbioso R., Ferrarese C., Ferraro P.M., Filippi M., Fini N., Floris G., Fuda G., Gallone S., Gianferrari G., Giannini F., Grassano M., Greco L., Iazzolino B., Introna A., La Bella V., Lattante S., Liguori R., Logroscino G., Logullo F.O., Lunetta C., Mandich P., Mandrioli J., Manera U., Manganelli F., Marangi G., Marinou K., Marrosu M.G., Martinelli I., Messina S., Moglia C., Mosca L., Murru M.R., Origone P., Passaniti C., Petrelli C., Petrucci A., Pozzi S., Pugliatti M., Quattrini A., Ricci C., Riolo G., Riva N., Russo M., Sabatelli M., Salamone P., Salivetto M., Salvi F., Santarelli M., Sbaiz L., Sideri R., Simone I., Simonini C., Spataro R., Tanel R., Tedeschi G., Ticca A., Torriello A., Tranquilli S., Tremolizzo L., Trojsi F., Vasta R., Vacchiano V., Vita G., Volanti P., Zollino M., Zucchi E., Johnson, J. O., Chia, R., Miller, D. E., Li, R., Kumaran, R., Abramzon, Y., Alahmady, N., Renton, A. E., Topp, S. D., Gibbs, J. R., Cookson, M. R., Sabir, M. S., Dalgard, C. L., Troakes, C., Jones, A. R., Shatunov, A., Iacoangeli, A., Al Khleifat, A., Ticozzi, N., Silani, V., Gellera, C., Blair, I. P., Dobson-Stone, C., Kwok, J. B., Bonkowski, E. S., Palvadeau, R., Tienari, P. J., Morrison, K. E., Shaw, P. J., Al-Chalabi, A., Brown, R. H., Calvo, A., Mora, G., Al-Saif, H., Gotkine, M., Leigh, F., Chang, I. J., Perlman, S. J., Glass, I., Scott, A. I., Shaw, C. E., Basak, A. N., Landers, J. E., Chio, A., Crawford, T. O., Smith, B. N., Traynor, B. J., Fallini, C., Gkazi, A. S., Scotter, E. L., Kenna, K. P., Keagle, P., Tiloca, C., Vance, C., Colombrita, C., King, A., Pensato, V., Castellotti, B., Baas, F., Ten Asbroek, A. L. M. A., McKenna-Yasek, D., Mclaughlin, R. L., Polak, M., Asress, S., Esteban-Perez, J., Stevic, Z., D'Alfonso, S., Mazzini, L., Comi, G. P., Del Bo, R., Ceroni, M., Gagliardi, S., Querin, G., Bertolin, C., Van Rheenen, W., Rademakers, R., Van Blitterswijk, M., Lauria, G., Duga, S., Corti, S., Cereda, C., Corrado, L., Soraru, G., Williams, K. L., Nicholson, G. A., Leblond-Manry, C., Rouleau, G. A., Hardiman, O., Veldink, J. H., Van Den Berg, L. H., Pall, H., Turner, M. R., Talbot, K., Taroni, F., Garcia-Redondo, A., Wu, Z., Glass, J. D., Ratti, A., Adeleye, A., Soltis, A. R., Alba, C., Viollet, C., Bacikova, D., Hupalo, D. N., Sukumar, G., Pollard, H. B., Wilkerson, M. D., Martinez, E. M., Ahmed, S., Arepalli, S., Baloh, R. H., Bowser, R., Brady, C. B., Brice, A., Broach, J., Campbell, R. H., Camu, W., Cooper-Knock, J., Ding, J., Drepper, C., Drory, V. E., Dunckley, T. L., Eicher, J. D., England, B. K., Faghri, F., Feldman, E., Floeter, M. K., Fratta, P., Geiger, J. T., Gerhard, G., Gibson, S. B., Hardy, J., Harms, M. B., Heiman-Patterson, T. D., Hernandez, D. G., Jansson, L., Kirby, J., Kowall, N. W., Laaksovirta, H., Landeck, N., Landi, F., Le Ber, I., Lumbroso, S., Macgowan, D. J. L., Maragakis, N. J., Mouzat, K., Murphy, N. A., Myllykangas, L., Nalls, M. A., Orrell, R. W., Ostrow, L. W., Pamphlett, R., Pickering-Brown, S., Pioro, E. P., Pletnikova, O., Pliner, H. A., Pulst, S. M., Ravits, J. M., Rivera, A., Robberecht, W., Rogaeva, E., Rollinson, S., Rothstein, J. D., Scholz, S. W., Sendtner, M., Sidle, K. C., Simmons, Z., Singleton, A. B., Smith, N., Stone, D. J., Troncoso, J. C., Valori, M., Van Damme, P., Van Deerlin, V. M., Van Den Bosch, L., Zinman, L., Angelocola, S. M., Ausiello, F. P., Barberis, M., Bartolomei, I., Battistini, S., Bersano, E., Bisogni, G., Borghero, G., Brunetti, M., Cabona, C., Canale, F., Canosa, A., Cantisani, T. A., Capasso, M., Caponnetto, C., Cardinali, P., Carrera, P., Casale, F., Colletti, T., Conforti, F. L., Conte, A., Conti, E., Corbo, M., Cuccu, S., Dalla Bella, E., D'Errico, E., Demarco, G., Dubbioso, R., Ferrarese, C., Ferraro, P. M., Filippi, M., Fini, N., Floris, G., Fuda, G., Gallone, S., Gianferrari, G., Giannini, F., Grassano, M., Greco, L., Iazzolino, B., Introna, A., La Bella, V., Lattante, S., Liguori, R., Logroscino, G., Logullo, F. O., Lunetta, C., Mandich, P., Mandrioli, J., Manera, U., Manganelli, F., Marangi, G., Marinou, K., Marrosu, M. G., Martinelli, I., Messina, S., Moglia, C., Mosca, L., Murru, M. R., Origone, P., Passaniti, C., Petrelli, C., Petrucci, A., Pozzi, S., Pugliatti, M., Quattrini, A., Ricci, C., Riolo, G., Riva, N., Russo, M., Sabatelli, M., Salamone, P., Salivetto, M., Salvi, F., Santarelli, M., Sbaiz, L., Sideri, R., Simone, I., Simonini, C., Spataro, R., Tanel, R., Tedeschi, G., Ticca, A., Torriello, A., Tranquilli, S., Tremolizzo, L., Trojsi, F., Vasta, R., Vacchiano, V., Vita, G., Volanti, P., Zollino, M., Zucchi, E., Başak, Ayşe Nazlı (ORCID 0000-0001-9257-3540 & YÖK ID 1512), Palvadeau, Robin, Johnson, Janel O., Chia, Ruth, Miller, Danny E., Li, Rachel, Kumaran, Ravindran, Abramzon, Yevgeniya, Alahmady, Nada, Renton, Alan E., Topp, Simon D., Gibbs, J. Raphael, Cookson, Mark R., Sabir, Marya S., Dalgard, Clifton L., Troakes, Claire, Jones, Ashley R., Shatunov, Aleksey, Lacoangeli, Alfredo, Al Khleifat, Ahmad, Ticozzi, Nicola, Silani, Vincenzo, Gellera, Cinzia, Blair, Ian P., Dobson-Stone, Carol, Kwok, John B., Bonkowski, Emily S., Tienari, Pentti J., Morrison, Karen E., Shaw, Pamela J., Al-Chalabi, Ammar, Jr, Robert H. Brown, Calvo, Andrea, Mora, Gabriele, Al-Saif, Hind, Gotkine, Marc, Leigh, Fawn, Chang, Irene J., Perlman, Seth J., Glass, Ian, Scott, Anna, I., Landers, John E., Chio, Adriano, Crawford, Thomas O., Smith, Bradley N., Traynor, Bryan J., Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), School of Medicine, Johnson, J, Chia, R, Miller, D, Li, R, Kumaran, R, Abramzon, Y, Alahmady, N, Renton, A, Topp, S, Gibbs, J, Cookson, M, Sabir, M, Dalgard, C, Troakes, C, Jones, A, Shatunov, A, Iacoangeli, A, Al Khleifat, A, Ticozzi, N, Silani, V, Gellera, C, Blair, I, Dobson-Stone, C, Kwok, J, Bonkowski, E, Palvadeau, R, Tienari, P, Morrison, K, Shaw, P, Al-Chalabi, A, Brown, R, Calvo, A, Mora, G, Al-Saif, H, Gotkine, M, Leigh, F, Chang, I, Perlman, S, Glass, I, Scott, A, Shaw, C, Basak, A, Landers, J, Chiò, A, Crawford, T, Smith, B, Traynor, B, Fallini, C, Gkazi, A, Scotter, E, Kenna, K, Keagle, P, Tiloca, C, Vance, C, Colombrita, C, King, A, Pensato, V, Castellotti, B, Baas, F, Ten Asbroek, A, McKenna-Yasek, D, Mclaughlin, R, Polak, M, Asress, S, Esteban-Pérez, J, Stevic, Z, D'Alfonso, S, Mazzini, L, Comi, G, Del Bo, R, Ceroni, M, Gagliardi, S, Querin, G, Bertolin, C, van Rheenen, W, Rademakers, R, van Blitterswijk, M, Lauria, G, Duga, S, Corti, S, Cereda, C, Corrado, L, Sorarù, G, Williams, K, Nicholson, G, Leblond-Manry, C, Rouleau, G, Hardiman, O, Veldink, J, van den Berg, L, Pall, H, Turner, M, Talbot, K, Taroni, F, García-Redondo, A, Wu, Z, Glass, J, Ratti, A, Adeleye, A, Soltis, A, Alba, C, Viollet, C, Bacikova, D, Hupalo, D, Sukumar, G, Pollard, H, Wilkerson, M, Martinez, E, Ahmed, S, Arepalli, S, Baloh, R, Bowser, R, Brady, C, Brice, A, Broach, J, Campbell, R, Camu, W, Cooper-Knock, J, Ding, J, Drepper, C, Drory, V, Dunckley, T, Eicher, J, England, B, Faghri, F, Feldman, E, Floeter, M, Fratta, P, Geiger, J, Gerhard, G, Gibson, S, Hardy, J, Harms, M, Heiman-Patterson, T, Hernandez, D, Jansson, L, Kirby, J, Kowall, N, Laaksovirta, H, Landeck, N, Landi, F, Le Ber, I, Lumbroso, S, Macgowan, D, Maragakis, N, Mouzat, K, Murphy, N, Myllykangas, L, Nalls, M, Orrell, R, Ostrow, L, Pamphlett, R, Pickering-Brown, S, Pioro, E, Pletnikova, O, Pliner, H, Pulst, S, Ravits, J, Rivera, A, Robberecht, W, Rogaeva, E, Rollinson, S, Rothstein, J, Scholz, S, Sendtner, M, Sidle, K, Simmons, Z, Singleton, A, Smith, N, Stone, D, Troncoso, J, Valori, M, Van Damme, P, Van Deerlin, V, Van Den Bosch, L, Zinman, L, Angelocola, S, Ausiello, F, Barberis, M, Bartolomei, I, Battistini, S, Bersano, E, Bisogni, G, Borghero, G, Brunetti, M, Cabona, C, Canale, F, Canosa, A, Cantisani, T, Capasso, M, Caponnetto, C, Cardinali, P, Carrera, P, Casale, F, Colletti, T, Conforti, F, Conte, A, Conti, E, Corbo, M, Cuccu, S, Dalla Bella, E, D'Errico, E, Demarco, G, Dubbioso, R, Ferrarese, C, Ferraro, P, Filippi, M, Fini, N, Floris, G, Fuda, G, Gallone, S, Gianferrari, G, Giannini, F, Grassano, M, Greco, L, Iazzolino, B, Introna, A, La Bella, V, Lattante, S, Liguori, R, Logroscino, G, Logullo, F, Lunetta, C, Mandich, P, Mandrioli, J, Manera, U, Manganelli, F, Marangi, G, Marinou, K, Marrosu, M, Martinelli, I, Messina, S, Moglia, C, Mosca, L, Murru, M, Origone, P, Passaniti, C, Petrelli, C, Petrucci, A, Pozzi, S, Pugliatti, M, Quattrini, A, Ricci, C, Riolo, G, Riva, N, Russo, M, Sabatelli, M, Salamone, P, Salivetto, M, Salvi, F, Santarelli, M, Sbaiz, L, Sideri, R, Simone, I, Simonini, C, Spataro, R, Tanel, R, Tedeschi, G, Ticca, A, Torriello, A, Tranquilli, S, Tremolizzo, L, Trojsi, F, Vasta, R, Vacchiano, V, Vita, G, Volanti, P, Zollino, M, Zucchi, E, HUS Neurocenter, Department of Neurosciences, Clinicum, Neurologian yksikkö, TRIMM - Translational Immunology Research Program, Pentti Tienari / Principal Investigator, Human Genetics, ARD - Amsterdam Reproduction and Development, ANS - Complex Trait Genetics, Johnson, Janel O, Miller, Danny E, Renton, Alan E, Topp, Simon D, Gibbs, J Raphael, Cookson, Mark R, Sabir, Marya S, Dalgard, Clifton L, Jones, Ashley R, Iacoangeli, Alfredo, Blair, Ian P, Kwok, John B, Bonkowski, Emily S, Tienari, Pentti J, Morrison, Karen E, Shaw, Pamela J, Brown, Robert H, Chang, Irene J, Perlman, Seth J, Scott, Anna I, Shaw, Christopher E, Basak, A Nazli, Landers, John E, Chiò, Adriano, Crawford, Thomas O, Smith, Bradley N, Traynor, Bryan J, Fallini, Claudia, Gkazi, Athina Soragia, Scotter, Emma L, Kenna, Kevin P, Keagle, Pamela, Tiloca, Cinzia, Vance, Caroline, Colombrita, Claudia, King, Andrew, Pensato, Viviana, Castellotti, Barbara, Baas, Frank, Ten Asbroek, Anneloor L M A, McKenna-Yasek, Diane, Mclaughlin, Russell L, Polak, Meraida, Asress, Seneshaw, Esteban-Pérez, Jesú, Stevic, Zorica, D'Alfonso, Sandra, Mazzini, Letizia, Comi, Giacomo P, Del Bo, Roberto, Ceroni, Mauro, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, van Rheenen, Wouter, Rademakers, Rosa, van Blitterswijk, Marka, Lauria, Giuseppe, Duga, Stefano, Corti, Stefania, Cereda, Cristina, Corrado, Lucia, Sorarù, Gianni, Williams, Kelly L, Nicholson, Garth A, Leblond-Manry, Claire, Rouleau, Guy A, Hardiman, Orla, Veldink, Jan H, van den Berg, Leonard H, Pall, Hardev, Turner, Martin R, Talbot, Kevin, Taroni, Franco, García-Redondo, Alberto, Wu, Zheyang, Glass, Jonathan D, Ratti, Antonia, Adeleye, Adelani, Soltis, Anthony R, Alba, Camille, Viollet, Coralie, Bacikova, Dagmar, Hupalo, Daniel N, Sukumar, Gauthaman, Pollard, Harvey B, Wilkerson, Matthew D, Martinez, Elisa McGrath, Ahmed, Sarah, Arepalli, Sampath, Baloh, Robert H, Bowser, Robert, Brady, Christopher B, Brice, Alexi, Broach, Jame, Campbell, Roy H, Camu, William, Cooper-Knock, John, Ding, Jinhui, Drepper, Carsten, Drory, Vivian E, Dunckley, Travis L, Eicher, John D, England, Bryce K, Faghri, Faraz, Feldman, Eva, Floeter, Mary Kay, Fratta, Pietro, Geiger, Joshua T, Gerhard, Glenn, Gibson, Summer B, Hardy, John, Harms, Matthew B, Heiman-Patterson, Terry D, Hernandez, Dena G, Jansson, Lilja, Kirby, Janine, Kowall, Neil W, Laaksovirta, Hannu, Landeck, Natalie, Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, Macgowan, Daniel J L, Maragakis, Nicholas J, Mouzat, Kevin, Murphy, Natalie A, Myllykangas, Liisa, Nalls, Mike A, Orrell, Richard W, Ostrow, Lyle W, Pamphlett, Roger, Pickering-Brown, Stuart, Pioro, Erik P, Pletnikova, Olga, Pliner, Hannah A, Pulst, Stefan M, Ravits, John M, Rivera, Alberto, Robberecht, Wim, Rogaeva, Ekaterina, Rollinson, Sara, Rothstein, Jeffrey D, Scholz, Sonja W, Sendtner, Michael, Sidle, Katie C, Simmons, Zachary, Singleton, Andrew B, Smith, Nathan, Stone, David J, Troncoso, Juan C, Valori, Miko, Van Damme, Philip, Van Deerlin, Vivianna M, Van Den Bosch, Ludo, Zinman, Lorne, Angelocola, Stefania M, Ausiello, Francesco P, Barberis, Marco, Bartolomei, Ilaria, Battistini, Stefania, Bersano, Enrica, Bisogni, Giulia, Borghero, Giuseppe, Brunetti, Maura, Cabona, Corrado, Canale, Fabrizio, Canosa, Antonio, Cantisani, Teresa A, Capasso, Margherita, Caponnetto, Claudia, Cardinali, Patrizio, Carrera, Paola, Casale, Federico, Colletti, Tiziana, Conforti, Francesca L, Conte, Amelia, Conti, Elisa, Corbo, Massimo, Cuccu, Stefania, Dalla Bella, Eleonora, D'Errico, Eustachio, Demarco, Giovanni, Dubbioso, Raffaele, Ferrarese, Carlo, Ferraro, Pilar M, Filippi, Massimo, Fini, Nicola, Floris, Gianluca, Fuda, Giuseppe, Gallone, Salvatore, Gianferrari, Giulia, Giannini, Fabio, Grassano, Maurizio, Greco, Lucia, Iazzolino, Barbara, Introna, Alessandro, La Bella, Vincenzo, Lattante, Serena, Liguori, Rocco, Logroscino, Giancarlo, Logullo, Francesco O, Lunetta, Christian, Mandich, Paola, Mandrioli, Jessica, Manera, Umberto, Manganelli, Fiore, Marangi, Giuseppe, Marinou, Kalliopi, Marrosu, Maria Giovanna, Martinelli, Ilaria, Messina, Sonia, Moglia, Cristina, Mosca, Lorena, Murru, Maria R, Origone, Paola, Passaniti, Carla, Petrelli, Cristina, Petrucci, Antonio, Pozzi, Susanna, Pugliatti, Maura, Quattrini, Angelo, Ricci, Claudia, Riolo, Giulia, Riva, Nilo, Russo, Massimo, Sabatelli, Mario, Salamone, Paolina, Salivetto, Marco, Salvi, Fabrizio, Santarelli, Marialuisa, Sbaiz, Luca, Sideri, Riccardo, Simone, Isabella, Simonini, Cecilia, Spataro, Rossella, Tanel, Raffaella, Tedeschi, Gioacchino, Ticca, Anna, Torriello, Antonella, Tranquilli, Stefania, Tremolizzo, Lucio, Trojsi, Francesca, Vasta, Rosario, Vacchiano, Veria, Vita, Giuseppe, Volanti, Paolo, Zollino, Marcella, and Zucchi, Elisabetta
Subjects: Hereditary sensory neuropathy, L-serine, Mutations, Deoxysphingolipids, Accumulation, Enzyme complex, Juvenile amyotrophic lateral sclerosis, Serine C-Palmitoyltransferase, Whole Exome Sequencing, 0302 clinical medicine, Medicine, Family history, Amyotrophic lateral sclerosis, Child, Index case, Exome sequencing, Original Investigation, 0303 health sciences, Neurosciences and neurology, 3. Good health, Child, Preschool, Failure to thrive, Female, medicine.symptom, Life Sciences & Biomedicine, L-SERINE, Comments, Human, Adult, medicine.medical_specialty, Adolescent, Amyotrophic Lateral Sclerosis, Genetic Predisposition to Disease, Humans, Mutation, Young Adult, Clinical Neurology, NO, 03 medical and health sciences, DEOXYSPHINGOLIPIDS, Internal medicine, Exome Sequencing, Online First, Juvenile, Preschool, 030304 developmental biology, ACCUMULATION, Science & Technology, SPTLC1, business.industry, MUTATIONS, Research, 3112 Neurosciences, medicine.disease, HEREDITARY SENSORY NEUROPATHY, juvenile, 3111 Biomedicine, Neurology (clinical), Neurosciences & Neurology, ALS, genetic, business, 030217 neurology & neurosurgery, Amyotrophic Lateral Sclerosi
Abstract: Key Points Question What genetic variants are associated with juvenile amyotrophic lateral sclerosis (ALS)? Findings In this family-based genetic study, exome sequencing was performed in 3 patients diagnosed with juvenile ALS and failure to thrive; this identified de novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient). Variants in SPTLC1 are a known cause of hereditary sensory and autonomic neuropathy, type 1A, and these data extend the phenotype associated with this gene. Meaning De novo variants in the SPTLC1 gene are associated with juvenile ALS, a fatal neurological disorder., This genetic association study identifies genetic variants associated with juvenile amyotrophic lateral sclerosis., Importance Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation. Objective To identify the genetic variants associated with juvenile ALS. Design, Setting, and Participants In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism. Main Outcomes and Measures De novo variants present only in the index case and not in unaffected family members. Results Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway. Conclusions and Relevance These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.
Published: 2021

27. Clonal hematopoiesis is not significantly associated with COVID-19 disease severity

Author: Yifan Zhou, Ruba Shalhoub, Stephanie N. Rogers, Shiqin Yu, Muxin Gu, Margarete A. Fabre, Pedro M. Quiros, Tae-Hoon Shin, Arch Diangson, Wenhan Deng, Shubha Anand, Wenhua Lu, Matthew Cullen, Anna L. Godfrey, Jacobus Preller, Jerome Hadjadj, Emmanuelle Jouanguy, Aurélie Cobat, Laurent Abel, Frederic Rieux-Laucat, Benjamin Terrier, Alain Fischer, Lara Novik, Ingelise J. Gordon, Larisa Strom, Martin R. Gaudinski, Andrea Lisco, Irini Sereti, Thomas J. Gniadek, Andrea Biondi, Paolo Bonfanti, Luisa Imberti, Clifton L. Dalgard, Yu Zhang, Kerry Dobbs, Helen C. Su, Luigi D. Notarangelo, Colin O. Wu, Peter J.M. Openshaw, Malcolm G. Semple, Ziad Mallat, Kenneth Baillie, Cynthia E. Dunbar, George S. Vassiliou, Zhou, Yifan [0000-0002-3538-621X], Rogers, Stephanie N [0000-0002-4563-1899], Gu, Muxin [0000-0003-4376-795X], Fabre, Margarete A [0000-0001-7794-610X], Quiros, Pedro M [0000-0002-7793-6291], Shin, Tae-Hoon [0000-0002-9619-8554], Preller, Jacobus [0000-0001-5706-816X], Cobat, Aurélie [0000-0001-7209-6257], Rieux-Laucat, Frederic [0000-0001-7858-7866], Gaudinski, Martin R [0000-0002-3743-5281], Biondi, Andrea [0000-0002-6757-6173], Bonfanti, Paolo [0000-0001-7289-8823], Imberti, Luisa [0000-0002-2075-8391], Dobbs, Kerry [0000-0002-3432-3137], Notarangelo, Luigi D [0000-0002-8335-0262], Openshaw, Peter JM [0000-0002-7220-2555], Semple, Malcolm G [0000-0001-9700-0418], Mallat, Ziad [0000-0003-0443-7878], Baillie, Kenneth [0000-0001-5258-793X], Dunbar, Cynthia E [0000-0002-7645-838X], Vassiliou, George S [0000-0003-4337-8022], Apollo - University of Cambridge Repository, Zhou, Y, Shalhoub, R, Rogers, S, Yu, S, Gu, M, Fabre, M, Quiros, P, Diangson, A, Deng, W, Anand, S, Lu, W, Cullen, M, Godfrey, A, Preller, J, Hadjadj, J, Jouanguy, E, Cobat, A, Abel, L, Rieux-Laucat, F, Terrier, B, Fischer, A, Novik, L, Gordon, I, Strom, L, Gaudinski, M, Lisco, A, Sereti, I, Gniadek, T, Biondi, A, Bonfanti, P, Imberti, L, Zhang, Y, Dalgard, C, Dobbs, K, Su, H, Notarangelo, L, Wu, C, Openshaw, P, Semple, M, Mallat, Z, Baillie, K, Dunbar, C, and Vassiliou, G
Subjects: Clonal Evolution, Immunology, Mutation, COVID-19, Humans, Cell Biology, Hematology, Clonal Hematopoiesis, Biochemistry, Severity of Illness Index, Hematopoiesis
Abstract: Clonal hematopoiesis (CH) describes the disproportionate expansion of a hematopoietic stemcell (HSC) and its progeny, in association with leukemia-associated somatic mutations, mostcommonly affecting the genes for epigenetic regulators DNMT3A, TET2 and ASXL1.The prevalence and size of such clones rise with age, in association with changes in the driver gene landscape.10 CH is associated with an increased risk of hematologic malignancies, but also of cardiovascular disease (CVD), independently of other known CVD risk factors.11,12 The basis forthis increased CVD risk has been linked to hyperinflammatory positive feedback loops driven by increased cytokine release from clonal myeloid cells, particularly interleukin IL-6 and IL-1β.
Published: 2022

28. Multicenter analysis of neutrophil extracellular trap dysregulation in adult and pediatric COVID-19

Author: Carmelo Carmona-Rivera, Yu Zhang, Kerry Dobbs, Tovah E. Markowitz, Clifton L. Dalgard, Andrew J. Oler, Dillon R. Claybaugh, Deborah Draper, Meng Truong, Ottavia M. Delmonte, Francesco Licciardi, Ugo Ramenghi, Nicoletta Crescenzio, Luisa Imberti, Alessandra Sottini, Virginia Quaresima, Chiara Fiorini, Valentina Discepolo, Andrea Lo Vecchio, Alfredo Guarino, Luca Pierri, Andrea Catzola, Andrea Biondi, Paolo Bonfanti, Maria C. Poli Harlowe, Yasmin Espinosa, Camila Astudillo, Emma Rey-Jurado, Cecilia Vial, Javiera de la Cruz, Ricardo Gonzalez, Cecilia Pinera, Jacqueline W. Mays, Ashley Ng, Andrew Platt, Beth Drolet, John Moon, Edward W. Cowen, Heather Kenney, Sarah E. Weber, Riccardo Castagnoli, Mary Magliocco, Michael A. Stack, Gina Montealegre, Karyl Barron, Danielle L. Fink, Douglas B. Kuhns, Stephen M. Hewitt, Lisa M. Arkin, Daniel S. Chertow, Helen C. Su, Luigi D. Notarangelo, Mariana J. Kaplan, Carmona-Rivera, C, Zhang, Y, Dobbs, K, Markowitz, T, Dalgard, C, Oler, A, Claybaugh, D, Draper, D, Truong, M, Delmonte, O, Licciardi, F, Ramenghi, U, Crescenzio, N, Imberti, L, Sottini, A, Quaresima, V, Fiorini, C, Discepolo, V, Lo Vecchio, A, Guarino, A, Pierri, L, Catzola, A, Biondi, A, Bonfanti, P, Poli Harlowe, M, Espinosa, Y, Astudillo, C, Rey-Jurado, E, Vial, C, De la Cruz, J, Gonzalez, R, Pinera, C, Mays, J, Ng, A, Platt, A, Drolet, B, Moon, J, Cowen, E, Kenney, H, Weber, S, Castagnoli, R, Magliocco, M, Stack, M, Montealegre Sanchez, G, Barron, K, Fink, D, Kuhns, D, Hewitt, S, Arkin, L, Chertow, D, Su, H, Notarangelo, L, Kaplan, M, Carmona-Rivera, Carmelo, Zhang, Yu, Dobbs, Kerry, Markowitz, Tovah E, Dalgard, Clifton L, Oler, Andrew J, Claybaugh, Dillon R, Draper, Deborah, Truong, Meng, Delmonte, Ottavia M, Licciardi, Francesco, Ramenghi, Ugo, Crescenzio, Nicoletta, Imberti, Luisa, Sottini, Alessandra, Quaresima, Virginia, Fiorini, Chiara, Discepolo, Valentina, Lo Vecchio, Andrea, Guarino, Alfredo, Pierri, Luca, Catzola, Andrea, Biondi, Andrea, Bonfanti, Paolo, Poli Harlowe, Maria C, Espinosa, Yasmin, Astudillo, Camila, Rey-Jurado, Emma, Vial, Cecilia, de la Cruz, Javiera, Gonzalez, Ricardo, Pinera, Cecilia, Mays, Jacqueline W, Ng, Ashley, Platt, Andrew, Drolet, Beth, Moon, John, Cowen, Edward W, Kenney, Heather, Weber, Sarah E, Castagnoli, Riccardo, Magliocco, Mary, Stack, Michael A, Montealegre, Gina, Barron, Karyl, Fink, Danielle L, Kuhns, Douglas B, Hewitt, Stephen M, Arkin, Lisa M, Chertow, Daniel S, Su, Helen C, Notarangelo, Luigi D, and Kaplan, Mariana J
Subjects: Adult, Inflammation, Infectious disease, Neutrophils, SARS-CoV-2, Neutrophil, COVID-19, General Medicine, Actins, Child, Deoxyribonuclease I, Humans, Systemic Inflammatory Response Syndrome, Extracellular Traps
Abstract: Dysregulation in neutrophil extracellular trap (NET) formation and degradation may play a role in the pathogenesis and severity of COVID-19; however, its role in the pediatric manifestations of this disease including MIS-C and chilblain-like lesions (CLL), otherwise known as “COVID toes”, remains unclear. Studying multinational cohorts, we found that, in CLL, NETs were significantly increased in serum and skin. There was geographic variability in the prevalence of increased NETs in MIS-C, in association with disease severity. MIS-C and CLL serum samples displayed decreased NET degradation ability, in association with C1q and G-actin or anti-NET antibodies, respectively, but not with genetic variants of DNases. In adult COVID-19, persistent elevations in NETs post-disease diagnosis were detected but did not occur in asymptomatic infection. COVID-19-affected adults displayed significant prevalence of impaired NET degradation, in association with anti-DNase1L3, G-actin, and specific disease manifestations, but not with genetic variants of DNases. NETs were detected in many organs of adult patients who died from COVID-19 complications. Infection with the Omicron variant was associated with decreased levels of NETs when compared to other SARS-CoV-2 strains. These data support a role for NETs in the pathogenesis and severity of COVID-19 in pediatric and adult patients.SummaryNET formation and degradation are dysregulated in pediatric and symptomatic adult patients with various complications of COVID-19, in association with disease severity. NET degradation impairments are multifactorial and associated with natural inhibitors of DNase 1, G-actin and anti-DNase1L3 and anti-NET antibodies. Infection with the Omicron variant is associated with decreased levels of NETs when compared to other SARS-CoV-2 strains.
Published: 2022

29. Human genetic and immunological determinants of critical COVID-19 pneumonia

Author: Zhang, Qian, Bastard, Paul, Karbuz, Adem, Gervais, Adrian, Tayoun, Ahmad Abou, Aiuti, Alessandro, Belot, Alexandre, Bolze, Alexandre, Gaudet, Alexandre, Bondarenko, Anastasiia, Liu, Zhiyong, Spaan, András, Guennoun, Andrea, Arias, Andres Augusto, Planas, Anna, Sediva, Anna, Shcherbina, Anna, Neehus, Anna-Lena, Puel, Anne, Froidure, Antoine, Novelli, Antonio, Parlakay, Aslınur Özkaya, Pujol, Aurora, Yahşi, Aysun, Gülhan, Belgin, Bigio, Benedetta, Boisson, Bertrand, Drolet, Beth, Franco, Carlos Andres Arango, Flores, Carlos, Rodríguez-Gallego, Carlos, Prando, Carolina, Biggs, Catherine, Luyt, Charles-Edouard, Dalgard, Clifton, O’Farrelly, Cliona, Matuozzo, Daniela, Dalmau, David, Perlin, David, Mansouri, Davood, van de Beek, Diederik, Vinh, Donald, Dominguez-Garrido, Elena, Hsieh, Elena, Erdeniz, Emine Hafize, Jouanguy, Emmanuelle, Şevketoglu, Esra, Talouarn, Estelle, Quiros-Roldan, Eugenia, Andreakos, Evangelos, Husebye, Eystein, Alsohime, Fahad, Haerynck, Filomeen, Casari, Giorgio, Novelli, Giuseppe, Aytekin, Gökhan, Morelle, Guillaume, Alkan, Gulsum, Bayhan, Gulsum Iclal, Feldman, Hagit Baris, Su, Helen, von Bernuth, Horst, Resnick, Igor, Bustos, Ingrid, Meyts, Isabelle, Migeotte, Isabelle, Tancevski, Ivan, Bustamante, Jacinta, Fellay, Jacques, El Baghdadi, Jamila, Martinez-Picado, Javier, Casanova, Jean-Laurent, Rosain, Jeremie, Manry, Jeremy, Chen, Jie, Christodoulou, John, Bohlen, Jonathan, Franco, José Luis, Li, Juan, Anaya, Juan Manuel, Rojas, Julian, Ye, Junqiang, Uddin, K., Yasar, Kadriye Kart, Kisand, Kai, Okamoto, Keisuke, Chaïbi, Khalil, Mironska, Kristina, Maródi, László, Abel, Laurent, Renia, Laurent, Lorenzo, Lazaro, Hammarström, Lennart, Ng, Lisa, Quintana-Murci, Lluis, Erazo, Lucia Victoria, Notarangelo, Luigi, Reyes, Luis Felipe, Allende, Luis, Imberti, Luisa, Renkilaraj, Majistor Raj Luxman Maglorius, Moncada-Velez, Marcela, Materna, Marie, Anderson, Mark, Gut, Marta, Chbihi, Marwa, Ogishi, Masato, Emiroglu, Melike, Seppänen, Mikko, Uddin, Mohammed, Shahrooei, Mohammed, Alexander, Natalie, Hatipoglu, Nevin, Marr, Nico, Akçay, Nihal, Boyarchuk, Oksana, Slaby, Ondrej, Akcan, Ozge Metin, Zhang, Peng, Soler-Palacín, Pere, Gregersen, Peter, Brodin, Petter, Garçon, Pierre, Morange, Pierre-Emmanuel, Pan-Hammarström, Qiang, Zhou, Qinhua, Philippot, Quentin, Halwani, Rabih, de Diego, Rebeca Perez, Levy, Romain, Yang, Rui, Öz, Şadiye Kübra Tüter, Muhsen, Saleh Al, Kanık-Yüksek, Saliha, Espinosa-Padilla, Sara, Ramaswamy, Sathishkumar, Okada, Satoshi, Bozdemir, Sefika Elmas, Aytekin, Selma Erol, Karabela, Şemsi Nur, Keles, Sevgi, Senoglu, Sevtap, Zhang, Shen-Ying, Duvlis, Sotirija, Constantinescu, Stefan, Boisson-Dupuis, Stephanie, Turvey, Stuart, Tangye, Stuart, Asano, Takaki, Ozcelik, Tayfun, Le Voyer, Tom, Maniatis, Tom, Morio, Tomohiro, Mogensen, Trine, Sancho-Shimizu, Vanessa, Beziat, Vivien, Solanich, Xavier, Bryceson, Yenan, Lau, Yu-Lung, Itan, Yuval, Cobat, Aurélie, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, Effort, COVID Human Genetic, Özçelik, Tayfun, Howard Hughes Medical Institute, Rockefeller University, St. Giles Foundation, National Institutes of Health (US), National Center for Advancing Translational Sciences (US), George Mason University, National Human Genome Research Institute (US), Yale University, Fisher Center for Alzheimer's Research Foundation, Meyer Foundation, JPB Foundation, Agence Nationale de la Recherche (France), Fondation pour la Recherche Médicale, European Commission, Square Foundation, Ministère de l’Enseignement supérieur et de la Recherche (France), Institut National de la Santé et de la Recherche Médicale (France), Université de Paris, Fondation Bettencourt Schueller, Regione Lazio, National Institute of Allergy and Infectious Diseases (US), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), ANR-20-COV6-0001,CRISPR-TARGET-CoV,Cribles CRISPR à l'échelle du génome pour identifier de nouvelles cibles thérapeutiques et inhiber la réplication du SARS-CoV-2(2020), Zhang, Q., Bastard, P., Karbuz, A., Gervais, A., Tayoun, A. A., Aiuti, A., Belot, A., Bolze, A., Gaudet, A., Bondarenko, A., Spaan, A. N., Guennoun, A., Arias, A. A., Planas, A. M., Sediva, A., Shcherbina, A., Neehus, A. -L., Puel, A., Froidure, A., Novelli, A., Parlakay, A. O., Pujol, A., Yahsi, A., Gulhan, B., Bigio, B., Boisson, B., Drolet, B. A., Franco, C. A. A., Flores, C., Rodriguez-Gallego, C., Prando, C., Biggs, C. M., Luyt, C. -E., Dalgard, C. L., O'Farrelly, C., Matuozzo, D., Dalmau, D., Perlin, D. S., Mansouri, D., van de Beek, D., Vinh, D. C., Dominguez-Garrido, E., Hsieh, E. W. Y., Erdeniz, E. H., Jouanguy, E., Sevketoglu, E., Talouarn, E., Quiros-Roldan, E., Andreakos, E., Husebye, E., Alsohime, F., Haerynck, F., Casari, G., Novelli, G., Aytekin, G., Morelle, G., Alkan, G., Bayhan, G. I., Feldman, H. B., Su, H. C., von Bernuth, H., Resnick, I., Bustos, I., Meyts, I., Migeotte, I., Tancevski, I., Bustamantem, J., Fellay, J., El Baghdadi, J., Martinez-Picado, J., Casanova, J. -L., Rosain, J., Manry, J., Chen, J., Christodoulou, J., Bohlen, J., Franco, J. L., Li, J., Anaya, J. M., Rojas, J., Ye, J., Uddin, K. M. F., Yasar, K. K., Kisand, K., Okamoto, K., Chaibi, K., Mironska, K., Marodi, L., Abel, L., Renia, L., Lorenzo, L., Hammarstrom, L., Ng, L. F. P., Quintana-Murci, L., Erazo, L. V., Notarangelo, L. D., Reyes, L. F., Allende, L. M., Imberti, L., Renkilaraj, M. R. L. M., Moncada-Velez, M., Materna, M., Anderson, M. S., Gut, M., Chbihi, M., Ogishi, M., Emiroglu, M., Seppanen, M. R. J., Uddin, M. J., Shahrooei, M., Alexander, N., Hatipoglu, N., Marr, N., Akcay, N., Boyarchuk, O., Slaby, O., Akcan, O. M., Zhang, P., Soler-Palacin, P., Gregersen, P. K., Brodin, P., Garcon, P., Morange, P. -E., Pan-Hammarstrom, Q., Zhou, Q., Philippot, Q., Halwani, R., de Diego, R. P., Levy, R., Yang, R., Oz, S. K. T., Muhsen, S. A., Kanik-Yuksek, S., Espinosa-Padilla, S., Ramaswamy, S., Okada, S., Bozdemir, S. E., Aytekin, S. E., Karabela, S. N., Keles, S., Senoglu, S., Zhang, S. -Y., Duvlis, S., Constantinescu, S. N., Boisson-Dupuis, S., Turvey, S. E., Tangye, S. G., Asano, T., Ozcelik, T., Le Voyer, T., Maniatis, T., Morio, T., Mogensen, T. H., Sancho-Shimizu, V., Beziat, V., Solanich, X., Bryceson, Y., Lau, Y. -L., Itan, Y., and Cobat, A.
Subjects: Multidisciplinary, [SDV]Life Sciences [q-bio], Critical Illness, COVID-19, Dendritic Cells, Article, Toll-Like Receptor 3, Basic medicine, Age Distribution, Toll-Like Receptor 7, Settore MED/03, Interferon Type I, Humans, Autoantibodies, Genome-Wide Association Study, Sex Distribution
Abstract: COVID Human Genetic Effort: Adem Karbuz, Adrian Gervais, Ahmad Abou Tayoun, Alessandro Aiuti, Alexandre Belot, Alexandre Bolze, Alexandre Gaudet, Anastasiia Bondarenko, Zhiyong Liu, András N. Spaan, Andrea Guennoun, Andres Augusto Arias, Anna M. Planas, Anna Sediva, Anna Shcherbina, Anna-Lena Neehus, Anne Puel, Antoine Froidure, Antonio Novelli, Aslınur Özkaya Parlakay, Aurora Pujol, Aysun Yahşi, Belgin Gülhan, Benedetta Bigio, Bertrand Boisson, Beth A. Drolet, Carlos Andres Arango Franco, Carlos Flores, Carlos Rodríguez-Gallego, Carolina Prando, Catherine M. Biggs, Charles-Edouard Luyt, Clifton L. Dalgard, Cliona O’Farrelly, Daniela Matuozzo, David Dalmau, David S. Perlin, Davood Mansouri, Diederik van de Beek, Donald C. Vinh, Elena Dominguez-Garrido, Elena W. Y. Hsieh, Emine Hafize Erdeniz, Emmanuelle Jouanguy, Esra Şevketoglu, Estelle Talouarn, Eugenia Quiros-Roldan, Evangelos Andreakos, Eystein Husebye, Fahad Alsohime, Filomeen Haerynck, Giorgio Casari, Giuseppe Novelli, Gökhan Aytekin, Guillaume Morelle, Gulsum Alkan, Gulsum Iclal Bayhan, Hagit Baris Feldman, Helen C. Su, Horst von Bernuth, Igor Resnick, Ingrid Bustos, Isabelle Meyts, Isabelle Migeotte, Ivan Tancevski, Jacinta Bustamante, Jacques Fellay, Jamila El Baghdadi, Javier Martinez-Picado, Jean-Laurent Casanova, Jeremie Rosain, Jeremy Manry, Jie Chen, John Christodoulou, Jonathan Bohlen, José Luis Franco, Juan Li, Juan Manuel Anaya, Julian Rojas, Junqiang Ye, K. M. Furkan Uddin, Kadriye Kart Yasar, Kai Kisand, Keisuke Okamoto, Khalil Chaïbi, Kristina Mironska, László Maródi, Laurent Abel, Laurent Renia, Lazaro Lorenzo, Lennart Hammarström, Lisa F. P. Ng, Lluis Quintana-Murci, Lucia Victoria Erazo, Luigi D. Notarangelo, Luis Felipe Reyes, Luis M. Allende, Luisa Imberti, Majistor Raj Luxman Maglorius Renkilaraj, Marcela Moncada-Velez, Marie Materna, Mark S. Anderson, Marta Gut, Marwa Chbihi, Masato Ogishi, Melike Emiroglu, Mikko R. J. Seppänen, Mohammed J. Uddin, Mohammed Shahrooei, Natalie Alexander, Nevin Hatipoglu, Nico Marr, Nihal Akçay, Oksana Boyarchuk, Ondrej Slaby, Ozge Metin Akcan, Peng Zhang, Pere Soler-Palacín, Peter K. Gregersen, Petter Brodin, Pierre Garçon, Pierre-Emmanuel Morange, Qiang Pan-Hammarström, Qinhua Zhou, Quentin Philippot, Rabih Halwani, Rebeca Perez de Diego, Romain Levy, Rui Yang, Şadiye Kübra Tüter Öz, Saleh Al Muhsen, Saliha Kanık-Yüksek, Sara Espinosa-Padilla, Sathishkumar Ramaswamy, Satoshi Okada, Sefika Elmas Bozdemir, Selma Erol Aytekin, Şemsi Nur Karabela, Sevgi Keles, Sevtap Senoglu, Shen-Ying Zhang, Sotirija Duvlis, Stefan N. Constantinescu, Stephanie Boisson-Dupuis, Stuart E. Turvey, Stuart G. Tangye, Takaki Asano, Tayfun Ozcelik, Tom Le Voyer, Tom Maniatis, Tomohiro Morio, Trine H. Mogensen, Vanessa Sancho-Shimizu, Vivien Beziat, Xavier Solanich, Yenan Bryceson, Yu-Lung Lau & Yuval Itan, SARS-CoV-2 infection is benign in most individuals but, in around 10% of cases, it triggers hypoxaemic COVID-19 pneumonia, which leads to critical illness in around 3% of cases. The ensuing risk of death (approximately 1% across age and gender) doubles every five years from childhood onwards and is around 1.5 times greater in men than in women. Here we review the molecular and cellular determinants of critical COVID-19 pneumonia. Inborn errors of type I interferons (IFNs), including autosomal TLR3 and X-chromosome-linked TLR7 deficiencies, are found in around 1–5% of patients with critical pneumonia under 60 years old, and a lower proportion in older patients. Pre-existing auto-antibodies neutralizing IFNα, IFNβ and/or IFNω, which are more common in men than in women, are found in approximately 15–20% of patients with critical pneumonia over 70 years old, and a lower proportion in younger patients. Thus, at least 15% of cases of critical COVID-19 pneumonia can be explained. The TLR3- and TLR7-dependent production of type I IFNs by respiratory epithelial cells and plasmacytoid dendritic cells, respectively, is essential for host defence against SARS-CoV-2. In ways that can depend on age and sex, insufficient type I IFN immunity in the respiratory tract during the first few days of infection may account for the spread of the virus, leading to pulmonary and systemic inflammation., The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St Giles Foundation, the National Institutes of Health (NIH) (R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences (NCATS), the NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, the Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the Yale High Performance Computing Center (S10OD018521), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the ‘Investments for the Future’ program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project (ANR-20-COVI-0003), ANRS Nord-Sud (ANRS-COV05), ANR grant GENVIR (ANR-20-CE93-003), ANR AABIFNCOV (ANR-20-CO11-0001) and ANR MIS-C (ANR 21-COVR-0039, GenMIS-C) projects, the European Union’s Horizon 2020 research and innovation program under grant agreement no. 824110 (EASI-Genomics), the Square Foundation, Grandir—Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, Fondation du Souffle, The French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the University of Paris. P.B. was supported by the FRM (EA20170638020) and the MD-PhD programme of the Imagine Institute (with the support of the Fondation Bettencourt Schueller). G.N. is supported by Regione Lazio (Research Group Projects 2020) no. A0375-2020-36663, GecoBiomark. H.C.S. and L.D.N. are supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
Published: 2022

30. From your nose to your toes: a review of severe acute respiratory syndrome Coronavirus 2 pandemic‒associated pernio

Author: Tayfun Ozcelik, Mohammed Shahrooei, D. Mansouri, Lisa F.P. Ng, Isabelle Meyts, Pere Soler-Palacín, Aurora Pujol, Samira Asgari, Anne Marie Singh, Saleh Al-Muhsen, Jacques Fellay, Graziano Pesole, Giuseppe Novelli, John J. Moon, Kristina Mironska, Jennifer M Tran, Evangelos Andreakos, Anna Shcherbina, Antonio Condino-Neto, Filomeen Haerynck, Yu-Lung Lau, Sara Espinosa-Padilla, Carlos Flores, Jean-Laurent Casanova, Anna M. Planas, Beth A. Drolet, Donald C. Vinh, Jordi Pérez Tur, Biggs Catherine, Diederik van de Beek, Alexandre Bolze, Kai Kisand, Ahmad Abou Tayoun, Timokratis Karamitros, Colobran Roger, Edward W. Cowen, Elena Hsieh, Carlos Rodríguez-Gallego, Alexandre Belot, Alessandro Aiuti, Anastasiia Bondarenko, Laurent Abel, Anna Sediva, Rebeca Perez de Diego, Rabih Halwani, Petter Brodin, Keisuke Okamoto, Giorgio Casari, Cliona O'Farrelly, Jacqueline W. Mays, Ivan Tancevski, Furkan Uddin, Clifton L. Dalgard, Qiang Pan-Hammarström, Carolina Prando, Satoshi Okada, Trine H. Mogensen, Laurent Renia, Lisa M. Arkin, Özçelik, Tayfun, Arkin, L. M., Moon, J. J., Tran, J. M., Asgari, S., O'Farrelly, C., Casanova, J. -L., Cowen, E. W., Mays, J. W., Singh, A. M., Drolet, B. A., Aiuti, A., Belot, A., Bolze, A., Bondarenko, A., Sediva, A., Shcherbina, A., Planas, A. M., Condino-Neto, A., Pujol, A., Catherine, B., Flores, C., Rodriguez-Gallego, C., Prando, C., Dalgard, C. L., Roger, C., Mansouri, D., van de Beek, D., Vinh, D. C., Hsieh, E., Andreakos, E., Haerynck, F., Uddin, F., Casari, G., Novelli, G., Pesole, G., Meyts, I., Tancevski, I., Fellay, J., Tur, J., Kisand, K., Okamoto, K., Mironska, K., Abel, L., Renia, L., Ng, L. F. P., Shahrooei, M., Soler-Palacin, P., Brodin, P., Pan-Hammarstrom, Q., Halwani, R., Perez de Diego, R., Al-Muhsen, S., Espinosa-Padilla, S., Okada, S., Ozcelik, T., Tayoun, A. A., Karamitros, T., Mogensen, T. H., and Lau, Y. -L.
Subjects: Dermatology, Plasmacytoid dendritic cell, Review, Biochemistry, type 1 interferon, (IFN-1), Immune system, Immunity, medicine, Animals, Humans, Seroconversion, Molecular Biology, Nose, Pernio, Innate immune system, I INTERFERON, business.industry, Plasmacytoid Dendritic Cell, (pDC), SARS-CoV-2, fungi, COVID-19, Cell Biology, biochemical phenomena, metabolism, and nutrition, medicine.disease, Pathophysiology, Innate Immunity, Immunity, Innate, Chilblains, Pneumonia, medicine.anatomical_structure, Settore MED/03, INFECTIONS, Immunology, Interferon Type I, Eccrine Gland, business, Severe Acute Respiratory Syndrome Coronavirus 2, (SARS-CoV-2)
Abstract: Despite thousands of reported patients with pandemic-associated pernio, low rates of seroconversion and PCR positivity have defied causative linkage to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pernio in uninfected children is associated with monogenic disorders of excessive IFN-1 immunity, whereas severe COVID-19 pneumonia can result from insufficient IFN-1. Moreover, SARS-CoV-2 spike protein and robust IFN-1 response are seen in the skin of patients with pandemic-associated pernio, suggesting an excessive innate immune skin response to SARS-CoV-2. Understanding the pathophysiology of this phenomenon may elucidate the host mechanisms that drive a resilient immune response to SARS-CoV-2 and could produce relevant therapeutic targets.
Published: 2021

31. ImmunoTyper-SR: A computational approach for genotyping immunoglobulin heavy chain variable genes using short-read data

Author: Michael K.B. Ford, Ananth Hari, Oscar Rodriguez, Junyan Xu, Justin Lack, Cihan Oguz, Yu Zhang, Andrew J. Oler, Ottavia M. Delmonte, Sarah E. Weber, Mary Magliocco, Jason Barnett, Sandhya Xirasagar, Smilee Samuel, Luisa Imberti, Paolo Bonfanti, Andrea Biondi, Clifton L. Dalgard, Stephen Chanock, Lindsey B. Rosen, Steven M. Holland, Helen C. Su, Luigi D. Notarangelo, Uzi Vishkin, Corey T. Watson, S. Cenk Sahinalp, Kerry Dobbs, Elana Shaw, Miranda F. Tompkins, Camille Alba, Adelani Adeleye, Samuel Li, Jingwen Gu, Ford, M, Hari, A, Rodriguez, O, Xu, J, Lack, J, Oguz, C, Zhang, Y, Weber, S, Magliocco, M, Barnett, J, Xirasagar, S, Samuel, S, Imberti, L, Bonfanti, P, Biondi, A, Dalgard, C, Chanock, S, Rosen, L, Holland, S, Su, H, Notarangelo, L, Vishkin, U, Watson, C, and Sahinalp, S
Subjects: genomic, ILP, next generation sequencing, algorithm, computational biology, Histology, genotyping, immunogenomic, Cell Biology, immunoglobulin, optimization, WGS, Pathology and Forensic Medicine
Abstract: Human immunoglobulin heavy chain (IGH) locus on chromosome 14 includes more than 40 functional copies of the variable gene (IGHV), which are critical for the structure of antibodies that identify and neutralize pathogenic invaders as a part of the adaptive immune system. Because of its highly repetitive sequence composition, the IGH locus has been particularly difficult to assemble or genotype when using standard short-read sequencing technologies. Here, we introduce ImmunoTyper-SR, an algorithmic tool for the genotyping and CNV analysis of the germline IGHV genes on Illumina whole-genome sequencing (WGS) data using a combinatorial optimization formulation that resolves ambiguous read mappings. We have validated ImmunoTyper-SR on 12 individuals, whose IGHV allele composition had been independently validated, as well as concordance between WGS replicates from nine individuals. We then applied ImmunoTyper-SR on 585 COVID patients to investigate the associations between IGHV alleles and anti-type I IFN autoantibodies, which were previously associated with COVID-19 severity.
Published: 2022

32. A Global Effort to Define the Human Genetics of Protective Immunity to SARS-CoV-2 Infection

Author: Jean-Laurent Casanova, Helen C. Su, Laurent Abel, Alessandro Aiuti, Saleh Almuhsen, Andres Augusto Arias, Paul Bastard, Catherine Biggs, Dusan Bogunovic, Bertrand Boisson, Stephanie Boisson-Dupuis, Alexandre Bolze, Anastasia Bondarenko, Aziz Bousfiha, Petter Brodin, Jacinta Bustamante, Manish Butte, Giorgio Casari, Michael Ciancanelli, Aurelie Cobat, Antonio Condino-Neto, Megan Cooper, Clifton Dalgard, Sara Espinosa, Hagit Feldman, Jacques Fellay, Jose Luis Franco, David Hagin, Yuval Itan, Emmanuelle Jouanguy, Carrie Lucas, Davood Mansouri, Isabelle Meyts, Joshua Milner, Trine Mogensen, Tomohiro Morio, Lisa Ng, Luigi D. Notarangelo, Satoshi Okada, Tayfun Ozcelik, Pere Soler Palacín, Anna Planas, Carolina Prando, Anne Puel, Aurora Pujol, Claire Redin, Laurent Renia, Jose Carlos Rodriguez Gallego, Lluis Quintana-Murci, Vanessa Sancho-Shimizu, Vijay Sankaran, Mikko R.J. Seppänen, Mohammad Shahrooei, Andrew Snow, András Spaan, Stuart Tangye, Jordi Perez Tur, Stuart Turvey, Donald C. Vinh, Horst von Bernuth, Xiaochuan Wang, Pawel Zawadzki, Qian Zhang, Shenying Zhang, Casanova, J. -L., Su, H. C., Abel, L., Aiuti, A., Almuhsen, S., Arias, A. A., Bastard, P., Biggs, C., Bogunovic, D., Boisson, B., Boisson-Dupuis, S., Bolze, A., Bondarenko, A., Bousfiha, A., Brodin, P., Bustamante, J., Butte, M., Casari, G., Ciancanelli, M., Cobat, A., Condino-Neto, A., Cooper, M., Dalgard, C., Espinosa, S., Feldman, H., Fellay, J., Franco, J. L., Hagin, D., Itan, Y., Jouanguy, E., Lucas, C., Mansouri, D., Meyts, I., Milner, J., Mogensen, T., Morio, T., Ng, L., Notarangelo, L. D., Okada, S., Ozcelik, T., Palacin, P. S., Planas, A., Prando, C., Puel, A., Pujol, A., Redin, C., Renia, L., Rodriguez Gallego, J. C., Quintana-Murci, L., Sancho-Shimizu, V., Sankaran, V., Seppanen, M. R. J., Shahrooei, M., Snow, A., Spaan, A., Tangye, S., Tur, J. P., Turvey, S., Vinh, D. C., von Bernuth, H., Wang, X., Zawadzki, P., Zhang, Q., Zhang, S., UKRI Future Leader's Fellowship, and Özçelik, Tayfun
Subjects: Pneumonia, Viral, Disease, Biology, Infections, Virus, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Betacoronavirus, 0302 clinical medicine, Pandemic, Genetic variation, medicine, Humans, Genetic Predisposition to Disease, COVID Human Genetic Effort, Pandemics, 11 Medical and Health Sciences, Genetic Association Studies, 030304 developmental biology, Disease Resistance, 0303 health sciences, Viral Epidemiology, Genome, Human, SARS-CoV-2, Age Factors, Genetic Diseases, Inborn, COVID-19, Genetic Variation, 06 Biological Sciences, biology.organism_classification, medicine.disease, Human genetics, Immunology, Host-Pathogen Interactions, Coronavirus Infections, Pneumonia (non-human), 030217 neurology & neurosurgery, Developmental Biology
Abstract: SARS-CoV-2 infection displays immense inter-individual clinical variability, ranging from silent infection to lethal disease. The role of human genetics in determining clinical response to the virus remains unclear. Studies of outliers—individuals remaining uninfected despite viral exposure and healthy young patients with life-threatening disease—present a unique opportunity to reveal human genetic determinants of infection and disease.
Published: 2020

33. 4.P.150 Four days weighed food record as routine procedure to patients with coronary heart disease in dietary intervention programmes

Author: Dalgård, C., Thurøe, A., Haastrup, B., Haghfelt, T., and Stender, S.
Published: 1997
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34. Intermediate HTT CAG repeats worsen disease severity in amyotrophic lateral sclerosis.

Author: Grassano M, Canosa A, D'Alfonso S, Corrado L, Brodini G, Koumantakis E, Cugnasco P, Manera U, Vasta R, Palumbo F, Mazzini L, Gallone S, Moglia C, Dewan R, Chia R, Ding J, Dalgard C, Gibbs RJ, Scholz S, Calvo A, Traynor B, and Chio A
Abstract: Competing Interests: Competing interests: AChio serves on scientific advisory boards for Mitsubishi Tanabe, Roche, Biogen, Denali Pharma, AC Immune, Biogen, Lilly, and Cytokinetics and has received a research grant from Biogen. BT holds the US, Canadian and European patents on the clinical testing and therapeutic intervention for the hexanucleotide repeat expansion in C9orf72. BT and SS received research support from Cerevel Therapeutics. ACalvo has received a research grant from Cytokinetics. MG has received grants from the American Academy of Neurology, the American Brain Foundation and the ALS Association.
Published: 2024
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35. Missense and loss-of-function variants at GWAS loci in familial Alzheimer's disease.

Author: Gunasekaran TI, Reyes-Dumeyer D, Faber KM, Goate A, Boeve B, Cruchaga C, Pericak-Vance M, Haines JL, Rosenberg R, Tsuang D, Mejia DR, Medrano M, Lantigua RA, Sweet RA, Bennett DA, Wilson RS, Alba C, Dalgard C, Foroud T, Vardarajan BN, and Mayeux R
Abstract: Background: Few rare variants have been identified in genetic loci from genome-wide association studies (GWAS) of Alzheimer's disease (AD), limiting understanding of mechanisms, risk assessment, and genetic counseling., Methods: Using genome sequencing data from 197 families in the National Institute on Aging Alzheimer's Disease Family Based Study and 214 Caribbean Hispanic families, we searched for rare coding variants within known GWAS loci from the largest published study., Results: Eighty-six rare missense or loss-of-function (LoF) variants completely segregated in 17.5% of families, but in 91 (22.1%) families Apolipoprotein E (APOE)-𝜀4 was the only variant segregating. However, in 60.3% of families, APOE 𝜀4, missense, and LoF variants were not found within the GWAS loci., Discussion: Although APOE 𝜀4and several rare variants were found to segregate in both family datasets, many families had no variant accounting for their disease. This suggests that familial AD may be the result of unidentified rare variants., Highlights: Rare coding variants from GWAS loci segregate in familial Alzheimer's disease. Missense or loss of function variants were found segregating in nearly 7% of families. APOE-𝜀4 was the only segregating variant in 29.7% in familial Alzheimer's disease. In Hispanic and non-Hispanic families, different variants were found in segregating genes. No coding variants were found segregating in many Hispanic and non-Hispanic families., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
Published: 2024
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36. Whole-genome sequencing analysis reveals new susceptibility loci and structural variants associated with progressive supranuclear palsy.

Author: Wang H, Chang TS, Dombroski BA, Cheng PL, Patil V, Valiente-Banuet L, Farrell K, Mclean C, Molina-Porcel L, Rajput A, De Deyn PP, Le Bastard N, Gearing M, Kaat LD, Van Swieten JC, Dopper E, Ghetti BF, Newell KL, Troakes C, de Yébenes JG, Rábano-Gutierrez A, Meller T, Oertel WH, Respondek G, Stamelou M, Arzberger T, Roeber S, Müller U, Hopfner F, Pastor P, Brice A, Durr A, Le Ber I, Beach TG, Serrano GE, Hazrati LN, Litvan I, Rademakers R, Ross OA, Galasko D, Boxer AL, Miller BL, Seeley WW, Van Deerlin VM, Lee EB, White CL 3rd, Morris H, de Silva R, Crary JF, Goate AM, Friedman JS, Leung YY, Coppola G, Naj AC, Wang LS, Dalgard C, Dickson DW, Höglinger GU, Schellenberg GD, Geschwind DH, and Lee WP
Subjects: Humans, Male, Female, Aged, Middle Aged, Aged, 80 and over, Supranuclear Palsy, Progressive genetics, Genetic Predisposition to Disease genetics, Whole Genome Sequencing, Genome-Wide Association Study, Polymorphism, Single Nucleotide genetics
Abstract: Background: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease characterized by the accumulation of aggregated tau proteins in astrocytes, neurons, and oligodendrocytes. Previous genome-wide association studies for PSP were based on genotype array, therefore, were inadequate for the analysis of rare variants as well as larger mutations, such as small insertions/deletions (indels) and structural variants (SVs)., Method: In this study, we performed whole genome sequencing (WGS) and conducted association analysis for single nucleotide variants (SNVs), indels, and SVs, in a cohort of 1,718 cases and 2,944 controls of European ancestry. Of the 1,718 PSP individuals, 1,441 were autopsy-confirmed and 277 were clinically diagnosed., Results: Our analysis of common SNVs and indels confirmed known genetic loci at MAPT, MOBP, STX6, SLCO1A2, DUSP10, and SP1, and further uncovered novel signals in APOE, FCHO1/MAP1S, KIF13A, TRIM24, TNXB, and ELOVL1. Notably, in contrast to Alzheimer's disease (AD), we observed the APOE ε2 allele to be the risk allele in PSP. Analysis of rare SNVs and indels identified significant association in ZNF592 and further gene network analysis identified a module of neuronal genes dysregulated in PSP. Moreover, seven common SVs associated with PSP were observed in the H1/H2 haplotype region (17q21.31) and other loci, including IGH, PCMT1, CYP2A13, and SMCP. In the H1/H2 haplotype region, there is a burden of rare deletions and duplications (P = 6.73 × 10 -3 ) in PSP., Conclusions: Through WGS, we significantly enhanced our understanding of the genetic basis of PSP, providing new targets for exploring disease mechanisms and therapeutic interventions., (© 2024. The Author(s).)
Published: 2024
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37. SOS1 inhibition enhances the efficacy of and delays resistance to G12C inhibitors in lung adenocarcinoma.

Author: Daley BR, Sealover NE, Sheffels E, Hughes JM, Gerlach D, Hofmann MH, Kostyrko K, Mair B, Linke A, Beckley Z, Frank A, Dalgard C, and Kortum RL
Abstract: Clinical effectiveness of KRAS G12C inhibitors (G12Cis) is limited both by intrinsic and acquired resistance, necessitating the development of combination approaches. We found that targeting proximal receptor tyrosine kinase (RTK) signaling using the SOS1 inhibitor (SOS1i) BI-3406 both enhanced the potency of and delayed resistance to G12Ci treatment, but the extent of SOS1i effectiveness was modulated by both SOS2 expression and the specific mutational landscape. SOS1i enhanced the efficacy of G12Ci and limited rebound RTK/ERK signaling to overcome intrinsic/adaptive resistance, but this effect was modulated by SOS2 protein levels. Survival of drug-tolerant persister (DTP) cells within the heterogeneous tumor population and/or acquired mutations that reactivate RTK/RAS signaling can lead to outgrowth of tumor initiating cells (TICs) that drive therapeutic resistance. G12Ci drug tolerant persister cells showed a 2-3-fold enrichment of TICs, suggesting that these could be a sanctuary population of G12Ci resistant cells. SOS1i re-sensitized DTPs to G12Ci and inhibited G12C-induced TIC enrichment. Co-mutation of the tumor suppressor KEAP1 limits the clinical effectiveness of G12Cis, and KEAP1 and STK11 deletion increased TIC frequency and accelerated the development of acquired resistance to G12Ci in situ . SOS1i both delayed acquired G12Ci resistance and limited the total number of resistant colonies regardless of KEAP1 and STK11 mutational status. These data suggest that SOS1i could be an effective strategy to both enhance G12Ci efficacy and prevent G12Ci resistance regardless of co-mutations.
Published: 2023
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38. Association of Copresence of Pathogenic Variants Related to Amyotrophic Lateral Sclerosis and Prognosis.

Author: Chiò A, Moglia C, Canosa A, Manera U, Grassano M, Vasta R, Palumbo F, Gallone S, Brunetti M, Barberis M, De Marchi F, Dalgard C, Chia R, Mora G, Iazzolino B, Peotta L, Traynor BJ, Corrado L, D'Alfonso S, Mazzini L, and Calvo A
Subjects: Humans, C9orf72 Protein genetics, Alleles, Phenotype, Prognosis, Amyotrophic Lateral Sclerosis epidemiology
Abstract: Background and Objectives: Despite recent advances, it is not clear whether the various genes/genetic variants related to amyotrophic lateral sclerosis (ALS) interact in modifying patients' phenotype. The aim of this study was to determine whether the copresence of genetic variants related to ALS has interactive effects on the course of the disease., Methods: The study population includes 1,245 patients with ALS identified through the Piemonte Register for ALS between 2007 and 2016 and not carrying superoxide dismutase type 1, TAR DNA binding protein, and fused in sarcoma pathogenic variants. Controls were 766 Italian participants age-matched, sex-matched, and geographically matched to cases. We considered Unc-13 homolog A ( UNC13A ) (rs12608932), calmodulin binding transcription activator 1 ( CAMTA1 ) (rs2412208), solute carrier family 11 member 2 ( SLC11A2 ) (rs407135), and zinc finger protein 512B ( ZNF512B ) (rs2275294) variants, as well as ataxin-2 ( ATXN2 ) polyQ intermediate repeats (≥31) and chromosome 9 open reading frame 72 ( C9orf72 ) GGGGCC intronic expansions (≥30)., Results: The median survival time of the whole cohort was 2.67 years (interquartile range [IQR] 1.67-5.25). In univariate analysis, only C9orf72 (2.51 years, IQR 1.74-3.82; p = 0.016), ATXN2 (1.82 years, IQR 1.08-2.33; p < 0.001), and UNC13A C/C (2.3 years, IQR 1.3-3.9; p < 0.001) significantly reduced survival. In Cox multivariable analysis, CAMTA1 also emerged to be independently related to survival (hazard ratio 1.13, 95% CI 1.001-1.30, p = 0.048). The copresence of 2 detrimental alleles/expansions was correlated with shorter survival. In particular, the median survival of patients with CAMTA1 G/G+G/T and UNC13A C/C alleles was 1.67 years (1.16-3.08) compared with 2.75 years (1.67-5.26) of the patients not carrying these variants ( p < 0.001); the survival of patients with CAMTA1 G/G+G/T alleles and ATXN2 ≥31 intermediate polyQ repeats was 1.75 years (0.84-2.18) ( p < 0.001); the survival of patients with ATXN2 ≥31 polyQ repeats and UNC13A C/C allele was 1.33 years (0.84-1.75) ( p < 0.001); the survival of patients with C9ORF72 ≥30 and UNC13A C/C allele was 1.66 years (1.41-2.16). Each pair of detrimental alleles/expansions was associated to specific clinical phenotypes., Discussion: We showed that gene variants acting as modifiers of ALS survival or phenotype can act on their own or in unison. Overall, 54% of patients carried at least 1 detrimental common variant or repeat expansion, emphasizing the clinical impact of our findings. In addition, the identification of the interactive effects of modifier genes represents a crucial clue for explaining ALS clinical heterogeneity and should be considered when designing and interpreting clinical trials results., (Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)
Published: 2023
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39. Unexpected frequency of the pathogenic AR CAG repeat expansion in the general population.

Author: Zanovello M, Ibáñez K, Brown AL, Sivakumar P, Bombaci A, Santos L, van Vugt JJFA, Narzisi G, Karra R, Scholz SW, Ding J, Gibbs JR, Chiò A, Dalgard C, Weisburd B, Hanna MG, Greensmith L, Phatnani H, Veldink JH, Traynor BJ, Polke J, Houlden H, Fratta P, and Tucci A
Subjects: Humans, Male, Muscular Atrophy, Polymerase Chain Reaction, Trinucleotide Repeat Expansion genetics, Receptors, Androgen genetics, Muscular Atrophy, Spinal genetics
Abstract: CAG repeat expansions in exon 1 of the AR gene on the X chromosome cause spinal and bulbar muscular atrophy, a male-specific progressive neuromuscular disorder associated with a variety of extra-neurological symptoms. The disease has a reported male prevalence of approximately 1:30 000 or less, but the AR repeat expansion frequency is unknown. We established a pipeline, which combines the use of the ExpansionHunter tool and visual validation, to detect AR CAG expansion on whole-genome sequencing data, benchmarked it to fragment PCR sizing, and applied it to 74 277 unrelated individuals from four large cohorts. Our pipeline showed sensitivity of 100% [95% confidence interval (CI) 90.8-100%], specificity of 99% (95% CI 94.2-99.7%), and a positive predictive value of 97.4% (95% CI 84.4-99.6%). We found the mutation frequency to be 1:3182 (95% CI 1:2309-1:4386, n = 117 734) X chromosomes-10 times more frequent than the reported disease prevalence. Modelling using the novel mutation frequency led to estimate disease prevalence of 1:6887 males, more than four times more frequent than the reported disease prevalence. This discrepancy is possibly due to underdiagnosis of this neuromuscular condition, reduced penetrance, and/or pleomorphic clinical manifestations., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)
Published: 2023
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40. Transcriptomic Profiling and Pathway Analysis of Mesenchymal Stem Cells Following Low Dose-Rate Radiation Exposure.

Author: Slaven JE, Wilkerson M, Soltis AR, Rittase WB, Bradfield DT, Bylicky M, Cary L, Tsioplaya A, Bouten R, Dalgard C, and Day RM
Abstract: Low dose-rate radiation exposure can occur in medical imaging, as background from environmental or industrial radiation, and is a hazard of space travel. In contrast with high dose-rate radiation exposure that can induce acute life-threatening syndromes, chronic low-dose radiation is associated with Chronic Radiation Syndrome (CRS), which can alter environmental sensitivity. Secondary effects of chronic low dose-rate radiation exposure include circulatory, digestive, cardiovascular, and neurological diseases, as well as cancer. Here, we investigated 1-2 Gy, 0.66 cGy/h, 60 Co radiation effects on primary human mesenchymal stem cells (hMSC). There was no significant induction of apoptosis or DNA damage, and cells continued to proliferate. Gene ontology (GO) analysis of transcriptome changes revealed alterations in pathways related to cellular metabolism (cholesterol, fatty acid, and glucose metabolism), extracellular matrix modification and cell adhesion/migration, and regulation of vasoconstriction and inflammation. Interestingly, there was increased hypoxia signaling and increased activation of pathways regulated by iron deficiency, but Nrf2 and related genes were reduced. The data were validated in hMSC and human lung microvascular endothelial cells using targeted qPCR and Western blotting. Notably absent in the GO analysis were alteration pathways for DNA damage response, cell cycle inhibition, senescence, and pro-inflammatory response that we previously observed for high dose-rate radiation exposure. Our findings suggest that cellular gene transcription response to low dose-rate ionizing radiation is fundamentally different compared to high-dose-rate exposure. We hypothesize that cellular response to hypoxia and iron deficiency are driving processes, upstream of the other pathway regulation.
Published: 2023
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41. Clinical and Metabolic Signature of UNC13A rs12608932 Variant in Amyotrophic Lateral Sclerosis.

Author: Calvo A, Canosa A, Moglia C, Manera U, Grassano M, Vasta R, Palumbo F, Cugnasco P, Gallone S, Brunetti M, De Marchi F, Arena V, Pagani M, Dalgard C, Scholz SW, Chia R, Corrado L, Dalfonso S, Mazzini L, Traynor BJ, and Chio A
Abstract: Background and Objectives: To characterize the clinical and cognitive behavioral phenotype and brain 18 F-2-fluoro-2-deoxy-d-glucose-PET ( 18 F-FDG-PET) metabolism of patients with amyotrophic lateral sclerosis (ALS) carrying the rs12608932 variant of the UNC13A gene., Methods: The study population included 1,409 patients with ALS without C9orf72, SOD1, TARDBP , and FUS mutations identified through a prospective epidemiologic ALS register. Control participants included 1,012 geographically matched, age-matched, and sex-matched participants. Clinical and cognitive differences between patients carrying the C/C rs12608932 genotype and those carrying the A/A + A/C genotype were assessed. A subset of patients underwent 18 F-FDG-PET., Results: The C/C genotype was associated with an increased risk of ALS (odds ratio: 1.54, 95% confidence interval 1.18-2.01, p = 0.001). Patients with the C/C genotype were older, had more frequent bulbar onset, and manifested a higher rate of weight loss. In addition, they showed significantly reduced performance in the letter fluency test, fluency domain of Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and story-based empathy task (reflecting social cognition). Patients with the C/C genotype had a shorter survival (median survival time, C/C 2.25 years, interquartile range [IQR] 1.33-3.92; A/A + C/C: 2.90 years, IQR 1.74-5.41; p = 0.0001). In Cox multivariable analysis, C/C genotype resulted to be an independent prognostic factor. Finally, patients with a C/C genotype had a specific pattern of hypometabolism on brain 18 F-FDG-PET extending to frontal and precentral areas of the right hemisphere., Discussion: C/C rs12608932 genotype of UNC13A is associated with a specific motor and cognitive/behavioral phenotype, which reflects on 18 F-FDG-PET findings. Our observations highlight the importance of adding the rs12608932 variant in UNC13A to the ALS genetic panel to refine the individual prognostic prediction and reduce heterogeneity in clinical trials., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
Published: 2022
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42. ATXN2 intermediate expansions in amyotrophic lateral sclerosis.

Author: Glass JD, Dewan R, Ding J, Gibbs JR, Dalgard C, Keagle PJ, Shankaracharya, García-Redondo A, Traynor BJ, Chia R, and Landers JE
Subjects: Ataxin-2, Humans, Phenotype, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Lewy Body Disease
Abstract: Intermediate CAG (polyQ) expansions in the gene ataxin-2 (ATXN2) are now recognized as a risk factor for amyotrophic lateral sclerosis. The threshold for increased risk is not yet firmly established, with reports ranging from 27 to 31 repeats. We investigated the presence of ATXN2 polyQ expansions in 9268 DNA samples collected from people with amyotrophic lateral sclerosis, amyotrophic lateral sclerosis with frontotemporal dementia, frontotemporal dementia alone, Lewy body dementia and age matched controls. This analysis confirmed ATXN2 intermediate polyQ expansions of ≥31 as a risk factor for amyotrophic lateral sclerosis with an odds ratio of 6.31. Expansions were an even greater risk for amyotrophic lateral sclerosis with frontotemporal dementia (odds ratio 27.59) and a somewhat lesser risk for frontotemporal dementia alone (odds ratio 3.14). There was no increased risk for Lewy body dementia. In a subset of 1362 patients with amyotrophic lateral sclerosis with complete clinical data, we could not confirm previous reports of earlier onset of amyotrophic lateral sclerosis or shorter survival in 25 patients with expansions. These new data confirm ≥31 polyQ repeats in ATXN2 increase the risk for amyotrophic lateral sclerosis, and also for the first time show an even greater risk for amyotrophic lateral sclerosis with frontotemporal dementia. The lack of a more aggressive phenotype in amyotrophic lateral sclerosis patients with expansions has implications for ongoing gene-silencing trials for amyotrophic lateral sclerosis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Published: 2022
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43. Exploring the phenotype of Italian patients with ALS with intermediate ATXN2 polyQ repeats.

Author: Chio A, Moglia C, Canosa A, Manera U, Grassano M, Vasta R, Palumbo F, Gallone S, Brunetti M, Barberis M, De Marchi F, Dalgard C, Chia R, Mora G, Iazzolino B, Peotta L, Traynor B, Corrado L, D'Alfonso S, Mazzini L, and Calvo A
Abstract: Objective: To detect the clinical characteristics of patients with amyotrophic lateral sclerosis (ALS) carrying an intermediate ATXN2 polyQ number of repeats in a large population-based series of Italian patients with ALS., Methods: The study population includes 1330 patients with ALS identified through the Piemonte and Valle d'Aosta Register for ALS, diagnosed between 2007 and 2019 and not carrying C9orf72, SOD1, TARDBP and FUS mutations. Controls were 1274 age, sex and geographically matched Italian subjects, identified through patients' general practitioners., Results: We found 42 cases and 4 controls with≥31 polyQ repeats, corresponding to an estimated OR of 10.4 (95% CI 3.3 to 29.0). Patients with≥31 polyQ repeats (ATXN2+) compared with those without repeat expansion (ATXN2-) had more frequently a spinal onset (p=0.05), a shorter diagnostic delay (p=0.004), a faster rate of ALSFRS-R progression (p=0.004) and King's progression (p=0.004), and comorbid frontotemporal dementia (7 (28.0%) vs 121 (13.4%), p=0.037). ATXN2+ patients had a 1-year shorter survival (ATXN2+ patients 1.82 years, 95% CI 1.08 to 2.51; ATXN2- 2.84 years, 95% CI 1.67 to 5.58, p=0.0001). ATXN2 polyQ intermediate repeats was independently related to a worse outcome in Cox multivariable analysis (p=0.006)., Conclusions: In our population-based cohort, ATXN2+ patients with ALS have a distinctive phenotype, characterised by a more rapid disease course and a shorter survival. In addition, ATXN2+ patients have a more severe impairment of cognitive functions. These findings have relevant implications on clinical practice, including the possibility of refining the individual prognostic prediction and improving the design of ALS clinical trials, in particular as regards as those targeted explicitly to ATXN2 ., Competing Interests: Competing interests: Adriano Chiò serves on scientific advisory boards for Mitsubishi Tanabe, Biogen, Roche, Denali Pharma, Cytokinetics, Lilly, and Amylyx Pharmaceuticals and has received a research grant from Biogen. Cristina Moglia, Antonio Canosa, Umberto Manera, Maurizio Grassano, Rosario Vasta, Francesca Palumbo, Salvatore Gallone, Maura Brunetti, Fabiola De Marchi, Clifton L. Dalgard, Ruth Chia, Gabriele Mora, Lucia Corrado, Sandra D’Alfonso, Letizia Mazzini no disclosures. Dr Traynor holds the US, Canadian, and European patents on the clinical testing and therapeutic intervention for the hexanucleotide repeat expansion in C9orf72. Andrea Calvo has received a research grant from Cytokinetics., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)
Published: 2022
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44. Systematic evaluation of genetic mutations in ALS: a population-based study.

Author: Grassano M, Calvo A, Moglia C, Sbaiz L, Brunetti M, Barberis M, Casale F, Manera U, Vasta R, Canosa A, D'Alfonso S, Corrado L, Mazzini L, Dalgard C, Karra R, Chia R, Traynor B, and Chiò A
Abstract: Background: A genetic diagnosis in Amyotrophic Lateral Sclerosis (ALS) can inform genetic counselling, prognosis and, in the light of incoming gene-targeted therapy, management. However, conventional genetic testing strategies are often costly and time-consuming., Objective: To evaluate the diagnostic yield and advantages of whole-genome sequencing (WGS) as a standard diagnostic genetic test for ALS., Methods: In this population-based cohort study, 1043 ALS patients from the Piemonte and Valle d'Aosta Register for ALS and 755 healthy individuals were screened by WGS for variants in 42 ALS-related genes and for repeated-expansions in C9orf72 and ATXN2., Results: A total of 279 ALS cases (26.9%) received a genetic diagnosis, namely 75.2% of patients with a family history of ALS and 21.5% of sporadic cases. The mutation rate among early-onset ALS patients was 43.9%, compared with 19.7% of late-onset patients. An additional 14.6% of the cohort carried a genetic factor that worsen prognosis., Conclusions: Our results suggest that, because of its high diagnostic yield and increasingly competitive costs, along with the possibility of retrospectively reassessing newly described genes, WGS should be considered as standard genetic testing for all ALS patients. Additionally, our results provide a detailed picture of the genetic basis of ALS in the general population., Competing Interests: Competing interests: MG, CM, LS, MBr, MBa, FC, UM, RV, AC, SD'A, LC, LM, CD, RK and RC report no disclosures. AC has received research grant from Cytokinetics. BT holds European, Canadian and American patents on the clinical testing and therapeutic intervention for the hexanucleotide repeat expansion of C9orf72. AC serves on scientific advisory boards for Mitsubishi Tanabe, Roche and Cytokinetics, and has received a research grant from Italfarmaco., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)
Published: 2022
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45. Germline mutation landscape of DNA damage repair genes in African Americans with prostate cancer highlights potentially targetable RAD genes.

Author: Kohaar I, Zhang X, Tan SH, Nousome D, Babcock K, Ravindranath L, Sukumar G, Mcgrath-Martinez E, Rosenberger J, Alba C, Ali A, Young D, Chen Y, Cullen J, Rosner IL, Sesterhenn IA, Dobi A, Chesnut G, Turner C, Dalgard C, Wilkerson MD, Pollard HB, Srivastava S, and Petrovics G
Subjects: DNA Damage genetics, Germ-Line Mutation, Humans, Male, Mutation, Black or African American genetics, Prostatic Neoplasms genetics, Prostatic Neoplasms pathology
Abstract: In prostate cancer, emerging data highlight the role of DNA damage repair genes (DDRGs) in aggressive forms of the disease. However, DDRG mutations in African American men are not yet fully defined. Here, we profile germline mutations in all known DDRGs (N = 276) using whole genome sequences from blood DNA of a matched cohort of patients with primary prostate cancer comprising of 300 African American and 300 European Ancestry prostate cancer patients, to determine whether the mutation status can enhance patient stratification for specific targeted therapies. Here, we show that only 13 of the 46 DDRGs identified with pathogenic/likely pathogenic mutations are present in both African American and European ancestry patients. Importantly, RAD family genes (RAD51, RAD54L, RAD54B), which are potentially targetable, as well as PMS2 and BRCA1, are among the most frequently mutated DDRGs in African American, but not in European Ancestry patients., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Published: 2022
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46. Genetic regulation of OAS1 nonsense-mediated decay underlies association with risk of severe COVID-19.

Author: Banday AR, Stanifer ML, Florez-Vargas O, Onabajo OO, Zahoor MA, Papenberg BW, Ring TJ, Lee CH, Andreakos E, Arons E, Barsh G, Biesecker LG, Boyle DL, Burnett-Hartman A, Carrington M, Chang E, Choe PG, Chrisholm RL, Dalgard C, Edberg J, Erdmann N, Feigelson HS, Firestein GS, Gehring AJ, Ho M, Holland S, Hutchinson AA, Im H, Ison MG, Kim HB, Kreitman RJ, Korf BR, Mirabello L, Pacheco JA, Peluso MJ, Rader DJ, Redden DT, Ritchie MD, Rosenbloom B, Sant Anna HP, Savage S, Siouti E, Triantafyllia V, Vargas JM, Verma A, Vij V, Wesemann DR, Yeager M, Yu X, Zhang Y, Boulant S, Chanock SJ, Feld JJ, and Prokunina-Olsson L
Abstract: Genomic regions have been associated with COVID-19 susceptibility and outcomes, including the chr12q24.13 locus encoding antiviral proteins OAS1-3. Here, we report genetic, functional, and clinical insights into genetic associations within this locus. In Europeans, the risk of hospitalized vs. non-hospitalized COVID-19 was associated with a single 19Kb-haplotype comprised of 76 OAS1 variants included in a 95% credible set within a large genomic fragment introgressed from Neandertals. The risk haplotype was also associated with impaired spontaneous but not treatment-induced SARS-CoV-2 clearance in a clinical trial with pegIFN-λ1. We demonstrate that two exonic variants, rs10774671 and rs1131454, affect splicing and nonsense-mediated decay of OAS1 . We suggest that genetically-regulated loss of OAS1 expression contributes to impaired spontaneous clearance of SARS-CoV-2 and elevated risk of hospitalization for COVID-19. Our results provide the rationale for further clinical studies using interferons to compensate for impaired spontaneous SARS-CoV-2 clearance, particularly in carriers of the OAS1 risk haplotypes.
Published: 2021
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47. Proteogenomic landscape of uterine leiomyomas from hereditary leiomyomatosis and renal cell cancer patients.

Author: Bateman NW, Tarney CM, Abulez T, Soltis AR, Zhou M, Conrads K, Litzi T, Oliver J, Hood B, Driggers P, Viollet C, Dalgard C, Wilkerson M, Catherino W, Hamilton CA, Darcy KM, Casablanca Y, Al-Hendy A, Segars J, Conrads TP, and Larry Maxwell G
Subjects: Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Case-Control Studies, Female, Humans, Leiomyomatosis metabolism, Neoplastic Syndromes, Hereditary metabolism, Proteome analysis, Skin Neoplasms metabolism, Uterine Neoplasms metabolism, Biomarkers, Tumor analysis, Fumarate Hydratase genetics, Genetic Predisposition to Disease, Leiomyomatosis pathology, Mutation, Neoplastic Syndromes, Hereditary pathology, Proteogenomics methods, Proteome metabolism, Skin Neoplasms pathology, Uterine Neoplasms pathology
Abstract: Pathogenic mutations in fumarate hydratase (FH) drive hereditary leiomyomatosis and renal cell cancer (HLRCC) and increase the risk of developing uterine leiomyomas (ULMs). An integrated proteogenomic analysis of ULMs from HLRCC (n = 16; FH-mutation confirmed) and non-syndromic (NS) patients (n = 12) identified a significantly higher protein:transcript correlation in HLRCC (R = 0.35) vs. NS ULMs (R = 0.242, MWU p = 0.0015). Co-altered proteins and transcripts (228) included antioxidant response element (ARE) target genes, such as thioredoxin reductase 1 (TXNRD1), and correlated with activation of NRF2-mediated oxidative stress response signaling in HLRCC ULMs. We confirm 185 transcripts previously described as altered between HLRCC and NS ULMs, 51 co-altered at the protein level and several elevated in HLRCC ULMs are involved in regulating cellular metabolism and glycolysis signaling. Furthermore, 367 S-(2-succino)cysteine peptides were identified in HLRCC ULMs, of which sixty were significantly elevated in HLRCC vs. NS ULMs (LogFC = 1.86, MWU p < 0.0001). These results confirm and define novel proteogenomic alterations in uterine leiomyoma tissues collected from HLRCC patients and underscore conserved molecular alterations correlating with inactivation of the FH tumor suppressor gene.
Published: 2021
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48. Distinguishing Smoking-Related Lung Disease Phenotypes Via Imaging and Molecular Features.

Author: Billatos E, Ash SY, Duan F, Xu K, Romanoff J, Marques H, Moses E, Han MK, Regan EA, Bowler RP, Mason SE, Doyle TJ, San José Estépar R, Rosas IO, Ross JC, Xiao X, Liu H, Liu G, Sukumar G, Wilkerson M, Dalgard C, Stevenson C, Whitney D, Aberle D, Spira A, San José Estépar R, Lenburg ME, and Washko GR
Subjects: Academic Medical Centers, Aged, Female, Hospitals, Veterans, Humans, Longitudinal Studies, Male, Middle Aged, Phenotype, Pulmonary Disease, Chronic Obstructive epidemiology, Pulmonary Disease, Chronic Obstructive genetics, United States epidemiology, Pulmonary Disease, Chronic Obstructive chemically induced, Pulmonary Disease, Chronic Obstructive diagnostic imaging, Smoking adverse effects, Tomography, X-Ray Computed
Abstract: Background: Chronic tobacco smoke exposure results in a broad range of lung pathologies including emphysema, airway disease and parenchymal fibrosis as well as a multitude of extra-pulmonary comorbidities. Prior work using CT imaging has identified several clinically relevant subgroups of smoking related lung disease, but these investigations have generally lacked organ specific molecular correlates., Research Question: Can CT imaging be used to identify clinical phenotypes of smoking related lung disease that have specific bronchial epithelial gene expression patterns to better understand disease pathogenesis?, Study Design and Methods: Using K-means clustering, we clustered participants from the COPDGene study (n = 5,273) based on CT imaging characteristics and then evaluated their clinical phenotypes. These clusters were replicated in the Detection of Early Lung Cancer Among Military Personnel (DECAMP) cohort (n = 360), and were further characterized using bronchial epithelial gene expression., Results: Three clusters (preserved, interstitial predominant and emphysema predominant) were identified. Compared to the preserved cluster, the interstitial and emphysema clusters had worse lung function, exercise capacity and quality of life. In longitudinal follow-up, individuals from the emphysema group had greater declines in exercise capacity and lung function, more emphysema, more exacerbations, and higher mortality. Similarly, genes involved in inflammatory pathways (tumor necrosis factor-α, interferon-β) are more highly expressed in bronchial epithelial cells from individuals in the emphysema cluster, while genes associated with T-cell related biology are decreased in these samples. Samples from individuals in the interstitial cluster generally had intermediate levels of expression of these genes., Interpretation: Using quantitative CT imaging, we identified three groups of individuals in older ever-smokers that replicate in two cohorts. Airway gene expression differences between the three groups suggests increased levels of inflammation in the most severe clinical phenotype, possibly mediated by the tumor necrosis factor-α and interferon-β pathways., Clinical Trial Registration: COPDGene (NCT00608764), DECAMP-1 (NCT01785342), DECAMP-2 (NCT02504697)., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Published: 2021
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49. Mutational Analysis of Known ALS Genes in an Italian Population-Based Cohort.

Author: Grassano M, Calvo A, Moglia C, Brunetti M, Barberis M, Sbaiz L, Canosa A, Manera U, Vasta R, Corrado L, D'Alfonso S, Mazzini L, Scholz SW, Dalgard C, Ding J, Gibbs RJ, Chia R, Traynor BJ, and Chiò A
Subjects: Adult, Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis diagnosis, C9orf72 Protein genetics, Case-Control Studies, Cohort Studies, Female, Humans, Italy epidemiology, Male, Middle Aged, Young Adult, Amyotrophic Lateral Sclerosis epidemiology, Amyotrophic Lateral Sclerosis genetics, DNA Mutational Analysis methods, Genetic Predisposition to Disease epidemiology, Genetic Predisposition to Disease genetics, Population Surveillance
Abstract: Objective: To assess the burden of rare genetic variants and to estimate the contribution of known amyotrophic lateral sclerosis (ALS) genes in an Italian population-based cohort, we performed whole genome sequencing in 959 patients with ALS and 677 matched healthy controls., Methods: We performed genome sequencing in a population-based cohort (Piemonte and Valle d'Aosta Registry for ALS [PARALS]). A panel of 40 ALS genes was analyzed to identify potential disease-causing genetic variants and to evaluate the gene-wide burden of rare variants among our population., Results: A total of 959 patients with ALS were compared with 677 healthy controls from the same geographical area. Gene-wide association tests demonstrated a strong association with SOD1 , whose rare variants are the second most common cause of disease after C9orf72 expansion. A lower signal was observed for TARDBP , proving that its effect on our cohort is driven by a few known causal variants. We detected rare variants in other known ALS genes that did not surpass statistical significance in gene-wise tests, thus highlighting that their contribution to disease risk in our cohort is limited., Conclusions: We identified potential disease-causing variants in 11.9% of our patients. We identified the genes most frequently involved in our cohort and confirmed the contribution of rare variants in disease risk. Our results provide further insight into the pathologic mechanism of the disease and demonstrate the importance of genome-wide sequencing as a diagnostic tool., (© 2020 American Academy of Neurology.)
Published: 2021
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50. Magnitude and Dynamics of the T-Cell Response to SARS-CoV-2 Infection at Both Individual and Population Levels.

Author: Snyder TM, Gittelman RM, Klinger M, May DH, Osborne EJ, Taniguchi R, Zahid HJ, Kaplan IM, Dines JN, Noakes MT, Pandya R, Chen X, Elasady S, Svejnoha E, Ebert P, Pesesky MW, De Almeida P, O'Donnell H, DeGottardi Q, Keitany G, Lu J, Vong A, Elyanow R, Fields P, Greissl J, Baldo L, Semprini S, Cerchione C, Nicolini F, Mazza M, Delmonte OM, Dobbs K, Laguna-Goya R, Carreño-Tarragona G, Barrio S, Imberti L, Sottini A, Quiros-Roldan E, Rossi C, Biondi A, Bettini LR, D'Angio M, Bonfanti P, Tompkins MF, Alba C, Dalgard C, Sambri V, Martinelli G, Goldman JD, Heath JR, Su HC, Notarangelo LD, Paz-Artal E, Martinez-Lopez J, Carlson JM, and Robins HS
Abstract: T cells are involved in the early identification and clearance of viral infections and also support the development of antibodies by B cells. This central role for T cells makes them a desirable target for assessing the immune response to SARS-CoV-2 infection. Here, we combined two high-throughput immune profiling methods to create a quantitative picture of the T-cell response to SARS-CoV-2. First, at the individual level, we deeply characterized 3 acutely infected and 58 recovered COVID-19 subjects by experimentally mapping their CD8 T-cell response through antigen stimulation to 545 Human Leukocyte Antigen (HLA) class I presented viral peptides (class II data in a forthcoming study). Then, at the population level, we performed T-cell repertoire sequencing on 1,815 samples (from 1,521 COVID-19 subjects) as well as 3,500 controls to identify shared "public" T-cell receptors (TCRs) associated with SARS-CoV-2 infection from both CD8 and CD4 T cells. Collectively, our data reveal that CD8 T-cell responses are often driven by a few immunodominant, HLA-restricted epitopes. As expected, the T-cell response to SARS-CoV-2 peaks about one to two weeks after infection and is detectable for at least several months after recovery. As an application of these data, we trained a classifier to diagnose SARS-CoV-2 infection based solely on TCR sequencing from blood samples, and observed, at 99.8% specificity, high early sensitivity soon after diagnosis (Day 3-7 = 85.1% [95% CI = 79.9-89.7]; Day 8-14 = 94.8% [90.7-98.4]) as well as lasting sensitivity after recovery (Day 29+/convalescent = 95.4% [92.1-98.3]). These results demonstrate an approach to reliably assess the adaptive immune response both soon after viral antigenic exposure (before antibodies are typically detectable) as well as at later time points. This blood-based molecular approach to characterizing the cellular immune response has applications in clinical diagnostics as well as in vaccine development and monitoring.
Published: 2020
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