11 research outputs found
In-Depth Longitudinal Comparison of Clinical Specimens to Detect SARS-CoV-2.
No full textpeer reviewedThe testing and isolation of patients with coronavirus disease 2019 (COVID-19) are indispensable tools to control the ongoing COVID-19 pandemic. PCR tests are considered the "gold standard" of COVID-19 testing and mostly involve testing nasopharyngeal swab specimens. Our study aimed to compare the sensitivity of tests for various sample specimens. Seventy-five participants with confirmed COVID-19 were included in the study. Nasopharyngeal swabs, oropharyngeal swabs, Oracol-collected saliva, throat washes and rectal specimens were collected along with pooled swabs. Participants were asked to complete a questionnaire to correlate specific clinical symptoms and the symptom duration with the sensitivity of detecting COVID-19 in various sample specimens. Sampling was repeated after 7 to 10 days (T2), then after 14 to 20 days (T3) to perform a longitudinal analysis of sample specimen sensitivity. At the first time point, the highest percentages of SARS-CoV-2-positive samples were observed for nasopharyngeal samples (84.3%), while 74%, 68.2%, 58.8% and 3.5% of throat washing, Oracol-collected saliva, oropharyngeal and rectal samples tested positive, respectively. The sensitivity of all sampling methods except throat wash samples decreased rapidly at later time points compared to the first collection. The throat washing method exhibited better performance than the gold standard nasopharyngeal swab at the second and third time points after the first positive test date. Nasopharyngeal swabs were the most sensitive specimens for early detection after symptom onset. Throat washing is a sensitive alternative method. It was found that SARS-CoV-2 persists longer in the throat and saliva than in the nasopharynx
Transmission of SARS-CoV-2 After COVID-19 Screening and Mitigation Measures for Primary School Children Attending School in Liège, Belgium.
No full textpeer reviewedIMPORTANCE: Recent data suggest a relatively low incidence of COVID-19 among children. The possible role that children attending primary school may play in the transmission of SARS-CoV-2 remains poorly understood. OBJECTIVE: To gain a better understanding of the possible role of children in the transmission of SARS-CoV-2. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was conducted from September 21 to December 31, 2020, in a primary school in Liège, Belgium, among a volunteer sample of 181 children, parents, and school employees. EXPOSURES: Participants were tested for SARS-CoV-2 infection once a week for 15 weeks through throat washing, performed with 5 mL of saline and collected in a sterile tube after approximately 30 seconds of gargling. Quantitative reverse transcription-polymerase chain reaction was performed to detect SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES: In case of test positivity, participants were asked to complete a questionnaire aimed at determining the timing of symptom onset and symptom duration. SARS-CoV-2 genetic sequencing was also performed. Confirmed cases were linked based on available information on known contacts and viral sequences. RESULTS: A total of 181 individuals participated in this study, including 63 children (34 girls [54.0%]; mean [SD] age, 8.6 [1.9] years [range, 5-13 years]) and 118 adults (75 women [63.6%]; mean [SD] age, 42.5 [5.7] years [range, 30-59 years]). Forty-five individuals (24.9%) tested positive: 13 children (20.6%; 95% CI, 10.6%-30.6%) and 32 adults (27.1%; 95% CI, 19.1%-35.7%) (P = .34). Children were more often asymptomatic compared with adults (6 [46.2%; 95% CI, 19.1%-73.3%] vs 4 of 31 [12.9%; 95% CI, 1.3%-24.5%]; P = .04). The median duration of symptoms was shorter in children than in adults (0.00 days [IQR, 0.00-1.00 days] vs 15.00 days [IQR, 7.00-22.00 days]). A reconstruction of the outbreak revealed that most transmission events occurred between teachers and between children within the school. Of the observed household transmission events, most seemed to have originated from a child or teacher who acquired the infection at school. CONCLUSIONS AND RELEVANCE: Despite the implementation of several mitigation measures, the incidence of COVID-19 among children attending primary school in this study was comparable to that observed among teachers and parents. Transmission tree reconstruction suggests that most transmission events originated from within the school. Additional measures should be considered to reduce the transmission of SARS-CoV-2 at school, including intensified testing
Integrated cell type-specific analysis of blood and gut identifies matching eQTL for 140 IBD risk loci and entrectinib as possible repurposing candidate
No full textAbstractGenes whose expression is affected in a consistent manner by GWAS-identified risk variants and the disease process, constitute preferred drug targets. We herein combine integrated cis-eQTL analysis in 27 blood cell populations and 43 intestinal cell types of the ileum, colon and rectum, and information on gene expression in patients, to search for putative drug targets for inflammatory bowel disease (IBD). We detect >95K cis-eQTL that affect >13K e-genes and cluster in >24K regulatory modules (RM). We uncover matching RM for 140 risk loci, implicating >300 e-genes not previously connected to IBD, and find 152 IBD-matching e-genes whose expression is perturbed in the blood or gut of patients. We identify entrectinib, a small molecule inhibiting the NRLP3 inflammasome by binding NEK7, as a promising repurposing candidate for IBD
SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues
No full textVariability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types. © 2021 The Author(s
Mapping the human genetic architecture of COVID-19
No full textnone3597The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19(1,2), host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases(3-7). They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.noneNiemi, Mari E. K.; Karjalainen, Juha; Liao, Rachel G.; Neale, Benjamin M.; Daly, Mark; Ganna, Andrea; Pathak, Gita A.; Andrews, Shea J.; Kanai, Masahiro; Veerapen, Kumar; Fernandez-Cadenas, Israel; Schulte, Eva C.; Striano, Pasquale; Marttila, Minttu; Minica, Camelia; Marouli, Eirini; Karim, Mohd Anisul; Wendt, Frank R.; Savage, Jeanne; Sloofman, Laura; Butler-Laporte, Guillaume; Kim, Han-Na; Kanoni, Stavroula; Okada, Yukinori; Byun, Jinyoung; Han, Younghun; Uddin, Mohammed Jashim; Smith, George Davey; Willer, Cristen J.; Buxbaum, Joseph D.; Mehtonen, Juha; Finucane, Hilary; Cordioli, Mattia; Martin, Alicia R.; Zhou, Wei; Pasaniuc, Bogdan; Julienne, Hanna; Aschard, Hugues; Shi, Huwenbo; Yengo, Loic; Polimanti, Renato; Ghoussaini, Maya; Schwartzentruber, Jeremy; Dunham, Ian; Chwialkowska, Karolina; Francescatto, Margherita; Trankiem, Amy; Balaconis, Mary K.; Davis, Lea; Lee, Sulggi; Priest, James; Renieri, Alessandra; Sankaran, Vijay G.; van Heel, David; Deelen, Patrick; Richards, J. Brent; Nakanishi, Tomoko; Biesecker, Les; Kerchberger, V. Eric; Baillie, J. Kenneth; Mari, Francesca; Bernasconi, Anna; Baillie, Stefano Ceri; Canakoglu, Arif; Wolford, Brooke; Faucon, Annika; Dutta, Atanu Kumar; Schurmann, Claudia; Harry, Emi; Birney, Ewan; Nguyen, Huy; Nasir, Jamal; Kaunisto, Mari; Solomonson, Matthew; Dueker, Nicole; Vadgama, Nirmal; Limou, Sophie; Rahmouni, Souad; Mbarek, Hamdi; Darwish, Dima; Uddin, Md Mesbah; Albertos, Raquel; Pérez-Tur, Jordi; Li, Ruolin; Folkersen, Lasse; Moltke, Ida; Koelling, Nils; Teumer, Alexander; Kousathanas, Athanasios; Utrilla, Alicia; Verdugo, Ricardo A.; Zárate, Ruth; Medina-Gómez, Carolina; Gómez-Cabrero, David; Carnero-Montoro, Elena; Cadilla, Carmen L.; Moreno-Estrada, Andrés; Garmendia, Adriana; Moya, Leire; Sedaghati-Khayat, Bahar; Boua, Palwendé Romuald; Favé, Marie-Julie; Francioli, Laurent; Lemaçon, Audrey; Migeotte, Isabelle; Patel, Sanjay; Varnai, Reka; Szentpeteri, Jozsef L.; Sipeky, Csilla; Colombo, Francesca; von Hohenstaufen, Kathrin; Lio, Pietro; Vallerga, Costanza; Wang, Qingbo; Tanigawa, Yosuke; Im, Hogune; Han, Chulho; Song, Han; Lim, Jiwoo; Lee, Younhe; Kim, Sugyeong; Im, Sangyoon; Atanasovska, Biljana; Ahmad, Hajar Fauzan; Boer, Cindy; Jansen, Philip; Franke, Lude; Kaja, Elżbieta; Pasko, Dorota; Kennis-Szilagyi, Ingrid; Kornilov, Sergey A.; Prijatelj, Vid; Prokić, Ivana; Sivanadhan, Ilangkumaran; Perumal, Sarala; Esmaeeli, Sahar; Pearson, Nathaniel M.; Auton, Adam; Shelton, Janie F.; Shastri, Anjali J.; Filshtein-Sonmez, Teresa; Coker, Daniella; Symons, Antony; Esparza-Gordillo, Jorge; Aslibekyan, Stella; O’Connell, Jared; Ye, Chelsea; Weldon, Catherine H.; Perera, Minoli; O’Leary, Kevin; Tuck, Matthew; O’Brien, Travis; Meltzer, David; O’Donnell, Peter; Nutescu, Edith; Yang, Guang; Alarcon, Cristina; Herrmann, Stefanie; Mazurek, Sophia; Banagan, Jeff; Hamidi, Zacharia; Barbour, April; Raffat, Noora; Moreno, Diana; Friedman, Paula; Ferwerda, Bart; van de Beek, Diederik; Brouwer, Matthijs C.; Vlaar, Alexander P. J.; Wiersinga, W. Joost; Posthuma, Danielle; Tissink, Elleke; Koos Zwinderman, A. H.; Uffelmann, Emil; van Agtmael, Michiel; Algera, Anne Geke; van Baarle, Frank; Bax, Diane; Beudel, Martijn; Jan Bogaard, Harm; Bomers, Marije; Bonta, Peter I.; Bos, Lieuwe; Botta, Michela; de Brabander, Justin; de Bree, Godelieve; de Bruin, Sanne; Bugiani, Marianna; Bulle, Esther; Chouchane, Osoul; Cloherty, Alex; Dongelmans, Dave; Elbers, Paul; Fleuren, Lucas; Geerlings, Suzanne; Geerts, Bart; 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; van Mourik, Niels; Nellen, Jeannine; Nossent, Esther J.; Paulus, Frederique; Peters, Edgar; van der Poll, Tom; Preckel, Bennedikt; Prins, Jan M.; Raasveld, Jorinde; Reijnders, Tom; Schinkel, Michiel; Schultz, Marcus J.; Schuurman, Alex; Sigaloff, Kim; Smit, Marry; Stijnis, Cornelis S.; Stilma, Willemke; Teunissen, Charlotte; Thoral, Patrick; Tsonas, Anissa; van der Valk, Marc; Veelo, Denise; de Vries, Heder; van Vugt, Michèle; Wouters, Dorien; Minnaar, René P.; Kromhout, Adrie; van Uffelen, Kees W. J.; Wolterman, Ruud A.; Roberts, Genevieve; Park, Danny; Ball, Catherine A.; Coignet, Marie; McCurdy, Shannon; Knight, Spencer; Partha, Raghavendran; Rhead, Brooke; Zhang, Miao; Berkowitz, Nathan; Gaddis, Michael; Noto, Keith; Ruiz, Luong; Pavlovic, Milos; Hong, Eurie L.; Rand, Kristin; Girshick, Ahna; Guturu, Harendra; Baltzell, Asher Haug; Rahmouni, Souad; Guntz, Julien; Beguin, Yves; Pigazzini, Sara; Nkambule, Lindokuhle; Bouysran, Youssef; Busson, Adeline; Peyrassol, Xavier; Wilkin, Françoise; Pichon, Bruno; Smits, Guillaume; Vandernoot, Isabelle; Goffard, Jean-Christophe; Georges, Michel; Moutschen, Michel; Misset, Benoit; Darcis, Gilles; Guiot, Julien; Jadot, Laurent; Azarzar, Samira; Dellot, Patricia; Gofflot, Stéphanie; Claassen, Sabine; Bertrand, Axelle; Parzibut, Gilles; Clarinval, Mathilde; Moermans, Catherine; Malaise, Olivier; El Kandoussi, Kamilia; Thonon, Raphaël; Huynen, Pascale; Mesdagh, Alyssia; Melo, Sofia; Jacques, Nicolas; Di Valentin, Emmanuel; Giroule, François; Collignon, Alice; Radermecker, Coraline; Lebrun, Marielle; Perée, Hélène; Latour, Samuel; Barada, Olivia; Sanchez, Judit; Josse, Claire; Boujemla, Bouchra; Meunier, Margot; Mariavelle, Emeline; Anania, Sandy; Gazon, Hélène; Juszczak, Danusia; Fadeur, Marjorie; Camby, Séverine; Meuris, Christelle; Thys, Marie; Jacques, Jessica; Henket, Monique; Léonard, Philippe; Frippiat, Frederic; Giot, Jean-Baptiste; Sauvage, Anne-Sophie; Von Frenckell, Christian; Mni, Myriam; Wéry, Marie; Staderoli, Alicia; Belhaj, Yasmine; Lambermont, Bernard; Morrison, David R.; Mooser, Vincent; Forgetta, Vincenzo; Li, Rui; Ghosh, Biswarup; Laurent, Laetitia; Belisle, Alexandre; Henry, Danielle; Abdullah, Tala; Adeleye, Olumide; Mamlouk, Noor; Kimchi, Nofar; Afrasiabi, Zaman; Rezk, Nardin; Vulesevic, Branka; Bouab, Meriem; Guzman, Charlotte; Petitjean, Louis; Tselios, Chris; Xue, Xiaoqing; Afilalo, Jonathan; Afilalo, Marc; Oliveira, Maureen; Brenner, Bluma; Brassard, Nathalie; Durand, Madeleine; Schurr, Erwin; Lepage, Pierre; Ragoussis, Jiannis; Auld, Daniel; Chassé, Michaël; Kaufmann, Daniel E.; Lathrop, G. Mark; Adra, Darin; Davis, Lea K.; Cox, Nancy J.; Below, Jennifer E.; Sealock, Julia M.; Faucon, Annika B.; Shuey, Megan M.; Polikowsky, Hannah G.; Petty, Lauren E.; Shaw, Douglas M.; Chen, Hung-Hsin; Zhu, Wanying; Ludwig, Kerstin U.; Schröder, Julia; Maj, Carlo; Rolker, Selina; Nöthen, Markus M.; Fazaal, Julia; Keitel, Verena; Jensen, Björn-Erik Ole; Feldt, Torsten; Kurth, Ingo; Marx, Nikolaus; Dreher, Michael; Pink, Isabell; Cornberg, Markus; Illig, Thomas; Lehmann, Clara; Schommers, Philipp; Augustin, Max; Rybniker, Jan; Knopp, Lisa; Eggermann, Thomas; Volland, Sonja; Altmüller, Janine; Berger, Marc M.; Brenner, Thorsten; Hinney, Anke; Witzke, Oliver; Bals, Robert; Herr, Christian; Ludwig, Nicole; Walter, Jörn; Fuchsberger, Christian; Pattaro, Cristian; De Grandi, Alessandro; Pramstaller, Peter; Emmert, David; Melotti, Roberto; Foco, Luisa; Mascalzoni, Deborah; Gögele, Martin; Domingues, Francisco; Hicks, Andrew; Gignoux, Christopher R.; Wicks, Stephen J.; Crooks, Kristy; Barnes, Kathleen C.; Daya, Michelle; Shortt, Jonathan; Rafaels, Nicholas; Chavan, Sameer; Goldstein, David B.; Kiryluk, Krzysztof; Sengupta, Soumitra; Chung, Wendy; Reilly, Muredach P.; Khan, Atlas; Wang, Chen; Povysil, Gundula; Bhardwaj, Nitin; Gharavi, Ali G.; Ionita-Laza, Iuliana; Shang, Ning; O’Byrne, Sheila M.; Nandakumar, Renu; Menon, Amritha; So, Yat S.; Hod, Eldad; Pendrick, Danielle; Kim, Han-Na; Park, Soo-Kyung; Kim, Hyung-Lae; Kang, Chang Kyung; Lee, Hyo-Jung; Song, Kyoung-Ho; Jae Yoon, Kyung; Paik, Nam-Jong; Seok, Woojin; Yoon, Heejun; Joo, Eun-Jeong; Chang, Yoosoo; Ryu, Seungho; Park, Wan Beom; Su Park, Jeong; Un Park, Kyoung; Ham, Sin Young; Jung, Jongtak; Kim, Eu Suk; Kim, Hong Bin; Ellinghaus, David; Degenhardt, Frauke; Cáceres, Mario; Juzenas, Simonas; Lenz, Tobias L.; Albillos, Agustín; Julià, Antonio; Heidecker, Bettina; Garcia, Federico; Kurth, Florian; Tran, Florian; Hanses, Frank; Zoller, Heinz; Holter, Jan C.; Fernández, Javier; Sander, Leif Erik; Rosenstiel, Philip; Koehler, Philipp; de Cid, Rafael; Asselta, Rosanna; Schreiber, Stefan; Hehr, Ute; Prati, Daniele; Baselli, Guido; Valenti, Luca; Bujanda, Luis; Banales, Jesus M.; Duga, Stefano; D’Amato, Mauro; Romero-Gómez, Manuel; Buti, Maria; Invernizzi, Pietro; Franke, Andre; Hov, Johannes R.; Karlsen, Tom H.; Folseraas, Trine; Maya-Miles, Douglas; Teles, Ana; Azuure, Clinton; Wacker, Eike Matthias; Uellendahl-Werth, Florian; ElAbd, Hesham; Arora, Jatin; Lerga-Jaso, Jon; Wienbrandt, Lars; Rühlemann, Malte Christoph; Wendorff, Mareike; Vadla, May Sissel; Lenning, Ole Bernt; Özer, Onur; Myhre, Ronny; Raychaudhuri, Soumya; Tanck, Anja; Gassner, Christoph; Hemmrich-Stanisak, Georg; Kässens, Jan; Figuera Basso, Maria E.; Schulzky, Martin; Wittig, Michael; Braun, Nicole; Wesse, Tanja; Albrecht, Wolfgang; Yi, Xiaoli; Ortiz, Aaron Blandino; Chercoles, Adolfo Garrido; Ruiz, Agustín; Mantovani, Alberto; Holten, Aleksander Rygh; Mayer, Alena; Cherubini, Alessandro; Protti, Alessandro; Aghemo, Alessio; Gerussi, Alessio; Ramirez, Alfredo; Braun, Alice; Barreira, Ana; Lleo, Ana; Kildal, Anders Benjamin; Glück, Andreas; Nolla, Anna Carreras; Latiano, Anna; Dyrhol-Riise, Anne Ma; Muscatello, Antonio; Voza, Antonio; Rando-Segura, Ariadna; Solier, Aurora; Karina, Banasik; Cortes, Beatriz; Mateos, Beatriz; Nafria-Jimenez, Beatriz; Schaefer, Benedikt; Bellinghausen, Carla; Ferrando, Carlos; Quereda, Carmen; Skurk, Carsten; Thibeault, Charlotte; Spinner, Christoph D.; Lange, Christoph; Hu, Cinzia; Cappadona, Claudio; Bianco, Cristiana; Sancho, Cristina; Lihaug Hoff, Dag Arne; Galimberti, Daniela; Jiménez, David; Pestaña, David; Toapanta, David; Azzolini, Elena; Scarpini, Elio; Helbig, Elisa T.; Urrechaga, Eloisa; Paraboschi, Elvezia Maria; Pontali, Emanuele; Reverter, Enric; Navas, Enrique; Arana, Eunate; Sánchez, Félix García; Ceriotti, Ferruccio; Malvestiti, Francesco; Mesonero, Francisco; Pezzoli, Gianni; Lamorte, Giuseppe; Neb, Holger; My, Ilaria; Hernández, Isabel; de Rojas, Itziar; Galván-Femenia, Iván; Heyckendorf, Jan; Rybniker, Jan; Badia, Joan Ramon; Schneider, Jochen; Goikoetxea, Josune; Kraft, Julia; Müller, Karl Erik; Gaede, Karoline I.; Garcia-Etxebarria, Koldo; Tonby, Kristian; Heggelund, Lars; Izquierdo-Sanchez, Laura; Sumoy, Lauro; Lippert, Lena J.; Terranova, Leonardo; Garbarino, Lucia; Téllez, Luis; Roade, Luisa; Ostadreza, Mahnoosh; Intxausti, Maider; Kogevinas, Manolis; Gutiérrez-Stampa, María A.; Vehreschild, Maria J. G. T.; Marquié, Marta; Castoldi, Massimo; Cecconi, Maurizio; Boada, Mercè; Seilmaier, Michael J.; Mazzocco, Michela; Rodríguez-Gandía, Miguel; Ayo, Natale Imaz; Blay, Natalia; Martínez, Nilda; Cornely, Oliver A.; Palmieri, Orazio; Tentorio, Paolo; Rodrigues, Pedro M.; España, Pedro P.; Hoffmann, Per; Bacher, Petra; Suwalski, Phillip; de Pablo, Raúl; Nieto, Rosa; Badalamenti, Salvatore; Ciesek, Sandra; Bombace, Sara; Wilfling, Sibylle; Brunak, Søren; Heilmann-Heimbach, Stefanie; Ripke, Stephan; Bahmer, Thomas; Landmesser, Ulf; Protzer, Ulrike; Rimoldi, Valeria; Skogen, Vegard; Andrade, Victor; Moreno, Victor; Poller, Wolfgang; Farre, Xavier; Wang, Xiaomin; Khodamoradi, Yascha; Karadeniz, Zehra; de Salazar, Adolfo; Palom, Adriana; Garcia-Fernandez, Alba-Estela; Blanco-Grau, Albert; Zanella, Alberto; Bandera, Alessandra; Nebel, Almut; Biondi, Andrea; Caballero-Garralda, Andrea; Gori, Andrea; Lind, Andreas; Fracanzani, Anna Ludovica; Peschuck, Anna; Pesenti, Antonio; de la Horra, Carmen; Milani, Chiara; Paccapelo, Cinzia; Angelini, Claudio; Cea, Cristina; Muñiz-Diaz, Eduardo; Sandoval, Elena; Calderón, Enrique J.; Solligård, Erik; Aziz, Fátima; Martinelli-Boneschi, Filippo; Peyvandi, Flora; Blasi, Francesco; Medrano, Francisco J.; Rodriguez-Frias, Francisco; Müller, Fredrik; Grasselli, Giacomo; Costantino, Giorgio; Cardamone, Giulia; Foti, Giuseppe; Matullo, Giuseppe; Kurihara, Hayato; Afset, Jan Egil; Damås, Jan Kristian; Ampuero, Javier; Martín, Javier; Erdmann, Jeanette; Bergan, Jonas; Goerg, Siegfried; Ferrusquía-Acosta, Jose; Quero, Jose Hernández; Delgado, Juan; Guerrero, Juan M.; Risnes, Kari; Bettini, Laura Rachele; Moreira, Leticia; Gustad, Lise Tuset; Santoro, Luigi; Scudeller, Luigia; Riveiro-Barciela, Mar; Schaefer, Marco; Carrabba, Maria; Valsecchi, Maria G.; Hernandez-Tejero, María; Acosta-Herrera, Marialbert; D’Angiò, Mariella; Baldini, Marina; Cazzaniga, Marina; Ciccarelli, Michele; Bocciolone, Monica; Miozzo, Monica; Chueca, Natalia; Montano, Nicola; Faverio, Paola; Preatoni, Paoletta; Bonfanti, Paolo; Omodei, Paolo; Castro, Pedro; Ferrer, Ricard; Gualtierotti, Roberta; Gallego-Durán, Rocío; Morilla, Rubén; Haider, Sammra; Marsal, Sara; Aneli, Serena; Pelusi, Serena; Bosari, Silvano; Aliberti, Stefano; Dudman, Susanne; Zheng, Tenghao; Pumarola, Tomas; Cejudo, Trinidad Gonzalez; Monzani, Valter; Friaza, Vicente; Peter, Wolfgang; Dopazo, Ximo; Duga, Stefano; May, Sandra; Grimsrud, Marit M.; Gudbjartsson, Daniel F.; Stefansson, Kari; Sulem, Patrick; Sveinbjornsson, Gardar; Melsted, Pall; Norddahl, Gudmundur; Swerford Moore, Kristjan Helgi; Thorsteinsdottir, Unnur; Holm, Hilma; Alarcón-Riquelme, Marta E.; Bernardo, David; Martínez-Bueno, Manuel; Rello, Silvia Rojo; Magi, Reedik; Milani, Lili; Metspalu, Andres; Laisk, Triin; Läll, Kristi; Lepamets, Maarja; Esko, Tõnu; Reimann, Ene; Naaber, Paul; Laane, Edward; Pesukova, Jaana; Peterson, Pärt; Kisand, Kai; Tabri, Jekaterina; Allos, Raili; Hensen, Kati; Starkopf, Joel; Ringmets, Inge; Tamm, Anu; Kallaste, Anne; Alavere, Helene; Metsalu, Kristjan; Puusepp, Mairo; Kristiansson, Kati; Koskelainen, Sami; Perola, Markus; Donner, Kati; Kivinen, Katja; Palotie, Aarno; Palotie, Aarno; Rivolta, Carlo; Bochud, Pierre-Yves; Bibert, Stéphanie; Boillat, Noémie; Nussle, Semira Gonseth; Albrich, Werner; Quinodoz, Mathieu; Kamdar, Dhryata; Suh, Noémie; Neofytos, Dionysios; Erard, Véronique; Voide, Cathy; Bochud, P. Y.; Rivolta, C.; Bibert, S.; Quinodoz, M.; Kamdar, D.; Neofytos, D.; Erard, V.; Voide, C.; Friolet, R.; Vollenweider, P.; Pagani, J. L.; Oddo, M.; zu Bentrup, F. Meyer; Conen, A.; Clerc, O.; Marchetti, O.; Guillet, A.; Guyat-Jacques, C.; Foucras, S.; Rime, M.; Chassot, J.; Jaquet, M.; Viollet, R. Merlet; Lannepoudenx, Y.; Portopena, L.; Desgranges, F.; Filippidis, P.; Guéry, B.; Haefliger, D.; Kampouri, E. E.; Manuel, O.; Munting, A.; Papadimitriou-Olivgeris, M.; Regina, J.; Rochat-Stettler, L.; Suttels, V.; Tadini, E.; Tschopp, J.; Van Singer, M.; Viala, B.; Boillat-Blanco, N.; Brahier, T.; Hügli, O.; Meuwly, J. Y.; Pantet, O.; Nussle, S. Gonseth; Bochud, M.; D’Acremont, V.; Younes, S. Estoppey; Albrich, W. C.; Suh, N.; Cerny, A.; O’Mahony, L.; von Mering, C.; Bochud, P. Y.; Frischknecht, M.; Kleger, G.-R.; Filipovic, M.; Kahlert, C. R.; Wozniak, H.; Negro, T. Rochat; Pugin, J.; Bouras, K.; Knapp, C.; Egger, T.; Perret, A.; Montillier, P.; di Bartolomeo, C.; Barda, B.; de Cid, Rafael; Carreras, Anna; Moreno, Victor; Galván-Femenía, Iván; Blay, Natalia; Farré, Xavier; Sumoy, Lauro; Cortés, Beatriz; Mercader, Josep Maria; Guindo-Martinez, Marta; Torrents, David; Garcia-Aymerich, Judith; Castaño-Vinyals, Gemma; Dobaño, Carlota; Gori, Marco; Renieri, Alessandra; Mondelli, Mario Umberto; Castelli, Francesco; Vaghi, Massimo; Rusconi, Stefano; Montagnani, Francesca; Bargagli, Elena; Franchi, Federico; Mazzei, Maria Antonietta; Cantarini, Luca; Tacconi, Danilo; Feri, Marco; Scala, Raffaele; Spargi, Genni; Nencioni, Cesira; Bandini, Maria; Caldarelli, Gian Piero; Spagnesi, Maurizio; Canaccini, Anna; Ognibene, Agostino; D’Arminio Monforte, Antonella; Girardis, Massimo; Antinori, Andrea; Francisci, Daniela; Schiaroli, Elisabetta; Scotton, Pier Giorgio; Panese, Sandro; Scaggiante, Renzo; Monica, Matteo Della; Capasso, Mario; Fiorentino, Giuseppe; Castori, Marco; Aucella, Filippo; Di Biagio, Antonio; Masucci, Luca; Valente, Serafina; Mandalà, Marco; Zucchi, Patrizia; Giannattasio, Ferdinando; Coviello, Domenico A.; Mussini, Cristina; Bosio, Giancarlo; Tavecchia, Luisa; Crotti, Lia; Rizzi, Marco; La Rovere, Maria Teresa; Sarzi-Braga, Simona; Bussotti, Maurizio; Ravaglia, Sabrina; Artuso, Rosangela; Perrella, Antonio; Romani, Davide; Bergomi, Paola; Catena, Emanuele; Vincenti, Antonella; Ferri, Claudio; Grassi, Davide; Pessina, Gloria; Tumbarello, Mario; Di Pietro, Massimo; Sabrina, Ravaglia; Luchi, Sauro; Barbieri, Chiara; Acquilini, Donatella; Andreucci, Elena; Paciosi, Francesco; Segala, Francesco Vladimiro; Tiseo, Giusy; Falcone, Marco; Lista, Mirjam; Poscente, Monica; De Vivo, Oreste; Petrocelli, Paola; Guarnaccia, Alessandra; Baroni, Silvia; Perticaroli, Valentina; Furini, Simone; Dei, Simona; Benetti, Elisa; Picchiotti, Nicola; Sanarico, Maurizio; Ceri, Stefano; Pinoli, Pietro; Raimondi, Francesco; Biscarini, Filippo; Stella, Alessandra; Bergomi, Mattia; 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Lee, Jon
Whole-genome sequencing reveals host factors underlying critical COVID-19
No full text: Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2-4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease
COVID-19 Host Genetics Initiative. A first update on mapping the human genetic architecture of COVID-19
No full textThe COVID-19 pandemic continues to pose a major public health threat, especially in countries with low vaccination rates. To better understand the biological underpinnings of SARS-CoV-2 infection and COVID-19 severity, we formed the COVID-19 Host Genetics Initiative1. Here we present a genome-wide association study meta-analysis of up to 125,584 cases and over 2.5 million control individuals across 60 studies from 25 countries, adding 11 genome-wide significant loci compared with those previously identified2. Genes at new loci, including SFTPD, MUC5B and ACE2, reveal compelling insights regarding disease susceptibility and severity.</p
