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COvid-19 Multi-omics Blood ATlas (COMBAT) Consortium, , Ahern, David, Ai, Zhichao, Ainsworth, Mark, Allan, Chris, Allcock, Alice, Ansari, Azim 
ORCID: 0000-0003-2790-8353, Arancibia-Carcamo, Carolina, Aschenbrenner, Dominik, Attar, Moustafa ORCID: 0000-0003-4116-1276 et al (show 194 more authors) , Baillie, Kenneth, Barnes, Eleanor ORCID: 0000-0002-0860-0831, Bashford-Rogers, Rachael, Bashyal, Archana, Beer, Sally, Berridge, Georgina, Beveridge, Amy, Bibi, Sagida, Bicanic, Tihana, Blackwell, Luke, Bowness, Paul, Brent, Andrew, Brown, Andrew, Broxholme, John, Buck, David, Burnham, Katie, Byrne, Helen, Camara, Susana, Candido Ferreira, Ivan ORCID: 0000-0002-4916-4212, Charles, Philip, Chen, Wentao, Chen, Yi-Ling, Chong, Amanda, Clutterbuck, Elizabeth, Coles, Mark, Conlon, Christopher, Cornall, Richard, Cribbs, Adam, Curion, Fabiola ORCID: 0000-0003-2502-8803, Davenport, Emma, Davidson, Neil, Davis, Simon, Dendrou, Calliope, Dequaire, Julie, Dib, Lea, Docker, James, Dold, Christina, Dong, Tao, Downes, Damien, Drakesmith, Alexander, Dunachie, Susanna ORCID: 0000-0001-5665-6293, Duncan, David, Eijsbouts, Chris, Esnouf, Robert, Espinosa, Alexis, Etherington, Rachel, Fairfax, Benjamin, Fairhead, Rory ORCID: 0000-0001-7157-3015, Fang, Hai, Fassih, Shayan, Felle, Sally, Fernandez Mendoza, Maria, Ferreira, Ricardo, Fischer, Roman, Foord, Thomas, Forrow, Aden, Frater, John ORCID: 0000-0001-7163-7277, Fries, Anastasia, Gallardo Sanchez, Veronica, Garner, Lucy, Geeves, Clementine, Georgiou, Dominique, Godfrey, Leila, Golubchik, Tanya, Gomez Vazquez, Maria, Green, Angie, Harper, Hong, Harrington, Heather, Heilig, Raphael, Hester, Svenja, Hill, Jennifer, Hinds, Charles, Hird, Clare, Ho, Ling-Pei ORCID: 0000-0001-8319-301X, Hoekzema, Renee, Hollis, Benjamin, Hughes, Jim, Hutton, Paula, Jackson, Matthew, Jainarayanan, Ashwin, James-Bott, Anna, Jansen, Kathrin, Jeffery, Katie, Jones, Elizabeth, Jostins, Luke, Kerr, Georgina, Kim, David, Klenerman, Paul ORCID: 0000-0003-4307-9161, Knight, Julian ORCID: 0000-0002-0377-5536, Kumar, Vinod, Kumar Sharma, Piyush, Kurupati, Prathiba, Kwok, Andrew, Lee, Angela, Linder, Aline, Lockett, Teresa, Lonie, Lorne, Lopopolo, Maria, Lukoseviciute, Martyna ORCID: 0000-0002-8915-5249, Luo, Jian, Marinou, Spyridoula, Marsden, Brian, Martinez, Jose, Matthews, Philippa, Mazurczyk, Michalina, McGowan, Simon, McKechnie, Stuart, Mead, Adam, Mentzer, Alexander, Mi, Yuxin, Monaco, Claudia, Montadon, Ruddy, Napolitani, Giorgio, Nassiri, Isar, Novak, Alex, O'Brien, Darragh, O'Connor, Daniel ORCID: 0000-0002-6902-9886, O'Donnell, Denise, Ogg, Graham ORCID: 0000-0002-3097-045X, Overend, Lauren, Park, Inhye, Pavord, Ian, Peng, Yanchun, Penkava, Frank, Pereira Pinho, Mariana, Perez, Elena, Pollard, Andrew, Powrie, Fiona, Psaila, Bethan, Quan, Phuong, Repapi, Emmanouela, Revale, Santiago, Silva-Reyes, Laura, Richard, Jean-Baptiste, Rich-Griffin, Charlotte, Ritter, Thomas, Rollier, Christine, Rowland, Matthew, Ruehle, Fabian, Salio, Mariolina, Sansom, Stephen, Santos Delgado, Alberto, Sauka-Spengler, Tatjana, Schwessinger, Ron, Scozzafava, Giuseppe, Screaton, Gavin, Seigal, Anna, Semple, Malcolm ORCID: 0000-0001-9700-0418, Sergeant, Martin, Simoglou Karali, Christina, Sims, David, Skelly, Donal ORCID: 0000-0002-2426-3097, Slawinski, Hubert, Sobrinodiaz, Alberto, Sousos, Nikolaos ORCID: 0000-0002-9100-2954, Stafford, Lizzie ORCID: 0000-0002-1610-5136, Stockdale, Lisa, Strickland, Marie, Sumray, Otto, Sun, Bo, Taylor, Chelsea, Taylor, Stephen, Taylor, Adan, Thongjuea, Supat, Thraves, Hannah, Todd, John ORCID: 0000-0003-2740-8148, Tomic, Adriana, Tong, Orion, Trebes, Amy, Trzupek, Dominik, Tucci, Felicia, Turtle, Lance ORCID: 0000-0002-0778-1693, Udalova, Irina, Uhlig, Holm ORCID: 0000-0002-6111-7355, van Grinsven, Erinke, Vendrell, Iolanda, Verheul, Marije, Voda, Alexandru ORCID: 0000-0003-2974-6992, Wang, Guanlin, Wang, Lihui, Wang, Dapeng, Watkinson, Peter, Watson, Robert, Weinberger, Michael, Whalley, Justin ORCID: 0000-0002-0403-3091, Witty, Lorna, Wray, Katherine, Xue, Luzheng, Yeung, Hing Yuen, Yin, Zixi, Young, Rebecca, Youngs, Jonathan, Zhang, Ping and Zurke, Yasemin-Xiomara
(2021)
A blood atlas of COVID-19 defines hallmarks of disease severity and specificity.
medRxiv.
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Abstract
<h4>Summary</h4> Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete understanding of potentially druggable immune mediators of disease. To advance this, we present a comprehensive multi-omic blood atlas in patients with varying COVID-19 severity and compare with influenza, sepsis and healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity revealed cells, their inflammatory mediators and networks as potential therapeutic targets, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Tensor and matrix decomposition of the overall dataset revealed feature groupings linked with disease severity and specificity. Our systems-based integrative approach and blood atlas will inform future drug development, clinical trial design and personalised medicine approaches for COVID-19.
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