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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.