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A blood atlas of COVID-19 defines hallmarks of disease severity and specificity

2022; Cell Press; Volume: 185; Issue: 5 Linguagem: Inglês

10.1016/j.cell.2022.01.012

1097-4172

David Ahern, Zhichao Ai, Mark Ainsworth, Chris Allan, Alice Allcock, Brian Angus, M. Azim Ansari, Carolina V. Arancibia-Cárcamo, Dominik Aschenbrenner, Moustafa Attar, J. Kenneth Baillie, Eleanor Barnes, Rachael Bashford-Rogers, Archana Bashyal, Sally Beer, G. Berridge, Amy Beveridge, Sagida Bibi, Tihana Bicanic, Luke Blackwell, Paul Bowness, Andrew Brent, Andrew Brown, John Broxholme, David Buck, Katie L. Burnham, Helen M. Byrne, Susana Camara, Ivan Candido-Ferreira, Philip D. Charles, Wentao Chen, Yi‐Ling Chen, Amanda Y. Chong, Elizabeth Clutterbuck, Mark Coles, Christopher P. Conlon, Richard J. Cornall, Adam P. Cribbs, Fabiola Curion, Emma E. Davenport, Neil Davidson, Simon Davis, Calliope A. Dendrou, Julie Dequaire, Lea Dib, James Docker, Christina Dold, Tao Dong, Damien J. Downes, Hal Drakesmith, Susanna Dunachie, David A. Duncan, Chris Eijsbouts, Robert Esnouf, Alexis Espinosa, Rachel Etherington, Benjamin P. Fairfax, Rory Fairhead, Hai Fang, Shayan Fassih, Sally Felle, Maria Fernandez Mendoza, Ricardo Melo Ferreira, Román Fischer, Thomas Foord, Aden Forrow, John Frater, Anastasia Fries, Verónica Sánchez, Lucy C. Garner, Clementine Geeves, Dominique Georgiou, Leila Godfrey, Tanya Golubchik, Maria Gomez Vazquez, Angie Green, Hong Harper, Heather A. Harrington, Raphael Heilig, Svenja Hester, Jennifer Hill, Charles Hinds, Clare Hird, Ling‐Pei Ho, Renee S. Hoekzema, Benjamin Hollis, Jim R. Hughes, Paula Hutton, Matthew A. Jackson-Wood, Ashwin Jainarayanan, Anna James-Bott, Kathrin Jansen, Katie Jeffery, Elizabeth Jones, Luke Jostins, Georgina Kerr, David Kim, Paul Klenerman, Julian C. Knight, Vinod Kumar, Piyush Kumar Sharma, Prathiba Kurupati, Andrew Kwok, Angela Lee, Aline Linder, Teresa Lockett, Lorne Lonie, Maria Lopopolo, Martyna Lukoseviciute, Jian Luo, Spyridoula Marinou, Brian D. Marsden, Jose Martinez, Philippa C. Matthews, Michalina Mazurczyk, Simon J. McGowan, Stuart McKechnie, Adam J. Mead, Alexander J. Mentzer, Yuxin Mi, Claudia Monaco, Ruddy Montadon, Giorgio Napolitani, Isar Nassiri, Alex Novak, Darragh P. O’Brien, Daniel O’Connor, Denise O’Donnell, Graham S. Ogg, Lauren Overend, Inhye Park, Ian Pavord, Yanchun Peng, Frank Penkava, Mariana Pereira Pinho, Elena Perez, Andrew J. Pollard, Fiona Powrie, Bethan Psaila, T. Phuong Quan, Emmanouela Repapi, Santiago Revale, Laura Silva-Reyes, Jean-Baptiste Richard, Charlotte Rich-Griffin, Thomas Ritter, Christine S. Rollier, Matthew Rowland, Fabian Ruehle, Mariolina Salio, Stephen N. Sansom, Raphael Sanches Peres, Alberto Santos Delgado, Tatjana Sauka‐Spengler, Ron Schweßinger, Giuseppe Scozzafava, Gavin Screaton, Anna Seigal, Malcolm G. Semple, Martin J. Sergeant, Christina Simoglou Karali, David Sims, Donal Skelly, Hubert Slawinski, Alberto Sobrinodiaz, Nikolaos Sousos, Lizzie Stafford, Lisa Stockdale, Marie Strickland, Otto Sumray, Bo Sun, Chelsea Taylor, Stephen Taylor, A Taylor, Supat Thongjuea, Hannah Thraves, John A. Todd, Adriana Tomić, Orion Tong, Amy Trebes, Dominik Trzupek, Felicia Anna Tucci, Lance Turtle, Irina A. Udalova, Holm H. Uhlig, Erinke van Grinsven, Iolanda Vendrell, Marije K. Verheul, Alexandru-Ioan Voda, Guanlin Wang, Lihui Wang, Dapeng Wang, Peter Watkinson, Robert Watson, Michael Weinberger, Justin P. Whalley, Lorna Witty, Katherine Wray, Luzheng Xue, Hing‐Yuen Yeung, Zixi Yin, Rebecca Young, Jonathan Youngs, Ping Zhang, Yasemin-Xiomara Zurke,

Long-Term Effects of COVID-19

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, 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. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design, and personalized medicine approaches for COVID-19.