학술논문
A blood atlas of COVID-19 defines hallmarks of disease severity and specificity
Document Type
Report
Author
Ahern, David J.; Ai, Zhichao; Ainsworth, Mark; Allan, Chris; Allcock, Alice; Angus, Brian; Ansari, M. Azim; Arancibia-Cárcamo, Carolina V.; Aschenbrenner, Dominik; Attar, Moustafa; Baillie, J. Kenneth; Barnes, Eleanor; 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 L.; Byrne, Helen; Camara, Susana; Candido Ferreira, Ivan; Charles, Philip; Chen, Wentao; Chen, Yi-Ling; Chong, Amanda; Clutterbuck, Elizabeth A.; Coles, Mark; Conlon, Christopher P.; Cornall, Richard; Cribbs, Adam P.; Curion, Fabiola; Davenport, Emma E.; Davidson, Neil; Davis, Simon; Dendrou, Calliope A.; Dequaire, Julie; Dib, Lea; Docker, James; Dold, Christina; Dong, Tao; Downes, Damien; Drakesmith, Hal; Dunachie, Susanna J.; Duncan, David A.; Eijsbouts, Chris; Esnouf, Robert; Espinosa, Alexis; Etherington, Rachel; Fairfax, Benjamin; Fairhead, Rory; Fang, Hai; Fassih, Shayan; Felle, Sally; Fernandez Mendoza, Maria; Ferreira, Ricardo; Fischer, Roman; Foord, Thomas; Forrow, Aden; Frater, John; Fries, Anastasia; Gallardo Sanchez, Veronica; Garner, Lucy C.; Geeves, Clementine; Georgiou, Dominique; Godfrey, Leila; Golubchik, Tanya; Gomez Vazquez, Maria; Green, Angie; Harper, Hong; Harrington, Heather A.; Heilig, Raphael; Hester, Svenja; Hill, Jennifer; Hinds, Charles; Hird, Clare; Ho, Ling-Pei; Hoekzema, Renee; Hollis, Benjamin; Hughes, Jim; Hutton, Paula; Jackson-Wood, Matthew A.; Jainarayanan, Ashwin; James-Bott, Anna; Jansen, Kathrin; Jeffery, Katie; Jones, Elizabeth; Jostins, Luke; Kerr, Georgina; Kim, David; Klenerman, Paul; Knight, Julian C.; Kumar, Vinod; Kumar Sharma, Piyush; Kurupati, Prathiba; Kwok, Andrew; Lee, Angela; Linder, Aline; Lockett, Teresa; Lonie, Lorne; Lopopolo, Maria; Lukoseviciute, Martyna; Luo, Jian; Marinou, Spyridoula; Marsden, Brian; Martinez, Jose; Matthews, Philippa C.; Mazurczyk, Michalina; McGowan, Simon; McKechnie, Stuart; Mead, Adam; Mentzer, Alexander J.; Mi, Yuxin; Monaco, Claudia; Montadon, Ruddy; Napolitani, Giorgio; Nassiri, Isar; Novak, Alex; O'Brien, Darragh P.; O'Connor, Daniel; O'Donnell, Denise; Ogg, Graham; Overend, Lauren; Park, Inhye; Pavord, Ian; Peng, Yanchun; Penkava, Frank; Pereira Pinho, Mariana; Perez, Elena; Pollard, Andrew J.; Powrie, Fiona; Psaila, Bethan; Quan, T. Phuong; Repapi, Emmanouela; Revale, Santiago; Silva-Reyes, Laura; Richard, Jean-Baptiste; Rich-Griffin, Charlotte; Ritter, Thomas; Rollier, Christine S.; Rowland, Matthew; Ruehle, Fabian; Salio, Mariolina; Sansom, Stephen Nicholas; Sanches Peres, Raphael; Santos Delgado, Alberto; Sauka-Spengler, Tatjana; Schwessinger, Ron; Scozzafava, Giuseppe; Screaton, Gavin; Seigal, Anna; Semple, Malcolm G.; Sergeant, Martin; Simoglou Karali, Christina; Sims, David; Skelly, Donal; Slawinski, Hubert; Sobrinodiaz, Alberto; Sousos, Nikolaos; Stafford, Lizzie; Stockdale, Lisa; Strickland, Marie; Sumray, Otto; Sun, Bo; Taylor, Chelsea; Taylor, Stephen; Taylor, Adan; Thongjuea, Supat; Thraves, Hannah; Todd, John A.; Tomic, Adriana; Tong, Orion; Trebes, Amy; Trzupek, Dominik; Tucci, Felicia Anna; Turtle, Lance; Udalova, Irina; Uhlig, Holm; van Grinsven, Erinke; Vendrell, Iolanda; Verheul, Marije; Voda, Alexandru; Wang, Guanlin; Wang, Lihui; Wang, Dapeng; Watkinson, Peter; Watson, Robert; Weinberger, Michael; Whalley, Justin; Witty, Lorna; Wray, Katherine; Xue, Luzheng; Yeung, Hing Yuen; Yin, Zixi; Young, Rebecca K.; Youngs, Jonathan; Zhang, Ping; Zurke, Yasemin-Xiomara
Source
Cell. March 3, 2022, Vol. 185 Issue 5, 916
Subject
Language
English
ISSN
0092-8674
Abstract
Keywords coronavirus; SARS-CoV-2; COVID-19; blood; immune; transcriptomics; epigenetics; proteomics; multi-omics; personalized medicine Highlights * Blood atlas delineating innate and adaptive immune dysregulation in COVID-19 * Shared and specific immune signatures of COVID-19, influenza and all cause sepsis * Multi-omic immune profiling differentiates hospitalized patient severity in COVID-19 * Immune activation and proliferation involving AP-1/p38MAPK associated with COVID-19 Summary 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. * Corresponding author Article History: Received 5 May 2021; Revised 16 August 2021; Accepted 17 January 2022 (miscellaneous) Published: January 21, 2022 (footnote)1 Further details can be found in the supplemental information (footnote)2 Lead contact (Julian C. Knight) Byline: David J. 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, Georgina Berridge, Amy Beveridge, Sagida Bibi, Tihana Bicanic, Luke Blackwell, Paul Bowness, Andrew Brent, Andrew Brown, John Broxholme, David Buck, Katie L. Burnham, Helen Byrne, Susana Camara, Ivan Candido Ferreira, Philip Charles, Wentao Chen, Yi-Ling Chen, Amanda Chong, Elizabeth A. Clutterbuck, Mark Coles, Christopher P. Conlon, Richard 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 Downes, Hal Drakesmith, Susanna J. Dunachie, David A. Duncan, Chris Eijsbouts, Robert Esnouf, Alexis Espinosa, Rachel Etherington, Benjamin Fairfax, Rory Fairhead, Hai Fang, Shayan Fassih, Sally Felle, Maria Fernandez Mendoza, Ricardo Ferreira, Roman Fischer, Thomas Foord, Aden Forrow, John Frater, Anastasia Fries, Veronica Gallardo Sanchez, 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 Hoekzema, Benjamin Hollis, Jim 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 Marsden, Jose Martinez, Philippa C. Matthews, Michalina Mazurczyk, Simon McGowan, Stuart McKechnie, Adam 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 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 Nicholas Sansom, Raphael Sanches Peres, Alberto Santos Delgado, Tatjana Sauka-Spengler, Ron Schwessinger, Giuseppe Scozzafava, Gavin Screaton, Anna Seigal, Malcolm G. Semple, Martin 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, Adan Taylor, Supat Thongjuea, Hannah Thraves, John A. Todd, Adriana Tomic, Orion Tong, Amy Trebes, Dominik Trzupek, Felicia Anna Tucci, Lance Turtle, Irina Udalova, Holm Uhlig, Erinke van Grinsven, Iolanda Vendrell, Marije Verheul, Alexandru Voda, Guanlin Wang, Lihui Wang, Dapeng Wang, Peter Watkinson, Robert Watson, Michael Weinberger, Justin Whalley, Lorna Witty, Katherine Wray, Luzheng Xue, Hing Yuen Yeung, Zixi Yin, Rebecca K. Young, Jonathan Youngs, Ping Zhang, Yasemin-Xiomara Zurke