A blood atlas of COVID-19 defines hallmarks of disease severity and specificity
Authors:   COvid-19 Multi-omics Blood ATlas (COMBAT) Consortium, Ahern David J , Ai Zhichao , Ainsworth Mark , Allan Chris , Allcock Alice , Ansari Azim , Arancibia-Carcamo 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 , Coles Mark , Conlon Christopher P , Cornall Richard , Cribbs Adam P , Curion Fabiola , Davenport Emma E , Davidson Neil , Davis Simon , Dendrou Calliope , Dequaire Julie , Dib Lea , Docker James , Dold Christina , Dong Tao , Downes Damien , Drakesmith Alexander , 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 , 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 Matthew , 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 , 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 , 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 N , 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 A , 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 
Published: May 2021

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.