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

Author

COvid-19 Multi-omics Blood ATlas (COMBAT) Consortium

Ahern, D

Ai, Z

Ainsworth, M

Allan, C

Allcock, A

Ansari, A

Arancibia-Carcamo, C

Aschenbrenner, D

Attar, M

Baillie, K

Barnes, E

Bashford-Rogers, R

Bashyal, A

Beer, S

Berridge, G

Beveridge, A

Bibi, S

Bicanic, T

Blackwell, L

Bowness, P

Brent, A

Brown, A

Broxholme, J

Buck, D

Burnham, K

Byrne, H

Camara, S

Candido Ferreira, I

Charles, P

Chen, W

Chen, Y

Chong, A

Clutterbuck, E

Coles, M

Conlon, C

Cornall, R

Cribbs, A

Curion, F

Davenport, E

Davidson, N

Davis, S

Dendrou, C

Dequaire, J

Dib, L

Docker, J

Dold, C

Dong, T

Downes, D

Drakesmith, A

Dunachie, S

Duncan, D

Eijsbouts, C

Esnouf, R

Espinosa, A

Etherington, R

Fairfax, B

Fairhead, R

Fang, H

Fassih, S

Felle, S

Fernandez Mendoza, M

Ferreira, R

Fischer, R

Foord, T

Forrow, A

Frater, J

Fries, A

Gallardo Sanchez, V

Garner, L

Geeves, C

Georgiou, D

Godfrey, L

Golubchik, T

Gomez Vazquez, M

Green, A

Harper, H

Harrington, H

Heilig, R

Hester, S

Hill, J

Hinds, C

Hird, C

Ho, L

Hoekzema, R

Hollis, B

Hughes, J

Hutton, P

Jackson, M

Jainarayanan, A

James-Bott, A

Jansen, K

Jeffery, K

Jones, E

Jostins, L

Kerr, G

Kim, D

Klenerman, P

Knight, J

Kumar, V

Kumar Sharma, P

Kurupati, P

Kwok, A

Lee, A

Linder, A

Lockett, T

Lonie, L

Lopopolo, M

Lukoseviciute, M

Luo, J

Marinou, S

Marsden, B

Martinez, J

Matthews, P

Mazurczyk, M

McGowan, S

McKechnie, S

Mead, A

Mentzer, A

Mi, Y

Monaco, C

Montadon, R

Napolitani, G

Nassiri, I

Novak, A

O'Brien, D

O'Connor, D

O'Donnell, D

Ogg, G

Overend, L

Park, I

Pavord, I

Peng, Y

Penkava, F

Pereira Pinho, M

Perez, E

Pollard, A

Powrie, F

Psaila, B

Quan, P

Repapi, E

Revale, S

Silva-Reyes, L

Richard, J

Rich-Griffin, C

Ritter, T

Rollier, C

Rowland, M

Ruehle, F

Salio, M

Sansom, S

Santos Delgado, A

Sauka-Spengler, T

Schwessinger, R

Scozzafava, G

Screaton, G

Seigal, A

Semple, M

Sergeant, M

Simoglou Karali, C

Sims, D

Skelly, D

Slawinski, H

Sobrinodiaz, A

Sousos, N

Stafford, L

Stockdale, L

Strickland, M

Sumray, O

Sun, B

Taylor, C

Taylor, S

Taylor, A

Thongjuea, S

Thraves, H

Todd, J

Tomic, A

Tong, O

Trebes, A

Trzupek, D

Tucci, F

Turtle, L

Udalova, I

Uhlig, H

van Grinsven, E

Vendrell, I

Verheul, M

Voda, A

Wang, G

Wang, L

Wang, D

Watkinson, P

Watson, R

Weinberger, M

Whalley, J

Witty, L

Wray, K

Xue, L

Yeung, H

Yin, Z

Young, R

Youngs, J

Zhang, P

Zurke, Y

DOI

10.1101/2021.05.11.21256877

Last updated

2022-10-06T21:24:44.963+01:00

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.

Symplectic ID

1176194

Submitted to ORA

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Publication type

59

Publication date

11 May 2021