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

Ahern, D. J., Ai, Z., Ainsworth, M., Allan, C., Allcock, A., Angus, B., Ansari, M. A., Arancibia-Cárcamo, C. V., Aschenbrenner, D., Attar, M., Baillie, J. 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. L., Byrne, H., Camara, S., Candido Ferreira, I., Charles, P., Chen, W., Chen, Y.-L., Chong, A., Clutterbuck, E. A., Coles, M., Conlon, C. P., Cornall, R., Cribbs, A. P., Curion, F., Davenport, E. E., Davidson, N., Davis, S., Dendrou, C. A., Dequaire, J., Dib, L. ORCID: https://orcid.org/0000-0001-5889-4738, Docker, J., Dold, C., Dong, T., Downes, D., Drakesmith, H., Dunachie, S. J., Duncan, D. A., 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. C., Geeves, C., Georgiou, D., Godfrey, L., Golubchik, T., Gomez Vazquez, M., Green, A., Harper, H., Harrington, H. A., Heilig, R., Hester, S., Hill, J., Hinds, C., Hird, C., Ho, L.-P., Hoekzema, R., Hollis, B., Hughes, J., Hutton, P., Jackson-Wood, M. A., Jainarayanan, A., James-Bott, A., Jansen, K., Jeffery, K., Jones, E., Jostins, L., Kerr, G., Kim, D., Klenerman, P., Knight, J. C. ORCID: https://orcid.org/0000-0002-0377-5536, 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. C., Mazurczyk, M., McGowan, S., McKechnie, S., Mead, A., Mentzer, A. J., Mi, Y., Monaco, C., Montadon, R., Napolitani, G., Nassiri, I., Novak, A., O'Brien, D. P., 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. J., Powrie, F., Psaila, B., Quan, T. P., Repapi, E., Revale, S., Silva-Reyes, L., Richard, J.-B., Rich-Griffin, C., Ritter, T., Rollier, C. S., Rowland, M., Ruehle, F., Salio, M., Sansom, S. N., Sanches Peres, R., Santos Delgado, A., Sauka-Spengler, T., Schwessinger, R., Scozzafava, G., Screaton, G., Seigal, A., Semple, M. G., 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. A., Tomic, A., Tong, O., Trebes, A., Trzupek, D., Tucci, F. A., 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. Y., Yin, Z., Young, R. K., Youngs, J., Zhang, P. and Zurke, Y.-X. (2022) A blood atlas of COVID-19 defines hallmarks of disease severity and specificity. Cell, 185 (5). pp. 916-938. ISSN 1097-4172 doi: 10.1016/j.cell.2022.01.012 (e58)

Abstract/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.

Item Type	Article
URI	https://centaur.reading.ac.uk/id/eprint/123311
Identification Number/DOI	10.1016/j.cell.2022.01.012
Refereed	Yes
Divisions	Life Sciences > School of Biological Sciences > Biomedical Sciences
Publisher	Elsevier
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