A blood atlas of COVID-19 defines hallmarks of disease severity and specificity
Ahern DJ., Ai Z., Ainsworth M., Allan C., Allcock A., Ansari A., Arancibia-Carcamo CV., Aschenbrenner D., Attar M., Baillie JK., 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 KL., Byrne H., Camara S., Candido Ferreira I., Charles P., Chen W., Chen Y-L., Chong A., Clutterbuck E., Coles M., Conlon CP., Cornall R., Cribbs AP., Curion F., Davenport EE., Davidson N., Davis S., Dendrou C., Dequaire J., Dib L., Docker J., Dold C., Dong T., Downes D., Drakesmith A., Dunachie SJ., Duncan DA., 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 HA., Heilig R., Hester S., Hill J., Hinds C., Hird C., Ho L-P., 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 JC., 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 AJ., 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 AJ., Powrie F., Psaila B., Quan TP., Repapi E., Revale S., Silva-Reyes L., Richard J-B., Rich-Griffin C., Ritter T., Rollier CS., Rowland M., Ruehle F., Salio M., Sansom SN., Santos Delgado A., Sauka-Spengler T., Schwessinger R., Scozzafava G., Screaton G., Seigal A., Semple MG., 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 JA., Tomic A., Tong O., Trebes A., Trzupek D., Tucci FA., 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 HY., Yin Z., Young RK., Youngs J., Zhang P., Zurke Y-X.
SummaryTreatment 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.