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

• Published in: Cell Vol. 185; no. 5; pp. 916 - 938.e58
• Main Authors: Ai, Zhichao, Ainsworth, Mark, Arancibia-Cárcamo, Carolina V., Attar, Moustafa, Baillie, J. Kenneth, Bashford-Rogers, Rachael, Bicanic, Tihana, Bowness, Paul, Brent, Andrew, Buck, David, Camara, Susana, Clutterbuck, Elizabeth A., Coles, Mark, Conlon, Christopher P., Cribbs, Adam P., Curion, Fabiola, Davenport, Emma E., Davidson, Neil, Davis, Simon, Dendrou, Calliope A., Dequaire, Julie, Docker, James, Dold, Christina, Downes, Damien, Drakesmith, Hal, Dunachie, Susanna J., Espinosa, Alexis, Felle, Sally, Fernandez Mendoza, Maria, Forrow, Aden, Frater, John, Fries, Anastasia, Garner, Lucy C., Godfrey, Leila, Gomez Vazquez, Maria, Green, Angie, Harper, Hong, Heilig, Raphael, Hester, Svenja, Hill, Jennifer, Hinds, Charles, Hird, Clare, Hutton, Paula, Jainarayanan, Ashwin, Jansen, Kathrin, Jones, Elizabeth, Klenerman, Paul, Knight, Julian C., Kumar Sharma, Piyush, Kurupati, Prathiba, Kwok, Andrew, Lee, Angela, Lonie, Lorne, Luo, Jian, Marsden, Brian, Martinez, Jose, Matthews, Philippa C., Mazurczyk, Michalina, McGowan, Simon, Mi, Yuxin, Montadon, Ruddy, O'Brien, Darragh P., Ogg, Graham, Overend, Lauren, Pereira Pinho, Mariana, Perez, Elena, Pollard, Andrew J., Quan, T. Phuong, Revale, Santiago, Silva-Reyes, Laura, Richard, Jean-Baptiste, Rich-Griffin, Charlotte, Salio, Mariolina, Sansom, Stephen Nicholas, Sauka-Spengler, Tatjana, Schwessinger, Ron, Sobrinodiaz, Alberto, Stockdale, Lisa, Strickland, Marie, Sun, Bo, Taylor, Chelsea, Taylor, Stephen, Taylor, Adan, Tomic, Adriana, Tong, Orion, Trebes, Amy, Uhlig, Holm, van Grinsven, Erinke, Vendrell, Iolanda, Verheul, Marije, Wang, Guanlin, Wang, Lihui, Wang, Dapeng, Watkinson, Peter, Watson, Robert, Witty, Lorna, Wray, Katherine, Xue, Luzheng, Young, Rebecca K., Zhang, Ping
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.03.2022; Cell Press
• Subjects: Adult; Biomarkers - blood; blood; Blood Proteins - metabolism; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; coronavirus; COVID-19; COVID-19 - blood; COVID-19 - pathology; COVID-19 - virology; epigenetics; Female; Humans; immune; Influenza, Human - blood; Influenza, Human - pathology; Lymphocytes - immunology; Lymphocytes - metabolism; Machine Learning; Male; Middle Aged; Mitogen-Activated Protein Kinase 14 - genetics; Mitogen-Activated Protein Kinase 14 - metabolism; Monocytes - immunology; Monocytes - metabolism; multi-omics; personalized medicine; Principal Component Analysis; Proteome - analysis; proteomics; Resource; SARS-CoV-2; SARS-CoV-2 - isolation & purification; Sepsis - blood; Sepsis - pathology; Severity of Illness Index; Transcription Factor AP-1 - genetics; Transcription Factor AP-1 - metabolism; transcriptomics; COVID-19; SARS-CoV-2; immune; proteomics; transcriptomics; multi-omics; coronavirus; blood; epigenetics; personalized medicine
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2022.01.012

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. [Display omitted] •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 A multi-omic analysis of patient blood samples reveals both similarities and specific features of COVID-19 when compared with samples obtained from sepsis or influenza patients, which could yield better targeted therapies for severe COVID-19.