A blood atlas of COVID-19 defines hallmarks of disease severity and specificity
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Abstract
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.
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Many studies have characterised complex patterns of viral-induced abnormalities in haematology biochemistry panels.
“Many studies have characterised complex patterns of viral-induced abnormalities in haematology biochemistry panels,18, 19”
From Real-world evaluation of rapid and laboratory-free COVID-19 triage for emergency care: external validation and pilot deployment of artificial intelligence driven screening (2022) · cites this paper as [18]
The Discussion describes complex blood immune and proteomic changes in COVID-19 and influenza, and STAR Methods (Experimental model and subject details; page unavailable) lists routine blood-count and biochemical measurements collected for COVID-19 and sepsis patients. The paper therefore supports viral-associated blood abnormalities, but the cited passages do not show that it characterized complex patterns specifically in routine haematology and biochemistry panels. (LLM, conf=0.78)
Experimental — accuracy not yet measuredSASP-typical cytokines, extracellular matrix-active proteases, and SASP-related pro-coagulant and complement-activating factors are strongly elevated in the serum of COVID-19 patients compared with healthy controls.
“were also strongly elevated in the serum of patients with COVID-19 compared to healthy controls28,52,67–70.”
From COVID-19 and cellular senescence (2023) · cites this paper as [70]
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Research works printed but not linked: 1
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The technological landscape and applications of single-cell multi-omics
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COVID-19 and cellular senescence
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“As this comparison required a new, non-brain reference dataset, we selected PBMCs from healthy donors in the Covid-19 Multi-omics Blood Atlas 34 (COMBAT project; 92,205 annotated cells from 124 non-disease donors).”
- Authors
- 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., 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., 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., & Zurke, Y.-X.
- ORCID
- Ahern, David J.
- Ai, Zhichao
- Ainsworth, Mark
- Allcock, Alice
- Angus, Brian
- Ansari, M. Azim
- Arancibia-Cárcamo, Carolina V.
- Aschenbrenner, Dominik
- Attar, Moustafa
- Baillie, J. Kenneth
- Barnes, Eleanor
- Bashford-Rogers, Rachael
- Beer, Sally
- Bibi, Sagida
- Bicanic, Tihana
- Bowness, Paul
- Brent, Andrew
- Brown, Andrew
- Broxholme, John
- Buck, David
- Burnham, Katie L.
- Byrne, Helen
- Camara, Susana
- Charles, Philip
- Chen, Wentao
- Chen, Yi-Ling
- Chong, Amanda
- Clutterbuck, Elizabeth A.
- Coles, Mark
- Conlon, Christopher P.
- Cornall, Richard
- Cribbs, Adam P.
- Curion, Fabiola
- Davenport, Emma E.
- Davis, Simon
- Dendrou, Calliope A.
- Dib, Lea
- Docker, James
- Dold, Christina
- Dong, Tao
- Downes, Damien
- Drakesmith, Hal
- Dunachie, Susanna J.
- Duncan, David A.
- Eijsbouts, Chris
- Espinosa, Alexis
- Etherington, Rachel
- Fairfax, Benjamin
- Fairhead, Rory
- Fang, Hai
- Fassih, Shayan
- Felle, Sally
- Forrow, Aden
- Frater, John
- Fries, Anastasia
- Garner, Lucy C.
- Geeves, Clementine
- Godfrey, Leila
- Golubchik, Tanya
- Green, Angie
- Harrington, Heather A.
- Heilig, Raphael
- Hester, Svenja
- Hill, Jennifer
- Hinds, Charles
- Ho, Ling-Pei
- Hoekzema, Renee
- Hughes, Jim
- Hutton, Paula
- Jainarayanan, Ashwin
- James-Bott, Anna
- Jansen, Kathrin
- Jeffery, Katie
- Jones, Elizabeth
- Kim, David
- Klenerman, Paul
- Knight, Julian C.
- Kumar, Vinod
- Kurupati, Prathiba
- Kwok, Andrew
- Lee, Angela
- Linder, Aline
- Lopopolo, Maria
- Lukoseviciute, Martyna
- Luo, Jian
- Marinou, Spyridoula
- Marsden, Brian
- Matthews, Philippa C.
- Mazurczyk, Michalina
- McGowan, Simon
- McKechnie, Stuart
- Mead, Adam
- Mentzer, Alexander J.
- Mi, Yuxin
- Monaco, Claudia
- Napolitani, Giorgio
- Nassiri, Isar
- Novak, Alex
- O'Brien, Darragh P.
- Ogg, Graham
- Overend, Lauren
- Park, Inhye
- Pavord, Ian
- Peng, Yanchun
- Penkava, Frank
- Pollard, Andrew J.
- Powrie, Fiona
- Psaila, Bethan
- Quan, T. Phuong
- Repapi, Emmanouela
- Revale, Santiago
- Silva-Reyes, Laura
- Richard, Jean-Baptiste
- Rollier, Christine S.
- Rowland, Matthew
- Ruehle, Fabian
- Salio, Mariolina
- Sansom, Stephen Nicholas
- Schwessinger, Ron
- Screaton, Gavin
- Seigal, Anna
- Semple, Malcolm G.
- Sergeant, Martin
- Sims, David
- Skelly, Donal
- Slawinski, Hubert
- Sousos, Nikolaos
- Stafford, Lizzie
- Stockdale, Lisa
- Strickland, Marie
- Sumray, Otto
- Sun, Bo
- Taylor, Chelsea
- Taylor, Stephen
- Thongjuea, Supat
- Todd, John A.
- Tong, Orion
- Trebes, Amy
- Tucci, Felicia Anna
- Turtle, Lance
- Udalova, Irina
- Uhlig, Holm
- Vendrell, Iolanda
- Voda, Alexandru
- Wang, Guanlin
- Wang, Lihui
- Wang, Dapeng
- Watkinson, Peter
- Watson, Robert
- Weinberger, Michael
- Whalley, Justin
- Xue, Luzheng
- Yeung, Hing Yuen
- Yin, Zixi
- Young, Rebecca K.
- Youngs, Jonathan
- Zhang, Ping
- Zurke, Yasemin-Xiomara
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2022-03
- Volume
- 185
- Issue
- 5
- Pages
- 916-938.e58
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC8776501
- OpenAlex
- W4220939068
- Cited by
- 328
- References
- 155
- Citations by year
- 2026: 37 · 2025: 62 · 2024: 71 · 2023: 99 · 2022: 52 · 2021: 7
- FWCI
- 35.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell (publishedVersion, cc-by)
- medRxiv (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- VU Research Portal (publishedVersion, other-oa)
- CentAUR (University of Reading) (acceptedVersion)
- St George's Online Research Archive (St George's University of London) (acceptedVersion)
- Research Portal (King's College London) (submittedVersion, cc-by)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by)
- Funders
- Chinese Academy of Medical Sciences (CRUK C130623/A249471, IFMS 2018-I2M-2-002)
- National Institutes of Health (U192U19AI082630 R24DK106766)
- Gilead Sciences (KENN151612 KENN192004 KENN171803)
- Engineering and Physical Sciences Research Council (EP/R018472/1 EP/R005125/1 EP/T001968/1)
- National Institute for Health Research
- Wellcome Trust
- UK Research and Innovation (MR/S005471/1)
- Medical Research Council (MCUU00016/14 12009/14 MR/S035850/1 MCPC19059)
- Kennedy Trust for Rheumatology Research
- University of Oxford
- Rosetrees Trust
- Chinese Academy of Sciences
- British Heart Foundation
- United Kingdom Department of Health and Social Care
- Royal Society
- Cancer Research UK
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Keywords
- COVID-19 pandemic, disease severity, multi-omics, immune signatures, immune activation, plasma proteome, patient phenotyping, influenza, sepsis, immune repertoire, coagulation, acute phase response, immunometabolism, tensor decomposition, matrix factorization
- MeSH terms
- Machine Learning, COVID-19, SARS-CoV-2, Adult, Blood Proteins, Female, Humans, Influenza, Human, Lymphocytes, Male, Middle Aged, Monocytes, Severity of Illness Index, Biomarkers, Cell Cycle Proteins, Sepsis, Transcription Factor AP-1, Proteome, Principal Component Analysis, Mitogen-Activated Protein Kinase 14
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