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

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

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)916-938.e58
Number of pages82
JournalCell
Volume185
Issue number5
DOIs
Publication statusPublished - 3 Mar 2022
Externally publishedYes

Bibliographical note

Funding Information:
Research supported by the University of Oxford COVID-19 Research Response Fund and NIHR Oxford Biomedical Research Centre. Work of contributing authors supported by grants (Data S1) including BHF RG/13/9/303269 FS/18/63/34184; CAMS IFMS 2018-I2M-2-002; CRUK C130623/A249471; EPSRC EP/R018472/1 EP/R005125/1 EP/T001968/1; Emerson Collective; Gilead; Huo Family Foundation; Kennedy Trust for Rheumatology Research KENN151612 KENN192004 KENN171803; MRC HIU Core MCUU00016/14 12009/14 MR/S035850/1 MCPC19059; NIH U192U19AI082630 R24DK106766; NIHR; Rosetrees R35579/AA002/M85-F2; Royal Society RGF\EA\201074 UF150238; UKDHSC PITCH UK-COG; UKRI MR/S005471/1; Wellcome 106130/Z/14/Z 109965MA 107212/A/15/Z 201488/Z/16/Z 203141/Z/16/Z 204826/Z/16/Z 204290/Z/16/Z 204969/Z/16/Z 205228/Z/16/Z 206194 4-SRA-2017-473-A-A 211276/B/18/Z 215097/Z/18/Z 220171/Z/20/Z. Patient recruitment and cohorts (A.J.M. M. Ainsworth, A.A. C.V.A.-C. J.K.B. B.A. A.B. S. Beer, T.B. A. Brent, A. Brown, C.P.C. N.D. J. Dequaire, S.J.D. A.E. R. Fairhead, S. Fassih, J.F. M.F.M. T.F. A. Fries, V.G.S. D.G. C. Hinds, C. Hird, P.H. K. Jeffery, D.K. P. Klenerman, J.C.K. A.K. T.L. J.M. P.C.M. S. McKechnie, D. O'Donnell, A.N. I. Pavord, E.P. T.R. M.R. M.G.S. D. Skelly, A. Sobrinodiaz, L. Stafford, A. Taylor, H.T. L.T. H.U. P.W. R.K.Y. J.Y.), sample processing and extraction (A.J.M. A.A. C.A. A. Beveridge, S. Bibi. T.B. L.B. A. Brown, D.B. S.C. E.A.C. F.C. C.D. T.D. H.D. S. Felle, L.G. A.G. J. Hill, E.J. J.C.K. A.K. A. Lee, A. Linder, L.L. M. Lopopolo. S. Marinou, A.M. Y.P. A.J.P. L.S.-R. C.S.R. C.S.K. G. Scozzafava, H.S. L. Stockdale, M. Strickland, A. Trebes, M.V. L. Witty, K.W. Z.Y. J.Y.), clinical phenotyping (A.J.M. J.K.B. E.B. T.B. C.A.D. L.G. L.-P.H. J.C.K. A.K. L.J. T.P.Q. F.R. S.N.S. M.G.S. A.S.D. L.T. J.Y.), mass and flow cytometry (G.N. M. Salio, C.M. I.U. D.J.A. Y.-X.Z. Z.A. L.D. R. Etherington, J.C.K. P. Kurupati, A.K. M.M. G.O. I. Park, M.P.P. E.R. D.T. E.v.G. L. Wang), whole blood total RNA-seq (A.J.M. M. Attar, K.L.B. E.E.D. J. Docker, C.G. C.H. J.C.K. A.K. A. Linder, D. O'Connor, S.R. J.W.), 10X CITE-seq and repertoire (S.N.S. C.A.D. L.J. J.C.K. R.B.-R. B.F. D.A. M. Attar, P.B. A.P.C. F.C. T.D. R. Ferreira, L.C.G. M.G.V. A.J.-B. A.J. K. Jansen, P. Klenerman, P.K.S. A.K. A. Linder, A.M. A.J.M. R.M. G.N. I.N. L.O. Y.P. F. Penkava, B.P. E.R. S.R. J.-B.R. C.R.-G. H.S. B.S. C.T. S. Thongjuea, O.T. F.A.T. A.V. G.W. R.W. H.Y.Y. Y.-X.Z.), ATAC-seq (T.S.-S. I.C.F. M. Lukoseviciute, M. Attar, S.R. J.C.K. A.K. A. Linder, H.S. M.W.), genetics (L.J. A.C. C.A.D. D.D. C.E. B.F. J. Hughes, J.C.K. A.J.M. Y.M. I.N. R.S. S.N.S. P.Z.), proteomics (mass spectrometry) (R. Fischer, A.S.D. G.B. P.C. S.D. R. Heilig, S.H. J.C.K. Y.M. D.P.O. I.V.) (Luminex) (L.X. W.C. Y.-L.C. D.A.D. P. Klenerman, J.L. C.M. G.O. I. Pavord, I.U.), data integration (J.C.K. M.A.A. R.B.-R. K.L.B. H.B. M.C. F.C. C.A.D. A. Forrow, R. Fischer, T.G. H.A.H. L.-P.H. R. Hoekzema, J. Hughes, M.A.J.-W. L.J. S. McGowan, A.J.M. Y.M. G.N. E.R. F.R. R.S.P. A.S.D. S.N.S. M. Sergeant, A. Seigal, D. Sims, O.S. S. Taylor, A. Tomic, J.W.), data management (B.M. J.B. A.P.C. R. Esnouf, H.F. H.H. L.J. J.C.K. G.K. P. Klenerman, V.K. A.J.M. F. Powrie, S.N.S. D. Sims, J.A.T. D.W.), report and manuscript writing (J.C.K. R.B.-R. K.L.B. F.C. C.A.D. A.S.D. B.F. H.F. R. Fischer, L.C.G. H.A.H. C. Hinds, L.J. A.K. P. Klenerman, A.J.M. B.M. Y.M. G.N. F.R. C.R.-G. A. Seigal, S.N.S. M. Sergeant, T.S-S. B.S. J.A.T. F.A.T. A. Tomic, S. Taylor, J.W. L.X.), steering committee (R.C. F. Powrie, J.C.K. P. Klenerman, A.J.M. H.McS. G.O. A.J.P. G. Screaton, J.A.T.), leadership and oversight (J.C.K. R.B.-R. C.A.D. B.F. R. Fischer, L.J. P. Klenerman, B.M. A.J.M. G.N. S.N.S. T.S.-S. J.A.T. L.X.). Further details and CRediT taxonomy in Data S1. R.B.-R. (co-founder and consultant Alchemab Therapeutics Ltd), R.C. (founder MIROBio), J. Hughes (director and shareholder Nucleome Therapeutics), G.S. (GSK Vaccines SAB), J.A.T. (GSK Human Genetics SAB). Other authors declare no competing interests.

Funding Information:
Research supported by the University of Oxford COVID-19 Research Response Fund and NIHR Oxford Biomedical Research Centre. Work of contributing authors supported by grants ( Data S1 ) including BHF RG/13/9/303269 FS/18/63/34184 ; CAMS IFMS 2018-I2M-2-002 ; CRUK C130623/A249471 ; EPSRC EP/R018472/1 EP/R005125/1 EP/T001968/1 ; Emerson Collective ; Gilead ; Huo Family Foundation ; Kennedy Trust for Rheumatology Research KENN151612 KENN192004 KENN171803 ; MRC HIU Core MCUU00016/14 12009/14 MR/S035850/1 MCPC19059 ; NIH U192U19AI082630 R24DK106766 ; NIHR ; Rosetrees R35579/AA002/M85-F2 ; Royal Society RGF\EA\201074 UF150238 ; UKDHSC PITCH UK-COG ; UKRI MR/S005471/1 ; Wellcome 106130/Z/14/Z 109965MA 107212/A/15/Z 201488/Z/16/Z 203141/Z/16/Z 204826/Z/16/Z 204290/Z/16/Z 204969/Z/16/Z 205228/Z/16/Z 206194 4-SRA-2017-473-A-A 211276/B/18/Z 215097/Z/18/Z 220171/Z/20/Z .

Publisher Copyright:
© 2022 The Author

Keywords

  • COVID-19
  • SARS-CoV-2
  • blood
  • coronavirus
  • epigenetics
  • immune
  • multi-omics
  • personalized medicine
  • proteomics
  • transcriptomics

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