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

Treatment 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. The complete raw and processed CITE-seq datasets are available at the European Genome-phenome Archive (EGA) and Zenodo respectively. Here a more limited version of the gene expression data is presented for the purpose of online visualisation and exploration of the dataset. Please note that features have been automatically filtered for compatibility with the Cellxgene Data Portal (ADT features have been removed). For further analysis it is recommended to use the unfiltered datasets from the EGA or Zenodo (where processed datasets are also available in anndata format).