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 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.

Automated summary

The study presents a comprehensive blood atlas for patients with varying severity of COVID-19, compared to influenza, sepsis patients, and healthy volunteers. The results identify immune signatures and correlates of host response, including cells, inflammatory mediators, immune repertoire, and metabolic and coagulation features. The study also reveals that persistent immune activation is a specific feature of COVID-19. Plasma proteomic analysis enables sub-phenotyping and prediction of severity and outcome. Integrative analyses show feature groupings linked with severity and specificity compared to influenza and sepsis.