A multi-disciplinary, cross-divisional collaborative team led by the University of Oxford has published a study defining hallmarks of COVID-19 disease severity. The team, led by Professor Julian Knight at the Wellcome Centre for Human Genetics, included over 200 researchers across 10 Medical Sciences Division and Mathematical, Physical and Life Sciences Division departments, clinicians and nurses at Oxford University Hospital NHS Foundation Trust and collaborators across the country. The team performed multiple ‘omics analyses on the blood of patients with varying COVID-19 severity and compared with severe influenza patients, sepsis patients and healthy volunteers.
Hallmarks of illness severity involved cells, their inflammatory mediators and networks as potential 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 p38MAPK/AP- 1 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. The systems-based integrative approach and blood atlas will inform future drug development, clinical trial design and personalised medicine approaches for COVID-19.