Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients

Ulas, T.; Seep, L.; Schulte-Schrepping, J.; De Domenico, E.; Mengiste, S.; Theis, H.; Kraut, M.; Becker, M.; Gierlich, J.; Lenkeit, L.; Drews, A.; van Uelft, M.; Dahm, K.; Agrawal, S.; Gemuend, I. D.; Horne, A.; Holsten, L.; Herbert, M.; Kroeger, C.; Kapellos, T. S.; Pecht, T.; Knoll, R.; Bassler, K.; Reusch, N.; Bonaguro, L.; Nuesch-Germano, M.; Oestreich, M.; Aschenbrenner, A. C.; Schultze, J. L.; Kox, M.; Bruse, N.; Pickkers, P.; Gerretsen, J.; Netea, M. G.; van de Veerdonk, F.; Nattermann, J.; Kraemer, B.; Raabe, J.; ToVinh, M.; Hoffmeister, C.; Rieke, G. J.; Keitel, V.; Breteler, M. M.

The SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, respiratory failure, and death. Reports on a dysregulated immune system in the severe cases calls for a better characterization and understanding of the changes in the immune system. Here, we profiled whole blood transcriptomes of 39 COVID-19 patients and 10 control donors enabling a data-driven stratification based on molecular phenotype. Neutrophil activation-associated signatures were prominently enriched in severe patient groups, which was corroborated in whole blood transcriptomes from an independent second cohort of 30 as well as in granulocyte samples from a third cohort of 11 COVID-19 patients. Comparison of COVID-19 blood transcriptomes with those of a collection of over 2,600 samples derived from 11 different viral infections, inflammatory diseases and independent control samples revealed highly specific transcriptome signatures for COVID-19. Further, stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host.