Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity
Year: 2020
Type: preprint
Study design: Observational Study
Abstract: Epidemiological and clinical reports have indicated that the host immune response to SARS-CoV-2, more so than viral factors, determines COVID-19 disease severity. To elucidate the immunopathology underlying COVID-19 severity, cytokine and multiplex immune profiling was performed in mild-moderate and critically-ill COVID-19 patients. Hypercytokinemia in COVID-19 differed from the IFN-γ-driven cytokine storm in macrophage activation syndrome, and was more pronounced in critical versus mild-moderate COVID-19. Systems modelling of cytokine levels followed by deep-immune profiling showed that classical monocytes drive this hyper-inflammatory phenotype and that a reduction in T-lymphocytes correlates with disease severity, with CD8+ cells being disproportionately affected. Expression of antigen presenting machinery was reduced in critical disease, while also neutrophils contributed to disease severity and local tissue damage by amplifying hypercytokinemia and neutrophil extracellular trap formation. We suggest a myeloid-driven immunopathology, in which hyperactivated neutrophils and an ineffective adaptive immune system act as mediators of COVID-19 disease severity.
Authors: Lore Vanderbeke, Pierre Van Mol, Yannick van Herck, Frederik De Smet, Stephanie Humblet-Baron, Kimberly Martinod, Asier Antoranz, Ingrid Arijs, Bram Boeckx, Francesca Bosisio, Michael Casaer, Dieter Dauwe, Walter De Wever, Christophe Dooms, Erwin Dreesen, Annelies Emmaneel, Jessica Filtjens, Mieke Gouwy, Jan Gunst, Greet Hermans, Sander Jansen, Katrien Lagrou, Adrian Liston, Natalie Lorent, Philippe Meersseman, Toine Mercier, Johan Neyts, Julie Odent, Dena Panovska, Pier Andree Penttila, Emily Pollet, Paul Proost, Junbin Qian, Katrien Quintelier, Jeroen Raes, Steffen Rex, Yvan Saeys, Jenny Sprooten, Sabine Tejpar, Dries Testelmans, Karin Thevissen, Tina Van Buyten, Jessica Vandenhaute, Sofie Van Gassen, Leydi Velasquez Pereira, Robin Vos, Birgit Weynand, Alexander Wilmer, Jonas Yserbyt, Abhishek Garg, Patrick Matthys, Carine Wouters, Diether Lambrechts, Els Wauters, Joost Wauters
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G206476922, Antimicrobial dosing in critically ill patients with severe sepsis and septic shock: a novel patient-oriented and covariate driven approach, G2721486572, G4074580793, A single-cell approach to identify biomarkers of efficacy and toxicity for immune checkpoint blockade in non-small cell lung cancer., Mass cytometry by time-of-flight: next-generation flow cytometry for multiplexed single cell analysis, G5290570178, G5918159827, G6386971566, Pharmacometric models for improved therapeutic drug monitoring of ceftriaxone, posaconazole and infliximab, The co-pathogenesis of severe influenza with invasive pulmonary aspergillosis., G7619121530, G968185766
OpenAlex ID: W4245422695