Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity

• DOI: 10.1038/s41467-021-24360-w
• Publication Date: 2021-07-05T10:04:04Z
• Authors: L. Vanderbeke; P. Van Mol; Y. Van Herck; F. De Smet; S. Humblet-Baron; K. Martinod; A. Antoranz; I. Arijs; B. Boeckx; F. M. Bosisio; M. Casaer; D. Dauwe; W. De Wever; C. Dooms; E. Dreesen; A. Emmaneel; J. Filtjens; M. Gouwy; J. Gunst; G. Hermans; S. Jansen; K. Lagrou; A. Liston; N. Lorent; P. Meersseman; T. Mercier; J. Neyts; J. Odent; D. Panovska; P. A. Penttila; E. Pollet; P. Proost; J. Qian; K. Quintelier; J. Raes; S. Rex; Y. Saeys; J. Sprooten; S. Tejpar; D. Testelmans; K. Thevissen; T. Van Buyten; J. Vandenhaute; S. Van Gassen; L. C. Velásquez P...; R. Vos; B. Weynand; A. Wilmer; J. Yserbyt; A. D. Garg; P. Matthys; C. Wouters; D. Lambrechts; E. Wauters; J. Wauters
• Keywords: Cytokine Storm; 2019-20 coronavirus outbreak; Monocyte

Epidemiological and clinical reports indicate that SARS-CoV-2 virulence hinges upon the triggering of an aberrant host immune response, more so than on direct virus-induced cellular damage. To elucidate immunopathology underlying COVID-19 severity, we perform cytokine multiplex profiling in patients. We show hypercytokinemia differs from interferon-gamma-driven storm macrophage activation syndrome, is pronounced critical versus mild-moderate COVID-19. Systems modelling levels paired with deep-immune shows classical monocytes drive this hyper-inflammatory phenotype a reduction T-lymphocytes correlates disease CD8+ cells being disproportionately affected. Antigen presenting machinery expression also reduced disease. Furthermore, report neutrophils contribute to severity local tissue damage by amplification formation neutrophil extracellular traps. Together our findings suggest myeloid-driven immunopathology, which hyperactivated ineffective adaptive system act as mediators severity.