Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature by monocytes in COVID-19
Allison K. Maher, Katie L. Burnham, Emma Jones, Michelle MH Tan, Rocel C. Saputil, Laury Baillon, Claudia Selck, Nicolas Giang, Rafael J. Argüello, Clio Pillay, Emma Thorley, Charlotte‐Eve Short, Rachael Quinlan, William Barclay, Nichola Cooper, Graham P. Taylor, Emma E. Davenport, Margarita Dominguez‐Villar
Abstract
monocytes in patients with mild and moderate COVID-19 during the acute phase of infection and in healthy individuals. Monocytes from COVID-19 patients display altered expression of cell surface receptors and a dysfunctional metabolic profile that distinguish them from healthy monocytes. Secondary pathogen sensing ex vivo leads to defects in pro-inflammatory cytokine and type-I IFN production in moderate COVID-19 cases, together with defects in glycolysis. COVID-19 monocytes switch their gene expression profile from canonical innate immune to pro-thrombotic signatures and are functionally pro-thrombotic, both at baseline and following ex vivo stimulation with SARS-CoV-2. Transcriptionally, COVID-19 monocytes are characterized by enrichment of pathways involved in hemostasis, immunothrombosis, platelet aggregation and other accessory pathways to platelet activation and clot formation. These results identify a potential mechanism by which monocyte dysfunction may contribute to COVID-19 pathology.