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Background: COVID-19 has put a huge strain on the healthcare systems worldwide, requiring unprecedented intensive care resources. There is still an unmet clinical need for easily available biomarkers capable of predicting the risk for severe disease. The main goal of this prospective multicenter study was to identify biomarkers that could predict ICU admission and in-hospital mortality., Methods: We prospectively recruited COVID-19 PCR positive patients in two hospitals, in Belgium and Italy. Blood samples were collected at hospital admission and 20 potential biomarkers were measured with the Luminex technology. Logistic regression models were performed to identify the biomarkers that, alone or together, were associated with patient disease severity., Results: Our study demonstrates that elevated levels of circulating inflammatory cytokines were associated with disease severity in COVID-19 hospitalized patients. CXCL10, IL-4, IL-6 and MCP-1 values were predictive of ICU admission. Elevated levels of IL-6 and MCP-1 were also associated with in hospital death in COVID-19 hospitalized patients., Conclusion: Altogether, elevated and correlated inflammatory cytokines in the blood of COVID-19 patients at hospital admission are predictive of disease severity and suggest a dysregulated inflammation induced by SARS-CoV-2 infection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. JS, RPR, PS and EP are employees of TopMD with JS, PS and FS also being directors and shareholders. JG reports personal fees for advisory board, work and lectures from Boehringer Ingelheim, Janssen, SMB, GSK, Roche, AstraZeneca, Aquilon, Volition, Oncoradiomics, and Chiesi, non-financial support for meeting attendance from AstraZeneca, Chiesi, MSD, Roche, Boehringer Ingelheim and Janssen. He is in the permanent SAB of Radiomics (Oncoradiomics SA) for the SALMON trial without any specific consultancy fee for this work. He is co-inventor of one issued patent on radiomics licensed to Radiomics (Oncoradiomics SA). He confirms that none of the above entities or funding was involved in the preparation of this work., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The blood contains high concentrations of circulating extracellular vesicles (EVs), and their levels and contents are altered in several disease states, including cardiovascular disease. However, the function of circulating EVs, especially the microRNAs (miRNAs) that they contain, are poorly understood. We sought to determine the effect of secreted vesicles produced by quiescent endothelial cells (ECs) on monocyte inflammatory responses and to assess whether transfer of microRNAs occurs between these cells. We observed that monocytic cells cocultured (but not in contact) with ECs were refractory to inflammatory activation. Further characterization revealed that endothelium-derived EVs (EC-EVs) suppressed monocyte activation by enhancing immunomodulatory responses and diminishing proinflammatory responses. EVs isolated from mouse plasma also suppressed monocyte activation. Importantly, injection of EC-EVs in vivo repressed monocyte/macrophage activation, confirming our in vitro findings. We found that several antiinflammatory microRNAs were elevated in EC-EV-treated monocytes. In particular, miR-10a was transferred to monocytic cells from EC-EVs and could repress inflammatory signaling through the targeting of several components of the NF-κB pathway, including IRAK4. Our findings reveal that ECs secrete EVs that can modulate monocyte activation and suggest that altered EV secretion and/or microRNA content may affect vascular inflammation in the setting of cardiovascular disease., (© 2015 by The American Society of Hematology.)