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In this study, we identified an atypical monocyte subpopulation expressing CD56 molecules that showed a low level of HLA-DR and high level of l-selectin. They released higher amounts of TNF-\u03b1 and IL-6 and expressed genes associated with an excessive inflammatory process. Remarkably, the frequency of CD56+ monocytes inversely correlated with that of CD16+ monocytes and a high CD56+\/CD16+monocyte ratio was associated with both disease severity and mortality, as well as with serum concentration of type I IFN, a factor able to induce the appearance of CD56+ monocytes. In conclusion, severe COVID-19 is characterized by the abundance of hyperinflammatory CD56+ monocytes, which could represent a novel marker with prognostic significance and, possibly, a therapeutic target for controlling the inflammatory process occurring during COVID-19.<\/jats:p>","DOI":"10.4049\/jimmunol.2200021","type":"journal-article","created":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T04:54:32Z","timestamp":1672721672000},"page":"655-659","source":"Crossref","is-referenced-by-count":16,"title":["Cutting Edge: Hyperinflammatory Monocytes Expressing CD56 Abound in Severe COVID-19 Patients"],"prefix":"10.1093","volume":"209","author":[{"given":"Stefania","family":"Campana","sequence":"first","affiliation":[{"name":"Laboratory of Immunology and Biotherapy, Department of Human Pathology, University of Messina , Messina,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"De Pasquale","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Biotherapy, Department of Human Pathology, University of Messina , Messina,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Sidoti Migliore","sequence":"additional","affiliation":[{"name":"Immunology Unit, Department of Experimental Medicine, University of Genoa , Genoa,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetana","family":"Pezzino","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Biotherapy, Department of Human Pathology, University of Messina , Messina,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Cavaliere","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Biotherapy, Department of Human Pathology, University of Messina , Messina,","place":["Italy"]},{"name":"Clinical Pathology Unit, University Hospital Policlinico \u201cG. 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Martino,\u201d Messina ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9807-327X","authenticated-orcid":false,"given":"Gaetano","family":"Caramori","sequence":"additional","affiliation":[{"name":"Department BIOMORF, University of Messina , Messina,","place":["Italy"]},{"name":"Pulmonology Unit, University Hospital Policlinico \u201cG. Martino,\u201d Messina ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"David","sequence":"additional","affiliation":[{"name":"Department of Human Pathology, University of Messina , Messina,","place":["Italy"]},{"name":"Intensive Care Unit, University Hospital Policlinico \u201cG. 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