{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:55:09Z","timestamp":1790268909251,"version":"4.1.0"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>SARS-CoV-2 infections cause COVID-19 and are associated with inflammation, coagulopathy, and high incidence of thrombosis. Myeloid cells help coordinate the initial immune response in COVID-19. Although we appreciate that myeloid cells lie at the nexus of inflammation and thrombosis, the mechanisms that unite the two in COVID-19 remain largely unknown.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>In this study, we used systems biology approaches including proteomics, transcriptomics, and mass cytometry to define the circulating proteome and circulating immune cell phenotypes in subjects with COVID-19.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>In a cohort of subjects with COVID-19 (n=35), circulating markers of inflammation (CCL23 [C-C motif chemokine ligand 23] and IL [interleukin]-6) and vascular dysfunction (ACE2 [angiotensin-converting enzyme 2] and TF [tissue factor]) were elevated in subjects with severe compared with mild COVID-19. Additionally, although the total white blood cell counts were similar between COVID-19 groups, CD14+ (cluster of differentiation) monocytes from subjects with severe COVID-19 expressed more TF. At baseline, transcriptomics demonstrated increased IL-6, CCL3, ACOD1 (aconitate decarboxylase 1), C5AR1 (complement component 5a receptor), C5AR2, and TF in subjects with severe COVID-19 compared with controls. Using stress transcriptomics, we found that circulating immune cells from subjects with severe COVID-19 had evidence of profound immune paralysis with greatly reduced transcriptional activation and release of inflammatory markers in response to TLR (Toll-like receptor) activation. Finally, sera from subjects with severe (but not mild) COVID-19 activated human monocytes and induced TF expression.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>Taken together, these observations further elucidate the pathological mechanisms that underlie immune dysfunction and coagulation abnormalities in COVID-19, contributing to our growing understanding of SARS-CoV-2 infections that could also be leveraged to develop novel diagnostic and therapeutic strategies.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.122.318721","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T09:00:32Z","timestamp":1711011632000},"page":"1124-1134","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Monocyte-Mediated Thrombosis Linked to Circulating Tissue Factor and Immune Paralysis in COVID-19"],"prefix":"10.1161","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3772-8818","authenticated-orcid":true,"given":"Sascha N.","family":"Goonewardena","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor (S.N.G., A.M.T., O.G.G., D.D., P.K.B., S.S.H., D.J.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7814-9145","authenticated-orcid":true,"given":"Qinzhong","family":"Chen","sequence":"additional","affiliation":[{"name":"Metabolism and Lipids Unit, Cardiovascular Institute, Marie-Josee and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York, NY (Q.C., R.S.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0096-741X","authenticated-orcid":true,"given":"Ashley M.","family":"Tate","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor (S.N.G., A.M.T., O.G.G., D.D., P.K.B., S.S.H., D.J.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9330-1798","authenticated-orcid":true,"given":"Olga G.","family":"Grushko","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor (S.N.G., A.M.T., O.G.G., D.D., P.K.B., S.S.H., D.J.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2735-6803","authenticated-orcid":true,"given":"Dilna","family":"Damodaran","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor (S.N.G., A.M.T., O.G.G., D.D., P.K.B., S.S.H., D.J.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9677-3010","authenticated-orcid":true,"given":"Pennelope K.","family":"Blakely","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor (S.N.G., A.M.T., O.G.G., D.D., P.K.B., S.S.H., D.J.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0180-349X","authenticated-orcid":true,"given":"Salim S.","family":"Hayek","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor (S.N.G., A.M.T., O.G.G., D.D., P.K.B., S.S.H., D.J.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Pinsky","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor (S.N.G., A.M.T., O.G.G., D.D., P.K.B., S.S.H., D.J.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5599-0633","authenticated-orcid":true,"given":"Robert S.","family":"Rosenson","sequence":"additional","affiliation":[{"name":"Metabolism and Lipids Unit, Cardiovascular Institute, Marie-Josee and Henry R. 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