{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T21:38:19Z","timestamp":1783114699570,"version":"3.54.6"},"reference-count":34,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T00:00:00Z","timestamp":1715904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union-NextGeneration EU","award":["341\/2022"],"award-info":[{"award-number":["341\/2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Patients with COVID-19 have coagulation and platelet disorders, with platelet alterations and thrombocytopenia representing negative prognostic parameters associated with severe forms of the disease and increased lethality. Methods: The aim of this study was to study the expression of platelet glycoprotein IIIa (CD61), playing a critical role in platelet aggregation, together with TRL-2 as a marker of innate immune activation. Results: A total of 25 patients were investigated, with the majority (24\/25, 96%) having co-morbidities and dying from a fatal form of SARS-CoV-2(+) infection (COVID-19+), with 13 men and 12 females ranging in age from 45 to 80 years. When compared to a control group of SARS-CoV-2 (\u2212) negative lungs (COVID-19\u2212), TLR-2 expression was up-regulated in a subset of patients with deadly COVID-19 fatal lung illness. The proportion of Spike-1 (+) patients found by PCR and ISH correlates to the proportion of Spike-S1-positive cases as detected by digital pathology examination. Furthermore, CD61 expression was considerably higher in the lungs of deceased patients. In conclusion, we demonstrate that innate immune prolonged hyperactivation is related to platelet\/megakaryocyte over-expression in the lung. Conclusions: Microthrombosis in deadly COVID-19+ lung disease is associated with an increase in the number of CD61+ platelets and megakaryocytes in the pulmonary interstitium, as well as their functional activation; this phenomenon is associated with increased expression of innate immunity TLR2+ cells, which binds the SARS-CoV-2 E protein, and significantly with the persistence of the Spike-S1 viral sequence.<\/jats:p>","DOI":"10.3390\/cells13100854","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T04:26:29Z","timestamp":1715919989000},"page":"854","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Role of TLR-2 in Lethal COVID-19 Disease Involving Medullary and Resident Lung Megakaryocyte Up-Regulation in the Microthrombosis Mechanism"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4198-407X","authenticated-orcid":false,"given":"Giuseppe","family":"Pannone","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, Viale L.Pinto 1, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Carmela","family":"Pedicillo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, Viale L.Pinto 1, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4955-2039","authenticated-orcid":false,"given":"Ilenia Sara","family":"De Stefano","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, Viale L.Pinto 1, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Angelillis","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, Viale L.Pinto 1, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Barile","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Foggia, Viale L.Pinto 1, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Pannone","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universit\u00e0 della Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2362-5022","authenticated-orcid":false,"given":"Giuliana","family":"Villani","sequence":"additional","affiliation":[{"name":"Policlinico Riuniti, University-Hospital, Viale L.Pinto 1, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7368-258X","authenticated-orcid":false,"given":"Francesco","family":"Miele","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Campania \u201cL Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Municin\u00f2","sequence":"additional","affiliation":[{"name":"Forensic Medicine Unit, \u201cS. Giuliano\u201d Hospital, Via Giambattista Basile, 80014 Giugliano in Campania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Ronchi","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania \u201cL Vanvitelli\u201d, Via Luciano Armanni, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6424-7841","authenticated-orcid":false,"given":"Gaetano","family":"Serviddio","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Foggia, Viale L.Pinto 1, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Zito Marino","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania \u201cL Vanvitelli\u201d, Via Luciano Armanni, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato","family":"Franco","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania \u201cL Vanvitelli\u201d, Via Luciano Armanni, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6927-403X","authenticated-orcid":false,"given":"Tommaso","family":"Colangelo","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Foggia, Viale L.Pinto 1, 71122 Foggia, Italy"},{"name":"Cancer Cell Signalling Unit, Institute for Stem-Cell Biology, Regenerative Medicine and Innovative Therapies (ISBReMIT), IRCCS Fondazione Casa Sollievo della Sofferenza, Viale Cappuccini sc.c., San Giovanni Rotondo, 71013 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanna","family":"Zamparese","sequence":"additional","affiliation":[{"name":"Legal Medicine Unit, Ascoli Piceno Hospital C-G. 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