The Role of TLR-2 in Lethal COVID-19 Disease Involving Medullary and Resident Megakaryocites Up-Regulation in the Microthrombosis Mechanism

Giuseppe Prof Pannone; Maria Carmela Pedicillo; Ilenia Sara De Stefano; Raffaele Barile; Mario Meccariello; Alessio Agostinone; Chiara Pannone; Giuliana Villani; CRISTINA PIZZULLI; Francesco Miele; Maria Antonietta Ramunno; Maurizio Municinò; Gaetano Serviddio; Andrea Ronchi; Federica Zito Marino; Renato Franco; Tommaso Colangelo; Rosanna Zamparese

doi:10.20944/preprints202311.0508.v1

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preprints.org > medicine and pharmacology > pathology and pathobiology > doi: 10.20944/preprints202311.0508.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Role of TLR-2 in Lethal COVID-19 Disease Involving Medullary and Resident Megakaryocites Up-Regulation in the Microthrombosis Mechanism

Giuseppe Prof Pannone

^* ,

Maria Carmela Pedicillo

Ilenia Sara De Stefano

Maria Antonietta Ramunno

Version 1 : Received: 6 November 2023 / Approved: 8 November 2023 / Online: 8 November 2023 (16:01:16 CET)

How to cite: Pannone, G.P.; Pedicillo, M.C.; De Stefano, I.S.; Barile, R.; Meccariello, M.; Agostinone, A.; Pannone, C.; Villani, G.; PIZZULLI, C.; Miele, F.; Ramunno, M.A.; Municinò, M.; Serviddio, G.; Ronchi, A.; Zito Marino, F.; Franco, R.; Colangelo, T.; Zamparese, R. The Role of TLR-2 in Lethal COVID-19 Disease Involving Medullary and Resident Megakaryocites Up-Regulation in the Microthrombosis Mechanism. Preprints 2023, 2023110508. https://doi.org/10.20944/preprints202311.0508.v1 Pannone, G.P.; Pedicillo, M.C.; De Stefano, I.S.; Barile, R.; Meccariello, M.; Agostinone, A.; Pannone, C.; Villani, G.; PIZZULLI, C.; Miele, F.; Ramunno, M.A.; Municinò, M.; Serviddio, G.; Ronchi, A.; Zito Marino, F.; Franco, R.; Colangelo, T.; Zamparese, R. The Role of TLR-2 in Lethal COVID-19 Disease Involving Medullary and Resident Megakaryocites Up-Regulation in the Microthrombosis Mechanism. Preprints 2023, 2023110508. https://doi.org/10.20944/preprints202311.0508.v1

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MDPI and ACS Style

Pannone, G.P.; Pedicillo, M.C.; De Stefano, I.S.; Barile, R.; Meccariello, M.; Agostinone, A.; Pannone, C.; Villani, G.; PIZZULLI, C.; Miele, F.; Ramunno, M.A.; Municinò, M.; Serviddio, G.; Ronchi, A.; Zito Marino, F.; Franco, R.; Colangelo, T.; Zamparese, R. The Role of TLR-2 in Lethal COVID-19 Disease Involving Medullary and Resident Megakaryocites Up-Regulation in the Microthrombosis Mechanism. Preprints 2023, 2023110508. https://doi.org/10.20944/preprints202311.0508.v1

APA Style

Pannone, G.P., Pedicillo, M.C., De Stefano, I.S., Barile, R., Meccariello, M., Agostinone, A., Pannone, C., Villani, G., PIZZULLI, C., Miele, F., Ramunno, M.A., Municinò, M., Serviddio, G., Ronchi, A., Zito Marino, F., Franco, R., Colangelo, T., & Zamparese, R. (2023). The Role of TLR-2 in Lethal COVID-19 Disease Involving Medullary and Resident Megakaryocites Up-Regulation in the Microthrombosis Mechanism. Preprints. https://doi.org/10.20944/preprints202311.0508.v1

Chicago/Turabian Style

Pannone, G.P., Tommaso Colangelo and Rosanna Zamparese. 2023 "The Role of TLR-2 in Lethal COVID-19 Disease Involving Medullary and Resident Megakaryocites Up-Regulation in the Microthrombosis Mechanism" Preprints. https://doi.org/10.20944/preprints202311.0508.v1

Abstract

Patients with COVID-19 have coagulation and platelet disorders, with platelet’s alterations and thrombocytopenia representing negative prognostic parameters, being associated with severe forms of the disease, and increase lethality. Methods: Aim of this study was to study 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 (-) negative lungs (COVID-19 -), 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 dead patients. In conclusion, we demonstrate that innate immune prolonged hyperactivation is related to platelet/megakaryocytes 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.

Keywords

TRLs; TRL-2; SARS-CoV-2; lethal COVID-19; lung disease; ARDS; CD61; micro-thrombosis; megakaryocites

Subject

Medicine and Pharmacology, Pathology and Pathobiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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