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Thromb Haemost
DOI: 10.1055/a-2562-4516
Cellular Hemostasis and Platelets

Platelets from COVID-19 Patients Show an Altered Nitric Oxide/Reactive Oxygen Species Production Balance

Eleonora Petito
1   Division of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy
,
Giuseppe Guglielmini
1   Division of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy
,
Edoardo De Robertis
2   Division of Anaesthesia, Analgesia, and Intensive Care, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
,
Cecilia Becattini
1   Division of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy
,
Laura Franco
1   Division of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy
,
Emanuela Falcinelli
1   Division of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy
,
Chiara Conti
1   Division of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy
,
Fabio Gori
3   Section of Anesthesia, Intensive Care, and Pain Medicine, Azienda Ospedaliera-Universitaria Santa Maria della Misericordia, Perugia, Italy
,
Gaetano Vaudo
4   Unit of Internal Medicine, Terni University Hospital, Terni, Italy
,
Vittorio Cerotto
5   Section of Anesthesia, Intensive Care and Pain Medicine, Department of Emergency and Urgency, Città di Castello Hospital, Città di Castello, Italy
,
Ugo Paliani
6   Division of Internal Medicine, ASL 1 Umbria, Città di Castello, Italy
,
Letizia Mezzasoma
7   Department of Medicine and Surgery, Section of Biosciences and Medical Embryology, University of Perugia, Perugia, Italy
,
Barbara Camilloni
8   Department of Medicine and Surgery, Microbiology and Clinical Microbiology, University of Perugia, Perugia, Italy
,
Paolo Gresele 
1   Division of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy
,
COVIR study investigators › Author Affiliations Funding This work was supported in part by a grant from Fondazione Cassa di Risparmio di Perugia, project 19663 (2020.0508), and in part by a fellowship from Fondazione Umberto Veronesi to Eleonora Petito.
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Abstract

Background

Oxidative stress has been associated with COVID-19-related thrombotic complications. No investigations have explored nitric oxide (NO) and radical oxygen species (ROS) production by platelets. Indeed, activated platelets generate both NO and ROS which in turn regulate platelet function. The aim of the present study was to measure platelet NO and ROS production in COVID-19 patients, to assess whether they correlate with disease outcome and to clarify the mechanisms of platelet NO/ROS imbalance in COVID-19.

Material and Methods

Hospitalized mild and severe COVID-19 patients, age- and sex-matched healthy controls, and patients hospitalized in intensive care units for reasons different from COVID-19 were enrolled. Platelet NO and ROS production was assessed by flow cytometry. The oxidant and antioxidant capacity of COVID-19 plasma was assessed using lipid peroxidation and ORAC assays. The effect of COVID-19 plasma on platelet NO production and the impact of antioxidants on it were studied by flow cytometry.

Results

Platelets from COVID-19 patients displayed an altered NO/ROS balance, with defective NO and increased ROS production. Platelet NO production was significantly lower in patients who developed thrombotic events during hospitalization. COVID-19 patients showed significantly increased plasma lipid peroxidation and reduced antioxidant capacity compared with healthy controls. Concordantly, plasma from COVID-19 patients impaired NO production by healthy control species platelets, which was restored by the antioxidant agent Hydroxy-TEMPO.

Conclusion

Our findings suggest that the unbalanced platelet NO/ROS production in COVID-19 plays a role in the thrombotic complications of SARS-CoV-2 infection. The restoration of platelet NO production may represent a therapeutic target for the prevention of thrombotic events in COVID-19 patients.

Keywords

COVID-19 - nitric oxide - platelets - reactive oxygen species - thrombosis

Authors' Contribution

P.G. designed and supervised the study; G.G., E.P., and E.F. performed the experiments; E.P. and P. Gresele analyzed and interpreted data; B. Camilloni provided data on SARS-CoV-2 variants; L. Mezzasoma contributed to inflammasome investigation; E. Petito and P. Gresele wrote the manuscript; E. De Robertis, C. Becattini, L. Franco, F. Gori, G. Vaudo, V. Cerotto, and U. Paliani enrolled patients and provided clinical data; COVIR-Study Collaborators contributed to patient enrollment and study management.


* The members of the COVIR study investigators are: Mezzasoma A. M., Saccarelli L., Cristallini S., D'Abbondanza M., Lapenna M.


Supplementary Material



Publication History

Received: 25 September 2024

Accepted: 19 March 2025

Article published online:
30 April 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

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