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

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.

Publication History

Received: 25 September 2024

Accepted: 19 March 2025

Article published online:
30 April 2025

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