Petito Eleonora, Guglielmini Giuseppe, De Robertis Edoardo, Becattini Cecilia, Franco Laura, Falcinelli Emanuela, Conti Chiara, Gori Fabio, Vaudo Gaetano, Cerotto Vittorio, Paliani Ugo, Mezzasoma Letizia, Camilloni Barbara, Gresele Paolo
Division of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy.
Division of Anaesthesia, Analgesia, and Intensive Care, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
Thromb Haemost. 2025 Jul;125(7):660-672. doi: 10.1055/a-2562-4516. Epub 2025 Apr 30.
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.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.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.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.
氧化应激与新型冠状病毒肺炎（COVID-19）相关的血栓形成并发症有关。尚无研究探讨血小板产生一氧化氮（NO）和活性氧（ROS）的情况。事实上，活化的血小板会产生NO和ROS，进而调节血小板功能。本研究的目的是测量COVID-19患者血小板中NO和ROS的产生情况，评估它们是否与疾病预后相关，并阐明COVID-19中血小板NO/ROS失衡的机制。纳入了住院的轻症和重症COVID-19患者、年龄和性别匹配的健康对照者，以及因非COVID-19原因入住重症监护病房的患者。通过流式细胞术评估血小板NO和ROS的产生情况。使用脂质过氧化和氧自由基吸收能力（ORAC）测定法评估COVID-19血浆的氧化和抗氧化能力。通过流式细胞术研究COVID-19血浆对血小板NO产生的影响以及抗氧化剂对其的影响。COVID-19患者的血小板表现出NO/ROS平衡改变，NO产生缺陷且ROS产生增加。在住院期间发生血栓事件的患者中，血小板NO产生显著降低。与健康对照者相比，COVID-19患者的血浆脂质过氧化显著增加，抗氧化能力降低。同样，COVID-19患者的血浆损害了健康对照者血小板的NO产生，而抗氧化剂羟基-TEMPO可使其恢复。我们的研究结果表明，COVID-19中血小板NO/ROS产生失衡在严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的血栓形成并发症中起作用。恢复血小板NO产生可能是预防COVID-19患者血栓事件的治疗靶点。
