Sasso Etianne Martini, Eaton-Fitch Natalie, Smith Peter, Muraki Katsuhiko, Marshall-Gradisnik Sonya
The National Centre for Neuroimmunology and Emerging Diseases, Griffith University, Gold Coast, QLD, Australia.
Consortium Health International for Myalgic Encephalomyelitis, National Centre for Neuroimmunology and Emerging Diseases, Griffith University, Gold Coast, QLD, Australia.
Front Mol Biosci. 2025 May 19;12:1582967. doi: 10.3389/fmolb.2025.1582967. eCollection 2025.
Long COVID is a multisystemic condition that includes neurocognitive, immunological, gastrointestinal, and cardiovascular manifestations, independent of the severity or duration of the acute SARS-CoV-2 infection. Dysfunctional Transient Receptor Potential Melastatin 3 (TRPM3) ion channels are associated with the pathophysiology of long COVID due to reduced calcium (Ca) influx, negatively impacting cellular processes in diverse systems. Accumulating evidence suggests the potential therapeutic benefits of low-dose naltrexone (LDN) for people suffering from long COVID. Our study aimed to investigate the efficacy of LDN in restoring TRPM3 ion channel function in natural killer (NK) cells from long COVID patients.
NK cells were isolated from nine individuals with long COVID, nine healthy controls, and nine individuals with long COVID who were administered LDN (3-4.5 mg/day). Electrophysiological experiments were conducted to assess TRPM3 ion channel functions modulated by pregnenolone sulfate (PregS) and ononetin.
The findings from this current research are the first to demonstrate that long COVID patients treated with LDN have restored TRPM3 ion channel function and validate previous reports of TRPM3 ion channel dysfunction in NK cells from individuals with long COVID not on treatment. There was no significant difference in TRPM3 currents between long COVID patients treated with LDN and healthy controls (HC), in either PregS-induced current amplitude (p > 0.9999) or resistance to ononetin (p > 0.9999).
Overall, our findings support LDN as a potentially beneficial treatment for long COVID patients by restoring TRPM3 ion channel function and reestablishing adequate Ca influx necessary for homeostatic cellular processes.
新冠后遗症是一种多系统病症，包括神经认知、免疫、胃肠和心血管方面的表现，与急性SARS-CoV-2感染的严重程度或持续时间无关。功能失调的瞬时受体电位褪黑素3（TRPM3）离子通道与新冠后遗症的病理生理学相关，因为钙（Ca）内流减少，对不同系统的细胞过程产生负面影响。越来越多的证据表明，低剂量纳曲酮（LDN）对新冠后遗症患者可能具有治疗益处。我们的研究旨在调查LDN对恢复新冠后遗症患者自然杀伤（NK）细胞中TRPM3离子通道功能的疗效。
从9名新冠后遗症患者、9名健康对照者以及9名接受LDN治疗（3 - 4.5毫克/天）的新冠后遗症患者中分离出NK细胞。进行电生理实验以评估由硫酸孕烯醇酮（PregS）和芒柄花黄素调节的TRPM3离子通道功能。
本研究的结果首次表明，接受LDN治疗的新冠后遗症患者的TRPM3离子通道功能得以恢复，并验证了先前关于未接受治疗的新冠后遗症患者NK细胞中TRPM3离子通道功能障碍的报道。在接受LDN治疗的新冠后遗症患者与健康对照者（HC）之间，TRPM3电流在PregS诱导的电流幅度（p > 0.9999）或对芒柄花黄素的抗性（p > 0.9999）方面均无显著差异。
总体而言，我们的研究结果支持LDN作为一种对新冠后遗症患者可能有益的治疗方法，通过恢复TRPM3离子通道功能并重新建立细胞稳态过程所需的充足Ca内流。
