Coronavirus disease 2019 (COVID-19) can lead to severe acute respiratory syndrome, and while most individuals recover within weeks, approximately 30–40% experience persistent symptoms collectively known as Long COVID, post-COVID-19 syndrome, or post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC). These enduring symptoms, including fatigue, respiratory difficulties, body pain, short-term memory loss, concentration issues, and sleep disturbances, can persist for months. According to recent studies, SARS-CoV-2 infection causes prolonged disruptions in mitochondrial function, significantly altering cellular energy metabolism. Our research employed transmission electron microscopy to reveal distinct mitochondrial structural abnormalities in Long COVID patients, notably including significant swelling, disrupted cristae, and an overall irregular morphology, which collectively indicates severe mitochondrial distress. We noted increased levels of superoxide dismutase 1 which signals oxidative stress and elevated autophagy-related 4B cysteine peptidase levels, indicating disruptions in mitophagy. Importantly, our analysis also identified reduced levels of circulating cell-free mitochondrial DNA (ccf-mtDNA) in these patients, serving as a novel biomarker for the condition. These findings underscore the crucial role of persistent mitochondrial dysfunction in the pathogenesis of Long COVID. Further exploration of the cellular and molecular mechanisms underlying post-viral mitochondrial dysfunction is critical, particularly to understand the roles of autoimmune reactions and the reactivation of latent viruses in perpetuating these conditions. This comprehensive understanding could pave the way for targeted therapeutic interventions designed to alleviate the chronic impacts of Long COVID. By utilizing circulating ccf-mtDNA and other novel mitochondrial biomarkers, we can enhance our diagnostic capabilities and improve the management of this complex syndrome.

2019 冠状病毒病 （COVID-19） 可导致严重急性呼吸系统综合症，虽然大多数人在几周内康复，但大约 30-40% 的人会出现持续症状，统称为长期 COVID、COVID-19 后综合征或严重急性呼吸系统综合症冠状病毒 2 （SARS-CoV-2） 感染 （PASC） 的急性后遗症。这些持久的症状，包括疲劳、呼吸困难、身体疼痛、短期记忆丧失、注意力不集中和睡眠障碍，可能会持续数月。根据最近的研究，SARS-CoV-2 感染会导致线粒体功能长期中断，显着改变细胞能量代谢。我们的研究采用透射电子显微镜揭示了 Long COVID 患者独特的线粒体结构异常，特别是包括显着肿胀、嵴破裂和整体不规则形态，这些共同表明严重的线粒体痛苦。我们注意到超氧化物歧化酶 1 水平升高，这是氧化应激信号和自噬相关的 4B 半胱氨酸肽酶水平升高，表明线粒体自噬中断。重要的是，我们的分析还发现这些患者的循环游离线粒体 DNA （ccf-mtDNA） 水平降低，作为该病症的新型生物标志物。这些发现强调了持续性线粒体功能障碍在 Long COVID 发病机制中的关键作用。进一步探索病毒后线粒体功能障碍的细胞和分子机制至关重要，特别是对于了解自身免疫反应和潜在病毒的重新激活在使这些情况持续存在中的作用。 这种全面的理解可以为旨在减轻长期 COVID 慢性影响的靶向治疗干预措施铺平道路。通过利用循环 ccf-mtDNA 和其他新型线粒体生物标志物，我们可以增强我们的诊断能力并改善对这种复杂综合征的管理。