Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Laboratory of Biochemistry, Faculty of Health Care and Nursing, Juntendo University, Chiba, Japan.
FASEB J. 2024 Jul 31;38(14):e23827. doi: 10.1096/fj.202401099R.
The COVID-19 pandemic, caused by SARS-CoV-2, has had a significant worldwide impact, affecting millions of people. COVID-19 is characterized by a heterogenous clinical phenotype, potentially involving hyperinflammation and prolonged tissue damage, although the exact underlying mechanisms are yet to be fully understood. Sphingolipid metabolites, which govern cell survival and proliferation, have emerged as key players in inflammatory signaling and cytokine responses. Given the complex metabolic pathway of sphingolipids, this study aimed to understand their potential role in the pathogenesis of COVID-19. We conducted a comprehensive examination of sphingolipid modulations across groups classified based on disease severity, incorporating a time-course in serum and urine samples. Several sphingolipids, including sphingosine, lactosylceramide, and hexosylceramide, emerged as promising indicators of COVID-19 severity, as validated by correlation analyses conducted on both serum and urine samples. Other sphingolipids, such as sphingosine 1-phosphate, ceramides, and deoxy-dihydroceramides, decreased in both COVID-19 patients and individuals with non-COVID infectious diseases. This suggests that these sphingolipids are not specifically associated with COVID-19 but rather with pathological conditions caused by infectious diseases. Our analysis of urine samples revealed elevated levels of various sphingolipids, with changes dependent on disease severity, potentially highlighting the acute kidney injury associated with COVID-19. This study illuminates the intricate relationship between disturbed sphingolipid metabolism, COVID-19 severity, and clinical factors. These findings provide valuable insights into the broader landscape of inflammatory diseases.
新型冠状病毒病（COVID-19）由 SARS-CoV-2 引起，对全球造成了重大影响，影响了数百万人。COVID-19 的临床表型具有异质性，可能涉及过度炎症和组织损伤的持续存在，尽管确切的潜在机制尚未完全了解。控制细胞存活和增殖的神经鞘脂代谢物已成为炎症信号和细胞因子反应的关键参与者。鉴于神经鞘脂代谢物的复杂代谢途径，本研究旨在了解其在 COVID-19 发病机制中的潜在作用。我们对基于疾病严重程度分类的组中神经鞘脂的调节进行了全面检查，纳入了血清和尿液样本中的时间过程。几种神经鞘脂，包括神经鞘氨醇、乳糖神经酰胺和己糖神经酰胺，被证实在血清和尿液样本的相关分析中是 COVID-19 严重程度的有希望的指标。其他神经鞘脂，如神经鞘氨醇 1-磷酸、神经酰胺和去氧二氢神经酰胺，在 COVID-19 患者和非 COVID 传染病患者中均减少。这表明这些神经鞘脂并非特异性地与 COVID-19 相关，而是与传染病引起的病理状况相关。我们对尿液样本的分析显示，各种神经鞘脂水平升高，变化取决于疾病严重程度，这可能突出了与 COVID-19 相关的急性肾损伤。本研究阐明了受干扰的神经鞘脂代谢、COVID-19 严重程度和临床因素之间的复杂关系。这些发现为炎症性疾病的更广泛领域提供了有价值的见解。
