Department of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences of Ribeirão Preto-FCFRP, University of Sao Paulo-USP, Ribeirão Preto 14040-903, SP, Brazil.
Postgraduate Program in Basic and Applied Immunology-PPGIBA, Institute of Biological Sciences, Federal University of Amazonas-UFAM, Manaus 69080-900, AM, Brazil.
Cells. 2023 Jul 26;12(15):1938. doi: 10.3390/cells12151938.
SARS-CoV-2 infection triggers distinct patterns of disease development characterized by significant alterations in host regulatory responses. Severe cases exhibit profound lung inflammation and systemic repercussions. Remarkably, critically ill patients display a "lipid storm", influencing the inflammatory process and tissue damage. Sphingolipids (SLs) play pivotal roles in various cellular and tissue processes, including inflammation, metabolic disorders, and cancer. In this study, we employed high-resolution mass spectrometry to investigate SL metabolism in plasma samples obtained from control subjects ( = 55), COVID-19 patients ( = 204), and convalescent individuals ( = 77). These data were correlated with inflammatory parameters associated with the clinical severity of COVID-19. Additionally, we utilized RNAseq analysis to examine the gene expression of enzymes involved in the SL pathway. Our analysis revealed the presence of thirty-eight SL species from seven families in the plasma of study participants. The most profound alterations in the SL species profile were observed in patients with severe disease. Notably, a predominant sphingomyelin (SM d18:1) species emerged as a potential biomarker for COVID-19 severity, showing decreased levels in the plasma of convalescent individuals. Elevated SM levels were positively correlated with age, hospitalization duration, clinical score, and neutrophil count, as well as the production of IL-6 and IL-8. Intriguingly, we identified a putative protective effect against disease severity mediated by SM (d18:1/24:0), while ceramide (Cer) species (d18:1/24:1) and (d18:1/24:0)were associated with increased risk. Moreover, we observed the enhanced expression of key enzymes involved in the SL pathway in blood cells from severe COVID-19 patients, suggesting a primary flow towards Cer generation in tandem with SM synthesis. These findings underscore the potential of SM as a prognostic biomarker for COVID-19 and highlight promising pharmacological targets. By targeting sphingolipid pathways, novel therapeutic strategies may emerge to mitigate the severity of COVID-19 and improve patient outcomes.
SARS-CoV-2 感染会引发宿主调节反应的显著改变，从而导致不同的疾病发展模式。严重病例表现出严重的肺部炎症和全身反应。值得注意的是，重症患者表现出“脂质风暴”，影响炎症过程和组织损伤。鞘脂类（SLs）在包括炎症、代谢紊乱和癌症在内的各种细胞和组织过程中发挥关键作用。在这项研究中，我们使用高分辨率质谱法研究了来自对照受试者（=55）、COVID-19 患者（=204）和康复受试者（=77）的血浆样本中的 SL 代谢。这些数据与 COVID-19 临床严重程度相关的炎症参数相关联。此外，我们还利用 RNAseq 分析研究了 SL 途径中酶的基因表达。我们的分析显示，研究参与者的血浆中存在来自七个家族的 38 种 SL 物种。在严重疾病患者中，SL 物种谱的变化最为显著。值得注意的是，一种主要的神经酰胺（SM d18：1）物种作为 COVID-19 严重程度的潜在生物标志物出现，在康复个体的血浆中水平降低。SM 水平升高与年龄、住院时间、临床评分和中性粒细胞计数以及 IL-6 和 IL-8 的产生呈正相关。有趣的是，我们确定了一种由 SM（d18：1/24：0）介导的针对疾病严重程度的潜在保护作用，而神经酰胺（Cer）物种（d18：1/24：1）和（d18：1/24：0）与增加的风险相关。此外，我们观察到严重 COVID-19 患者血液细胞中参与 SL 途径的关键酶的表达增强，表明 SM 合成与 Cer 生成之间存在主要的流动。这些发现强调了 SM 作为 COVID-19 预后生物标志物的潜力，并突出了有前途的药物靶点。通过靶向鞘脂途径，可能会出现新的治疗策略来减轻 COVID-19 的严重程度并改善患者的结局。
