Abstract：
BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV), which has a wide geographic distribution. The primary clinical manifestations of SFTS are fever and thrombocytopenia, with multiorgan failure being the leading cause of death. While most patients recover with treatment, little is known about the potential long-term metabolic effects of SFTSV infection.
OBJECTIVE: This study aimed to shed light on dysregulated metabolic pathways and cytokine responses following SFTSV infection, which pose significant risks to the short-term and long-term health of affected individuals.
METHODS: Fourteen laboratory-confirmed clinical SFTS cases and thirty-eight healthy controls including 18 SFTSV IgG-positive and 20 IgG-negative individuals were recruited from Taizhou city of Zhejiang province, Eastern China. Inclusion criteria of healthy controls included residing in the study area for at least one year, absence of fever or other symptoms in the past two weeks, and no history of SFTS diagnosis. Ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to obtain the relative abundance of plasma metabolites. Short-term metabolites refer to transient alterations present only during SFTSV infection, while long-term metabolites persistently deviate from normal levels even after recovery from SFTSV infection. Additionally, the concentrations of 12 cytokines were quantified through fluorescence intensity measurements. Differential metabolites were screened using orthogonal projections to latent structures discriminant analysis (OPLS-DA) and the Wilcoxon rank test. Metabolic pathway analysis was performed using MetaboAnalyst. Between-group differences of metabolites and cytokines were examined using the Wilcoxon rank test. Correlation matrices between identified metabolites and cytokines were analyzed using Spearman\'s method.
CONCLUSIONS: We screened 122 long-term metabolites and 108 short-term metabolites by analytical comparisons and analyzed their correlations with 12 cytokines. Glycerophospholipid metabolism (GPL) was identified as a significant short-term metabolic pathway suggesting that the activation of GPL might be linked to the self-replication of SFTSV, whereas pentose phosphate pathway and alanine, aspartate, and glutamate metabolism were indicated as significant long-term metabolic pathways playing a role in combating long-standing oxidative stress in the patients. Furthermore, our study suggests a new perspective that α-ketoglutarate could serve as a dietary supplement to protect recovering SFTS patients.
OBJECTIVE: This study aimed to shed light on dysregulated metabolic pathways and cytokine responses following SFTSV infection, which pose significant risks to the short-term and long-term health of affected individuals.
METHODS: Fourteen laboratory-confirmed clinical SFTS cases and thirty-eight healthy controls including 18 SFTSV IgG-positive and 20 IgG-negative individuals were recruited from Taizhou city of Zhejiang province, Eastern China. Inclusion criteria of healthy controls included residing in the study area for at least one year, absence of fever or other symptoms in the past two weeks, and no history of SFTS diagnosis. Ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to obtain the relative abundance of plasma metabolites. Short-term metabolites refer to transient alterations present only during SFTSV infection, while long-term metabolites persistently deviate from normal levels even after recovery from SFTSV infection. Additionally, the concentrations of 12 cytokines were quantified through fluorescence intensity measurements. Differential metabolites were screened using orthogonal projections to latent structures discriminant analysis (OPLS-DA) and the Wilcoxon rank test. Metabolic pathway analysis was performed using MetaboAnalyst. Between-group differences of metabolites and cytokines were examined using the Wilcoxon rank test. Correlation matrices between identified metabolites and cytokines were analyzed using Spearman\'s method.
CONCLUSIONS: We screened 122 long-term metabolites and 108 short-term metabolites by analytical comparisons and analyzed their correlations with 12 cytokines. Glycerophospholipid metabolism (GPL) was identified as a significant short-term metabolic pathway suggesting that the activation of GPL might be linked to the self-replication of SFTSV, whereas pentose phosphate pathway and alanine, aspartate, and glutamate metabolism were indicated as significant long-term metabolic pathways playing a role in combating long-standing oxidative stress in the patients. Furthermore, our study suggests a new perspective that α-ketoglutarate could serve as a dietary supplement to protect recovering SFTS patients.
摘要：
背景：严重发热伴血小板减少综合征（SFTS）是由SFTS病毒（SFTSV）引起的新兴传染病，具有广泛的地理分布。SFTS的主要临床表现是发热和血小板减少,多器官衰竭是导致死亡的主要原因。虽然大多数患者通过治疗康复，对SFTSV感染的潜在长期代谢作用知之甚少。
目的：本研究旨在揭示SFTSV感染后代谢通路和细胞因子反应失调，这对受影响个体的短期和长期健康构成重大风险。
方法：从浙江省台州市招募了14例实验室确诊的临床SFTS病例和38例健康对照，其中包括18例SFTSVIgG阳性和20例IgG阴性。中国东部。纳入健康对照的标准包括居住在研究区域至少一年，过去两周没有发烧或其他症状，无SFTS诊断史。超高效液相色谱-质谱(UHPLC-MS)用于获得血浆代谢物的相对丰度。短期代谢物是指仅在SFTSV感染期间出现的短暂改变，而即使在SFTSV感染恢复后，长期代谢物仍持续偏离正常水平。此外,通过荧光强度测量对12种细胞因子的浓度进行定量.使用正交投影到潜在结构判别分析（OPLS-DA）和Wilcoxon秩检验来筛选差异代谢物。使用MetaboAnalyst进行代谢途径分析。使用Wilcoxon秩检验检查代谢物和细胞因子的组间差异。使用Spearman方法分析鉴定的代谢物和细胞因子之间的相关性矩阵。
结论：我们通过分析比较筛选了122种长期代谢物和108种短期代谢物，并分析了它们与12种细胞因子的相关性。甘油磷脂代谢（GPL）被认为是一个重要的短期代谢途径，表明GPL的激活可能与SFTSV的自我复制有关。而磷酸戊糖途径和丙氨酸，天冬氨酸,和谷氨酸代谢被认为是显著的长期代谢途径在对抗患者长期的氧化应激中起作用。此外，我们的研究提出了一个新的观点,即α-酮戊二酸可以作为膳食补充剂来保护正在康复的SFTS患者.
目的：本研究旨在揭示SFTSV感染后代谢通路和细胞因子反应失调，这对受影响个体的短期和长期健康构成重大风险。
方法：从浙江省台州市招募了14例实验室确诊的临床SFTS病例和38例健康对照，其中包括18例SFTSVIgG阳性和20例IgG阴性。中国东部。纳入健康对照的标准包括居住在研究区域至少一年，过去两周没有发烧或其他症状，无SFTS诊断史。超高效液相色谱-质谱(UHPLC-MS)用于获得血浆代谢物的相对丰度。短期代谢物是指仅在SFTSV感染期间出现的短暂改变，而即使在SFTSV感染恢复后，长期代谢物仍持续偏离正常水平。此外,通过荧光强度测量对12种细胞因子的浓度进行定量.使用正交投影到潜在结构判别分析（OPLS-DA）和Wilcoxon秩检验来筛选差异代谢物。使用MetaboAnalyst进行代谢途径分析。使用Wilcoxon秩检验检查代谢物和细胞因子的组间差异。使用Spearman方法分析鉴定的代谢物和细胞因子之间的相关性矩阵。
结论：我们通过分析比较筛选了122种长期代谢物和108种短期代谢物，并分析了它们与12种细胞因子的相关性。甘油磷脂代谢（GPL）被认为是一个重要的短期代谢途径，表明GPL的激活可能与SFTSV的自我复制有关。而磷酸戊糖途径和丙氨酸，天冬氨酸,和谷氨酸代谢被认为是显著的长期代谢途径在对抗患者长期的氧化应激中起作用。此外，我们的研究提出了一个新的观点,即α-酮戊二酸可以作为膳食补充剂来保护正在康复的SFTS患者.
