Zheng Yi, Ning Jinyu, Zhu Jiang, Zhu Honglin, She Zhihua, Cai Pei
Department of Pharmacy, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China.
Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Front Immunol. 2025 Jun 11;16:1589239. doi: 10.3389/fimmu.2025.1589239. eCollection 2025.
To investigate the alterations of serum proteins and metabolomics in women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the end of pregnancy and their potential effects on fetal development.
The corona virus disease 2019 (COVID-19) group (n=31) included women in the third trimester diagnosed with SARS-CoV-2 infection and who delivered, while the control group (n=30) comprised uninfected women in the same gestational period. This study applied data-independent acquisition (DIA) proteomics and ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) metabolomics to analyze serum samples from two groups of full-term pregnant women. Serum samples in the control group were collected one week before delivery, while those in the COVID-19 group were collected within two days after the onset of fever. The differences between groups were compared by bioinformatics data analysis. For proteins and metabolites exhibiting a significant association with SARS-CoV-2, metabolic pathway enrichment was performed utilizing MetaboAnalyst 6.0, and the possible targets and pathways of SARS-CoV-2 infection in women in late pregnancy were plotted.
The incidence of cesarean section, postpartum reproductive tract infection, and fetal distress were significantly higher in the COVID-19 group compared to the control group. Differential proteomic analysis revealed the regulation of proteins such as SAA1, SAA2, IPO7, WDR19, and BAZ1A, which were involved in processes such as visual, skin and limb development. Metabolomics analysis revealed key altered metabolites, including 1-(7-methoxy-2-oxo-2H-chromen-8-yl)-3-methyl-2-oxobutylacetate, 5-(hydroxymethyl) -4-methoxy-2,5-dihydrofuran-2-one, and cyclocytidine, which were involved in the riboflavin metabolism, the phenylalanine, tyrosine and tryptophan biosynthesis, and the arginine biosynthesis. Integrative analysis of proteomic and metabolomic revealed significant disruptions in metabolic pathways, including arginine biosynthesis, steroid hormone biosynthesis, and fatty acid degradation.
This study revealed the main proteomic and metabolic effects of SARS-CoV-2 infection on women in the third trimester of pregnancy. Our comprehensive omics data elucidating the molecular mechanisms underlying SARS-CoV-2 infection in women during late pregnancy. These findings offer novel insights and potential targets for future investigations into the impact of SARS-CoV-2 infection on maternal and infant health.
研究妊娠末期感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的女性血清蛋白质和代谢组学的变化及其对胎儿发育的潜在影响。
2019冠状病毒病（COVID-19）组（n = 31）包括妊娠晚期被诊断为SARS-CoV-2感染并分娩的女性，而对照组（n = 30）由同一妊娠期未感染的女性组成。本研究应用数据非依赖采集（DIA）蛋白质组学和超高效液相色谱-四极杆飞行时间质谱联用（UPLC-Q-TOF-MS）代谢组学分析两组足月孕妇的血清样本。对照组血清样本在分娩前一周采集，而COVID-19组血清样本在发热 onset 后两天内采集。通过生物信息学数据分析比较组间差异。对于与SARS-CoV-2有显著关联的蛋白质和代谢物，利用MetaboAnalyst 6.0进行代谢途径富集，并绘制妊娠晚期女性SARS-CoV-2感染的可能靶点和途径。
COVID-19组剖宫产、产后生殖道感染和胎儿窘迫的发生率显著高于对照组。差异蛋白质组学分析揭示了SAA1、SAA2、IPO7、WDR19和BAZ1A等蛋白质的调控，这些蛋白质参与视觉、皮肤和肢体发育等过程。代谢组学分析揭示了关键的代谢物变化，包括1-(7-甲氧基-2-氧代-2H-色烯-8-基)-3-甲基-2-氧代丁基乙酸酯、5-(羟甲基)-4-甲氧基-2,5-二氢呋喃-2-酮和环胞苷，它们参与核黄素代谢、苯丙氨酸、酪氨酸和色氨酸生物合成以及精氨酸生物合成。蛋白质组学和代谢组学的综合分析揭示了代谢途径的显著破坏，包括精氨酸生物合成、类固醇激素生物合成和脂肪酸降解。
本研究揭示了SARS-CoV-2感染对妊娠晚期女性的主要蛋白质组学和代谢影响。我们的综合组学数据阐明了妊娠晚期女性SARS-CoV-2感染的分子机制。这些发现为未来研究SARS-CoV-2感染对母婴健康的影响提供了新的见解和潜在靶点。
