Table 1_Proteomic and metabolomic analysis of serum in women infected with COVID-19 during late pregnancy.docx

IntroductionTo 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.
MethodsThe 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.
ResultsThe 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.
ConclusionsThis 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.

引言 本研究旨在探究妊娠晚期感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）女性的血清蛋白质组与代谢组变化，及其对胎儿发育的潜在影响。
方法 本研究的新型冠状病毒肺炎（COVID-19）组（n=31）纳入了妊娠晚期确诊感染SARS-CoV-2且已分娩的女性；对照组（n=30）则纳入同期妊娠未受感染的女性。本研究采用数据非依赖采集（data-independent acquisition, DIA）蛋白质组学与超高效液相色谱-四极杆飞行时间质谱（ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry, UPLC-Q-TOF-MS）代谢组学技术，对两组足月妊娠女性的血清样本进行分析。对照组血清样本于分娩前1周采集，COVID-19组血清样本则于发热发作后2天内采集。通过生物信息学数据分析比较两组间的差异。对于与SARS-CoV-2感染显著相关的蛋白质与代谢物，本研究采用MetaboAnalyst 6.0进行代谢通路富集分析，并绘制妊娠晚期女性感染SARS-CoV-2的潜在靶点与通路图。
结果 与对照组相比，COVID-19组的剖宫产率、产后生殖道感染发生率及胎儿窘迫发生率均显著升高。差异蛋白质组学分析显示，SAA1、SAA2、IPO7、WDR19及BAZ1A等蛋白质的表达发生调控，这些蛋白参与视觉、皮肤及肢体发育等生物学过程。代谢组学分析鉴定出关键差异代谢物，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-酮及环胞苷，这些代谢物参与核黄素代谢、苯丙氨酸、酪氨酸和色氨酸生物合成及精氨酸生物合成通路。蛋白质组与代谢组整合分析显示，精氨酸生物合成、类固醇激素生物合成及脂肪酸降解等代谢通路发生显著紊乱。
结论 本研究阐明了妊娠晚期女性感染SARS-CoV-2后主要的蛋白质组与代谢组学变化。本研究通过多组学综合数据，解析了妊娠晚期女性感染SARS-CoV-2的潜在分子机制。上述研究结果为未来探究SARS-CoV-2感染对母婴健康的影响提供了新的研究视角与潜在靶点。