Endometrial gene expression differences in women with coronavirus disease 2019

Objective: To study the potential effect of COVID-19 on the endometrium of affected symptomatic women. Design: Preliminary study of the endometrial transcriptomes in women with COVID-19 through RNA sequencing. Setting: Hospital and university laboratories. Subjects: Women with COVID-19 lacking SARS-CoV-2 infection in endometrial tissue. Intervention/Exposure: Endometrial biopsy collection. Main outcomes measures: Endometrial gene expression and functional analysis of patients with COVID-19 versus uninfected individuals. Results: COVID-19 systemic disease alters endometrial gene expression in 75% of women, with patients exhibiting a preponderance of 163 up-regulated (e.g., UTS2, IFI6, IFIH1, BNIP3) and 72 down-regulated genes (e.g., CPZ, CDH3, IRF4) (FDR<0.05). A total of 161 dysregulated functions (36 up-regulated and 125 down-regulated) were typically enriched in COVID-19 endometria, including upregulation in pathways involved in response to virus and cytokine inflammation, highlighting upregulation of a COVID-19 response pathway. Conclusion: COVID-19 affects endometrial gene expression despite the absence of SARS-CoV-2 particles in endometrial tissues. Overall design: A total of 24 endometrial samples were collected for this study. Fourteen biopsies (COVID-19 group) came from COVID-19 patients hospitalized at Hospital Universitari i Politècnic La Fe (Valencia, Spain) (14); these patients had a positive result (cycle threshold, CT < 37) for SARS-CoV-2 infection indicated by real-time polymerase chain reaction (RT-PCR) of nasopharyngeal swabs. The other ten endometria (control group) were derived from patients with benign gynecological disorders not related to endometrium (negative result in a COVID-19 RT-PCR diagnostic test of nasopharyngeal swabs) of the same hospital. Then, samples with a good RNA quality (DV200 > 30%) were analyzed through RNA-seq to detect gene expression changes with an untargeted approach between both groups (COVID-19 and control). Finally, sequencing raw data were preprocessed, normalized, and functionally interpreted using bioinformatics procedures for reporting which genes and functions are altered in the endometrium due to the disease.

研究目标：探究新型冠状病毒肺炎（COVID-19）对有症状感染女性子宫内膜的潜在影响。
研究设计：通过RNA测序（RNA sequencing，RNA-seq）对新冠病毒（SARS-CoV-2）感染女性的子宫内膜转录组开展初步研究。
研究场景：医院及大学实验室。
研究对象：子宫内膜组织中未检测到新冠病毒（SARS-CoV-2）感染的新冠感染女性。
干预/暴露因素：子宫内膜活检样本采集。
主要结局指标：对比新冠感染患者与未感染个体的子宫内膜基因表达及功能分析。
研究结果：新冠全身性疾病会改变75%受检女性的子宫内膜基因表达，患者体内共存在163个上调基因（如UTS2、IFI6、IFIH1、BNIP3）以及72个下调基因（如CPZ、CDH3、IRF4），错误发现率（False Discovery Rate，FDR）<0.05。新冠感染相关子宫内膜组织中富集了共161个功能失调的通路（其中36个上调、125个下调），涵盖病毒应答及细胞因子炎症相关通路的上调，凸显了新冠特异性应答通路的激活。
研究结论：尽管子宫内膜组织中未检测到新冠病毒（SARS-CoV-2）颗粒，新冠感染仍会改变子宫内膜的基因表达谱。
整体研究设计：本研究共收集24份子宫内膜样本。其中14份活检样本归为新冠感染组，取自西班牙巴伦西亚拉费大学综合理工医院（Hospital Universitari i Politècnic La Fe）收治的新冠感染患者，这些患者经鼻咽拭子实时荧光定量聚合酶链反应（real-time polymerase chain reaction，RT-PCR）检测显示新冠病毒（SARS-CoV-2）感染结果为阳性（循环阈值CT<37）。剩余10份子宫内膜样本归为对照组，取自同一家医院的非子宫内膜相关良性妇科疾病患者，且其鼻咽拭子新冠RT-PCR诊断检测结果为阴性。随后，选取RNA完整性合格（DV200>30%）的样本通过RNA测序开展非靶向转录组表达分析，以检测两组（新冠感染组与对照组）之间的基因表达差异。最后，利用生物信息学流程对测序原始数据进行预处理、标准化及功能解读，以明确该疾病导致子宫内膜中发生改变的基因及功能通路。