Duan Lian, Yin Huamin, Liu Jiaxin, Wang Wenhang, Huang Peijun, Liu Li, Shen Jingling, Wang Zhendong
Central Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Institute of Life Sciences, College of Life and Environmental Sciences, Wenzhou University, Wenzhou, 325035, China.
Mol Psychiatry. 2025 May;30(5):2108-2118. doi: 10.1038/s41380-024-02822-z. Epub 2024 Nov 9.
Maternal COVID-19 infection increases the incidence of neurodevelopmental disorders (NDDs) in offspring, although the underlying mechanisms have not been elucidated. This study demonstrated that COVID-19 infection during pregnancy disrupted the balance of maternal and fetal immune environments, driving alterations in astrocytes, endothelial cells, and excitatory neurons. A risk score was established using 47 unique genes in the single-cell transcriptome of gestational mothers. The high risk score in CD4 proliferating T cell level served as an indicator for increased risk of offspring NDDs. Summary-based Mendelian randomization and phenome-wide association study analyses were conducted to identify the causal association of the transcriptional changes with the increased risk of offspring NDDs. Additionally, 10 drugs were identified as potential therapeutic candidates. Our findings support a model where the maternal COVID-19 infection changed the levels of CD4 proliferating T cells, leading to the alterations of astrocytes, endothelial cells, and excitatory neurons in offspring, contributing to the increased risk of NDDs in these individuals.
孕妇感染新冠病毒会增加后代神经发育障碍（NDDs）的发病率，尽管其潜在机制尚未阐明。本研究表明，孕期感染新冠病毒会破坏母婴免疫环境的平衡，导致星形胶质细胞、内皮细胞和兴奋性神经元发生改变。利用妊娠母亲单细胞转录组中的47个独特基因建立了一个风险评分。CD4增殖T细胞水平的高风险评分可作为后代患NDDs风险增加的指标。进行了基于汇总的孟德尔随机化和全表型关联研究分析，以确定转录变化与后代患NDDs风险增加之间的因果关系。此外，还确定了10种药物作为潜在的治疗候选药物。我们的研究结果支持这样一种模型，即孕妇感染新冠病毒会改变CD4增殖T细胞的水平，导致后代星形胶质细胞、内皮细胞和兴奋性神经元发生改变，从而增加这些个体患NDDs的风险。
