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Investigating the Association between Maternal COVID-19 Infection and Modifications in the Functionality of the Immune System in Newborns
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- Author / Creator
- Ghajar, Solmaz
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Background: Maternal COVID-19 infection during pregnancy has raised prominent public health concerns - especially the possibility of long-term child health outcomes. Epigenetic changes induced by inflammatory environment in the placenta caused by anti-infection response in pregnant mother’s body, can change the gene expression patterns of fetus cells which are crucial for healthy development of the offspring. Gene expression analysis methods can be used to assess many health outcomes, including immune response, metabolic pathways, and the development of chronic disease, into the childhood years and beyond. This study aimed to evaluate the effects of a maternal COVID-19 infection on gene expression alterations of metabolic pathways in the fetus and the newborn, with a focus on innate immune system functions.
Methods: We tested gene expression data derived from umbilical cord blood cells from infants born to mothers who had a COVID-19 infection during pregnancy (n = 8) and infants whose mothers did not have COVID-19 (n = 8). The gene expression microarray dataset (GSE195938) was previously published by Jefferson et al. (2022), and the dataset and corresponding expression for 186 gene sets were sorted by the KEGG LEGACY catalog which represents canonical biological pathways in the human body. To identify gene sets impacting continuous phenotypes that capture innate immune functions, we applied the Linear Combination Test (LCT), a gene set analysis method. LCT captures the features inherent in the data to isolate gene sets based on intrinsic expression patterns.
Results: Significant differences in patterns of gene set expression in infants born to COVID-19 mothers were noted. The analysis also resulted in identifying gene sets taking part in aminoacyl tRNA biosynthesis, asthma, and systemic lupus erythematosus which demonstrated relations to inherent pattern expressions relating to innate immune functions phenotypes. The present study suggests that maternal COVID-19 infection may impact fetal immune development, and increase the risk of immune-mediated outcomes such as asthma. A statistically significant enrichment was also associated with gene sets responsible for amino acid and lipid metabolism and their relationship with immune signaling pathways. This finding suggests an association between maternal COVID-19 rounded to metabolic pathways associated with amino acid metabolism and pathways in folate synthesis, which are relevant to fetal growth and development.
Conclusion: In closing, maternal COVID-19 infection during pregnancy can lead to epigenetic changes in the fetus, which may have future effects on immune function and metabolic pathways. The gene sets and pathways presented here need further work to understand implications for offspring health. This analysis provides support for more studies on epigenetics as a mechanism for understanding how maternal infection may affect offspring development and health. It also underscores the importance of more prenatal care and addresses potential targets for prevention, in the interest of minimizing the future risk of autoimmune and allergic diseases, for infants born to COVID-19-infected-mothers. -
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- Graduation date
- Fall 2024
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- Type of Item
- Thesis
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- Degree
- Master of Science
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- License
- This thesis is made available by the University of Alberta Library with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.