Unraveling the pathogenic interplay between SARS-CoV-2 and polycystic ovary syndrome using bioinformatics and experimental validation.

The prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among polycystic ovary syndrome (PCOS) is significantly higher than in the general population. However, the mechanisms underlying this remain obscure. This study aimed to explore the mechanisms by identifying the genetic signature of SARS-CoV-2 infection in PCOS. In the present study, a total of 27 common differentially expressed genes (DEGs) were selected for subsequent analyses. Functional analyses showed that immunity and hormone-related pathways collectively participated in the development and progression of PCOS and SARS-CoV-2 infection. Under these, 7 significant hub genes were identified, including S100A9, MMP9, TLR2, THBD, ITGB2, ICAM1, and CD86 by using the algorithm in Cytoscape. Furthermore, hub gene expression was confirmed in the validation set, PCOS clinical samples, and mouse model. Immune microenvironment analysis with the CIBERSORTx database demonstrated that the hub genes were significantly correlated with T cells, dendritic cells, mast cells, B cells, NK cells, and eosinophils and positively correlated with immune scores. Among the hub genes, S100A9, MMP9, THBD, ITGB2, CD86, and ICAM1 demonstrated potential as possible diagnostic markers for COVID-19 and PCOS. In addition, we established the interaction networks of ovary-specific genes, transcription factors, miRNAs, drugs, and chemical compounds with hub genes with NetworkAnalyst. This work uncovered the common pathogenesis and genetic signature of PCOS and SARS-CoV-2 infection, which might provide a theoretical basis and innovative ideas for further mechanistic research and drug discovery of the comorbidity of the two diseases.