Towards understanding post-COVID-19 condition: A systematic meta-analysis of transcriptomic alterations with sex-specific insights, 2024, Rusu et al.

SNT Gatchaman

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Towards understanding post-COVID-19 condition: A systematic meta-analysis of transcriptomic alterations with sex-specific insights
Rusu; Monfort-Lanzas; Bertran; Barrientos-Riosalido; Solé; Mahmoudian; Aguilar; Briansó; Mohamed; Garcia; Camaron; Auguet

BACKGROUND
Post COVID-19 Condition (PCC), characterized by lingering symptoms post-acute COVID-19, poses clinical challenges, highlighting the need to understand its underlying molecular mechanisms. This meta-analysis aims to shed light on the transcriptomic landscapes and sex-specific molecular dynamics intrinsic to PCC.

METHODS
A systematic review identified three studies suitable for comprehensive meta-analysis, encompassing 135 samples (57 PCC subjects and 78 recovered subjects). We performed meta-analysis on differential gene expression, a gene set enrichment analysis of Reactome pathways, and weighted gene co-expression network analysis (WGCNA). We performed a drug and disease enrichment analysis and also assessed sex-specific differences in expression patterns.

KEY FINDINGS
A clear difference was observed in the transcriptomic profiles of PCC subjects, with 530 differentially expressed genes (DEGs) identified. Enrichment analysis revealed that the altered pathways were predominantly implicated in cell cycle processes, immune dysregulation and histone modifications. Antioxidant compounds such as hesperitin were predominantly linked to the hub genes of the DEGs. Sex-specific analyses highlighted disparities in DEGs and altered pathways in male and female PCC patients, revealing a difference in the expression of ribosomal proteins. PCC in men was mostly linked to neuro-cardiovascular disorders, while women exhibited more diverse disorders, with a high index of respiratory conditions.

CONCLUSIONS
Our study reveals the intricate molecular processes underlying PCC, highlighting that the differences in molecular dynamics between males and females could be key to understanding and effectively managing the varied symptomatology of this condition.

Link | Paywall (Computers in Biology and Medicine)
 
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In conclusion, this meta-analysis sheds light on the intricate molecular landscape and pathogenesis underlying PCC. We report a persistent immune dysregulation in patients with PCC, as well as alterations in DNA methylation and histone expression. Remarkably, our findings highlight an up-regulation of the histone family of proteins in PCC patients.

We identify of drugs with antioxidant properties, such as hesperitin, which can potentially mitigate the oxidative stress characteristic of PCC. In addition, our analysis reveals distinct sex-specific patterns, with ribosomal proteins emerging as central players in driving differential gene expression responses between males and females. These sex-specific differences extend to the associated diseases, with men exhibiting a predisposition to neuro-cardiovascular disorders, while women manifest a broader spectrum of mostly respiratory, but also renal and immunological conditions.
 
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