CXCL10 May Be Responsible for Susceptibility to Pulmonary Embolism in COVID-19 Patients

Abstract

Background

Although the potential of coronavirus disease 2019 (COVID-19) patients to develop pulmonary embolism (PE) is widely recognized, the underlying mechanism has not been completely elucidated. This study aimed to identify genes common to COVID-19 and PE to reveal the underlying pathogenesis of susceptibility to PE in COVID-19 patients.

Methods

COVID-19 genes were obtained from the GEO database and the OMIM, CTD, GeneCards, and DisGeNET databases; PE genes were obtained from the OMIM, CTD, GeneCards, and DisGeNET databases. We overlapped the genes of COVID-19 and PE to obtain common genes for additional analysis, including functional enrichment, protein–protein interaction, and immune infiltration analysis. Hub genes were identified using cytoHubba, a plugin of Cytoscape, and validated using the independent datasets GSE167000 and GSE13535. The genes validated by the above datasets were further validated in clinical samples.

Results

We obtained 36 genes shared by PE and COVID-19. Functional enrichment and immune infiltration analyses revealed the involvement of cytokines and immune activation. Five genes (CCL2, CXCL10, ALB, EGF, and MKI67) were identified as hub genes common to COVID-19 and PE. CXCL10 was validated in both independent datasets (GSE167000 and GSE13535). Serum levels of CXCL10 in the COVID-19 group and the COVID-19 combined with PE group were significantly higher than those in the healthy control group (P<0.001). In addition, there were significant differences between the COVID-19 group and the COVID-19 combined with PE group (P<0.01).

Conclusion

Our study reveals common genes shared by PE and COVID-19 and identifies CXCL10 as a possible cause of susceptibility to PE in COVID-19 patients.

Graphical Abstract

Keywords:

• pulmonary embolism
• coronavirus disease 2019
• bioinformatics
• CXCL10

Abbreviations

COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; PE, pulmonary embolism; DEGs, differentially expressed genes; GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; PPI, protein–protein interaction; PAECs, pulmonary artery endothelial cells.

Data Sharing Statement

We provide details of the materials and methods in our manuscript.

Ethical Approval and Consent to Participate

This study was performed in accordance with the Helsinki declaration and was approved by the ethics committee of Henan Provincial People’s Hospital (Ethical Review 2023(97)), and written informed consent from all participants was provided for the use of their blood samples.

Acknowledgments

We sincerely thank the public databases GEO, OMIM, CTD, GeneCards, DisGeNET, and STRING for providing data for our research and Cytoscape, CIBERSORTx, and Sangerbox for analyzing data.

Disclosure

The authors declare that they have no conflicts of interest.

Additional information

Funding

This study is supported by the Natural Science Foundation of Henan Province (Yong Qi, No. 232300421122).