COVID-19 of differing severity: from bulk to single-cell expression data analysis

ABSTRACT

Coronavirus disease 2019 (COVID-19) is raging worldwide and causes an immense disease burden. Despite this, the biomarkers and targeting drugs of COVID-19 of differing severity remain largely unknown. Based on the GSE164805 dataset, we identified modules most critical for mild COVID-19 (mCOVID-19) and severe COVID-19 (sCOVID-19) through WGCNA, respectively. We subsequently constructed a protein–protein interaction network, and detected 16 hub genes for mCOVID-19 and 10 hub genes for sCOVID-19, followed by the prediction of upstream transcription factors (TFs) and kinases. The enrichment analysis then showed downregulation of TNFA signaling via NFKB for mCOVID-19, as well as downregulation of MYC targets V1 for sCOVID-19. Infiltration degrees of many immune cells, such as macrophages, were also sharply different between mCOVID-19 and sCOVID-19 samples. Predicted protein targeting drugs with the highest scores nearly all belong to naturally derived or synthetic glucocorticoids. For the two single-cell RNA-seq datasets, we explored the expression distribution of hub genes for mCOVID-19/sCOVID-19 in each cell type. The expression levels of PRKCA, MCM5, TYMS, RBBP4, BCL6, FLOT1, KDM6B, and TLR2 were found to be cell-type-specific. Furthermore, the expression levels of 10 hub genes for mCOVID-19 were significantly upregulated in PBMCs between eight healthy controls and eight mCOVID-19 patients at our institution. Collectively, we detected critical modules, pathways, TFs, kinases, immune cells, targeting drugs, hub genes, and their expression distributions in different cell types that may involve the pathogenesis of COVID-19 of differing severity, which may propel earlier diagnosis and more effective treatment of this intractable disease in the future.

KEYWORDS:

• COVID-19
• bulk
• single-cell

Acknowledgements

We would like to thank Yali Zhou from Department of Microbiology, Faculty of Basic Medical Sciences, Guilin Medical University for the proofreading of our manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s). All coauthors demonstrated no conflict of interest in connection with the present study.

Authors’ contributions

Study design: N.Z and J.D.; Administrative support: X.X.D., M.K.Q., and C.Y.T.; Data analysis and visualization: L.L.T., M.H., H.F.F., H.Y.Z., and Y.Y. Manuscript writing: L.L.T., T.C. and N.Z.

Ethical Approval and Consent to participate

The medical research ethics committee of Microbiology Laboratory, Nanjing Municipal Center for Disease Control and Prevention identified and approved study design of the current study.

Availability of supporting data

The dataset used for the current study can be achieved from the GEO website.

Supplementary Material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/15384101.2023.2239620

Authors’ information

L.L.T., M.H., H.F.F., H.Y.Z., X.X.D., M.K.Q., C.Y.T., Y.Y., T.C., and N.Z. are from Nanjing Municipal Center for Disease Control and Prevention. In addition, T.C. is from Department of Urology, The First Affiliated Hospital of Nanjing Medical University.

Additional information

Funding

This study was supported by Jiangsu Funding Program for Excellent Postdoctoral Talent (2022ZB730) and Nanjing Important Science & Technology Specific Projects (2021–11005).