4.7 Article

Transcriptome and DNA methylome analysis of peripheral blood samples reveals incomplete restoration and transposable element activation after 3-months recovery of COVID-19

Journal

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2022.1001558

Keywords

SARS-cov-2; recovery; whole-genome bisulfite sequencing; transposable elements; differentially methylated regions

Funding

  1. National Natural Science Foundation of China [NSFC]
  2. Fundamental Research Funds for the Central Universities [32000488, 32170820]
  3. HUST
  4. HUST COVID-19 Rapid Response Call [2021GCRC073, 2019kfyXJJS083]
  5. National Key R&D Program of China [2020kfyXGYJ057]
  6. program for HUST Academic Frontier Youth Team [2018YFC1004500, 2018YFC1004000]

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By studying recovered COVID-19 patients, we identified transcriptomic and epigenomic features that help determine the risks of long COVID-19 and guide clinical intervention.
Comprehensive analyses showed that SARS-CoV-2 infection caused COVID-19 and induced strong immune responses and sometimes severe illnesses. However, cellular features of recovered patients and long-term health consequences remain largely unexplored. In this study, we collected peripheral blood samples from nine recovered COVID-19 patients (median age of 36 years old) from Hubei province, China, 3 months after discharge as well as 5 age- and gender-matched healthy controls; and carried out RNA-seq and whole-genome bisulfite sequencing to identify hallmarks of recovered COVID-19 patients. Our analyses showed significant changes both in transcript abundance and DNA methylation of genes and transposable elements (TEs) in recovered COVID-19 patients. We identified 425 upregulated genes, 214 downregulated genes, and 18,516 differentially methylated regions (DMRs) in total. Aberrantly expressed genes and DMRs were found to be associated with immune responses and other related biological processes, implicating prolonged overreaction of the immune system in response to SARS-CoV-2 infection. Notably, a significant amount of TEs was aberrantly activated and their activation was positively correlated with COVID-19 severity. Moreover, differentially methylated TEs may regulate adjacent gene expression as regulatory elements. Those identified transcriptomic and epigenomic signatures define and drive the features of recovered COVID-19 patients, helping determine the risks of long COVID-19, and guiding clinical intervention.

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