Epigenetic liquid biopsies reveal elevated vascular endothelial cell turnover and erythropoiesis in asymptomatic COVID-19 patients

  1. Roni Ben-Ami
  2. Netanel Loyfer
  3. Eden Cohen
  4. Gavriel Fialkoff
  5. Israa Sharkia
  6. Naama Bogot
  7. Danit Kochan
  8. George Kalak
  9. Amir Jarjoui
  10. Chen Chen-Shuali
  11. Hava Azulai
  12. Hezi Barhoum
  13. Nissim Arish
  14. Moshe M Greenberger
  15. David Vellema
  16. Ramzi Kurd
  17. Eli Ben Chetrit
  18. Davina Bohm
  19. Talya Wolak
  20. Ahmad Quteineh
  21. Gordon Cann
  22. Benjamin Glaser
  23. Nir Friedman
  24. Tommy Kaplan
  25. Ruth Shemer
  26. Ariel Rokach
  27. Yuval Dor

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Abstract

The full spectrum of tissues affected by SARS-CoV-2 infection is crucial for deciphering the heterogenous clinical course of COVID-19. Here, we analyzed DNA methylation and histone modification patterns in circulating chromatin to assess cell type-specific turnover in severe and asymptomatic COVID-19 patients, in relation to clinical outcome. Patients with severe COVID-19 had a massive elevation of circulating cell-free DNA (cfDNA) levels, which originated in lung epithelial cells, cardiomyocytes, vascular endothelial cells and erythroblasts, suggesting increased cell death or turnover in these tissues. The immune response to infection was reflected by elevated B cell and monocyte/macrophage cfDNA levels, and by evidence of an interferon response in cells prior to cfDNA release. Strikingly, monocyte/macrophage cfDNA levels (but not monocyte counts), as well as lung epithelium cfDNA and vascular endothelial cfDNA, predicted clinical deterioration and duration of hospitalization. Asymptomatic patients had elevated levels of immune-derived cfDNA but did not show evidence of pulmonary or cardiac damage. Surprisingly, these patients showed elevated levels of vascular endothelial cell and erythroblast cfDNA, suggesting that sub-clinical vascular and erythrocyte turnover are universal features of COVID-19, independent of disease severity. Epigenetic liquid biopsies provide non-invasive means of monitoring COVID-19 patients, and reveal sub-clinical vascular damage and red blood cell turnover.

Article activity feed

  1. Rapid Reviews Infectious Diseases

    Shampa Chatterjee

    Review 2: "Epigenetic Liquid Biopsies Reveal Elevated Vascular Endothelial Cell Turnover and Erythropoiesis in Asymptomatic COVID-19 Patients"

    Overall, the reviewers evaluated the preprint positively and recognized its potential significance, giving constructive feedback for the authors to strengthen the manuscript.

  2. Rapid Reviews Infectious Diseases

    Karl Frontzek

    Review 1: "Epigenetic Liquid Biopsies Reveal Elevated Vascular Endothelial Cell Turnover and Erythropoiesis in Asymptomatic COVID-19 Patients"

    Overall, the reviewers evaluated the preprint positively and recognized its potential significance, giving constructive feedback for the authors to strengthen the manuscript.

  4. Version published to 10.1101/2023.07.28.550957v1 on bioRxiv