TY - JOUR
T1 - Epigenetic liquid biopsies reveal endothelial turnover and erythropoiesis in asymptomatic COVID-19
AU - Ben-Ami, Roni
AU - Loyfer, Netanel
AU - Cohen, Eden
AU - Fialkoff, Gavriel
AU - Sharkia, Israa
AU - Piyanzin, Sheina
AU - Bogot, Naama
AU - Kochan, Danit
AU - Kalak, George
AU - Jarjoui, Amir
AU - Chen-Shuali, Chen
AU - Azulai, Hava
AU - Barhoum, Hezi
AU - Arish, Nissim
AU - Greenberger, Moshe M.
AU - Velleman, David
AU - Kurd, Ramzi
AU - Ben-Chetrit, Eli
AU - Bohm, Davina
AU - Wolak, Talya
AU - Quteineh, Ahmad
AU - Cann, Gordon
AU - Glaser, Benjamin
AU - Friedman, Nir
AU - Kaplan, Tommy
AU - Shemer, Ruth
AU - Rokach, Ariel
AU - Dor, Yuval
N1 - Publisher Copyright:
© 2025 Ben-Ami et al.
PY - 2025/10/1
Y1 - 2025/10/1
N2 - Understanding the full spectrum of tissues affected by SARS-CoV-2 is crucial for deciphering the heterogeneous clinical course of COVID-19. We analyzed DNA methylation and histone modifications in circulating chromatin to assess cell type–specific turnover in patients ranging from asymptomatic to severe cases, in relation to clinical outcomes. Severe COVID-19 was marked by a massive el-evation of circulating cell-free DNA (cfDNA) from lung epithelium, cardiomyocytes, vascular endothelium, and erythroblasts, indicat-ing increased cell death or turnover. The immune response was reflected by elevated B-cell and monocyte/macrophage cfDNA and an interferon response before cfDNA release. Strikingly, monocyte/ macrophage cfDNA (but not monocyte counts), as well as lung epithelial and endothelial cfDNA, predicted clinical deterioration and duration of hospitalization. Asymptomatic patients had elevated immune cfDNA but no evidence of pulmonary or cardiac damage. Surprisingly, these patients showed elevated endothelial and erythroblast cfDNA, suggesting subclinical vascular and erythrocyte turnover are universal features of COVID-19, indepen-dent of disease severity. Epigenetic liquid biopsies provide a noninvasive means of monitoring COVID-19 patients and reveal subclinical vascular damage and red blood cell turnover.
AB - Understanding the full spectrum of tissues affected by SARS-CoV-2 is crucial for deciphering the heterogeneous clinical course of COVID-19. We analyzed DNA methylation and histone modifications in circulating chromatin to assess cell type–specific turnover in patients ranging from asymptomatic to severe cases, in relation to clinical outcomes. Severe COVID-19 was marked by a massive el-evation of circulating cell-free DNA (cfDNA) from lung epithelium, cardiomyocytes, vascular endothelium, and erythroblasts, indicat-ing increased cell death or turnover. The immune response was reflected by elevated B-cell and monocyte/macrophage cfDNA and an interferon response before cfDNA release. Strikingly, monocyte/ macrophage cfDNA (but not monocyte counts), as well as lung epithelial and endothelial cfDNA, predicted clinical deterioration and duration of hospitalization. Asymptomatic patients had elevated immune cfDNA but no evidence of pulmonary or cardiac damage. Surprisingly, these patients showed elevated endothelial and erythroblast cfDNA, suggesting subclinical vascular and erythrocyte turnover are universal features of COVID-19, indepen-dent of disease severity. Epigenetic liquid biopsies provide a noninvasive means of monitoring COVID-19 patients and reveal subclinical vascular damage and red blood cell turnover.
UR - https://www.scopus.com/pages/publications/105013075019
U2 - 10.26508/lsa.202503417
DO - 10.26508/lsa.202503417
M3 - Article
C2 - 40763987
AN - SCOPUS:105013075019
SN - 2575-1077
VL - 8
JO - Life Science Alliance
JF - Life Science Alliance
IS - 10
M1 - e202503417
ER -
