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Reviews of "Epigenetic Liquid Biopsies Reveal Elevated Vascular Endothelial Cell Turnover and Erythropoiesis in Asymptomatic COVID-19 Patients"

Reviewers: K Frontzek (University College London) | 📗📗📗📗◻️ • S Chatterjee (University of Pennsylvania) | 📘📘📘📘📘

Published onSep 12, 2023
Reviews of "Epigenetic Liquid Biopsies Reveal Elevated Vascular Endothelial Cell Turnover and Erythropoiesis in Asymptomatic COVID-19 Patients"
key-enterThis Pub is a Review of
Epigenetic liquid biopsies reveal elevated vascular endothelial cell turnover and erythropoiesis in asymptomatic COVID-19 patients
Epigenetic liquid biopsies reveal elevated vascular endothelial cell turnover and erythropoiesis in asymptomatic COVID-19 patients
Description

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.

To read the original manuscript, click the link above.

Summary of Reviews: This preprint analyzes cell-free DNA methylation patterns in COVID-19 patients to assess tissue damage and cellular turnover. The two reviewers provided positive feedback on the study's rationale, methods, and findings. They lauded the use of liquid biopsies to non-invasively monitor COVID-19 severity and progression. Both reviewers provided a clear summary of the main claims and key results showing elevated cfDNA levels in severe patients from various cell types. Reviewer 1 suggested analyzing fatal cases if available to determine if cfDNA correlates with mortality. Reviewer 2 identified some limitations around confounding factors, stratification, effect sizes, and transparency through data availability. Overall, the reviewers evaluated the preprint positively and recognized its potential significance, giving constructive feedback for the authors to strengthen the manuscript. The reviewers deemed this preprint to be reliable and indicated it could be informative pending revisions addressing the limitations raised.

Reviewer 1 (Karl F…) | 📗📗📗📗◻️

Reviewer 2 (Shampa C…) | 📘📘📘📘📘

RR:C19 Strength of Evidence Scale Key

📕 ◻️◻️◻️◻️ = Misleading

📙📙 ◻️◻️◻️ = Not Informative

📒📒📒 ◻️◻️ = Potentially Informative

📗📗📗📗◻️ = Reliable

📘📘📘📘📘 = Strong

To read the reviews, click the links below. 

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