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Lung remodeling regions in long-term Covid-19 feature basal epithelial cell reprogramming - American Journal of Pathology (AJP) Pre-proof

Mary Wilson

Well-known member
Journal Pre-proof: This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Revised Date: 8 February 2023
Accepted Date: 13 February 2023
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Published: March 01, 2023

DOI: https://doi.org/10.1016/j.ajpath.2023.02.005

Kangyun Wu, Yong Zhang, Stephen R. Austin, Huqing Yin Declue, Derek E. Byers, Erika C. Crouch,
Michael J. Holtzman

Abstract

Respiratory viruses, including SARS-CoV-2, can trigger chronic lung disease that persists and even progresses after expected clearance of infectious virus. To gain an understanding of this process, we examined a series of consecutive fatal cases of Covid-19 that came to autopsy at 27-51 d after hospital admission. In each patient, we identify a stereotyped bronchiolar-alveolar pattern of lung remodeling with basal epithelial cell hyperplasia, immune activation, and mucinous differentiation. Remodeling regions also feature macrophage infiltration and apoptosis and a marked depletion of alveolar type 1 and 2 epithelial cells. This entire pattern closely resembles findings from an experimental model of post-viral lung disease that requires basal-epithelial stem cell growth, immune activation, and differentiation. Together, the results provide evidence of basal epithelial cell reprogramming in long-term Covid-19 and thereby yield a pathway for explaining and correcting lung dysfunction in this type of disease.

https://ajp.amjpathol.org/action/showPdf?pii=S0002-9440(23)00056-1
 
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