Lung Remodeling Regions in Long-Term Coronavirus Disease 2019 Feature Basal Epithelial Cell Reprogramming

• Published in: The American journal of pathology Vol. 193; no. 6; pp. 680 - 689
• Main Authors: Wu, Kangyun, Zhang, Yong, Austin, Stephen R., Yin-Declue, Huiqing, Byers, Derek E., Crouch, Erika C., Holtzman, Michael J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2023
• Subjects: Cellular Reprogramming; COVID-19; Epithelial Cells; Humans; Lung; SARS-CoV-2
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/j.ajpath.2023.02.005

Respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (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, the current study examined a series of consecutive fatal cases of coronavirus disease 2019 (COVID-19) that came to autopsy at 27 to 51 days after hospital admission. In each patient, a stereotyped bronchiolar-alveolar pattern of lung remodeling was identified with basal epithelial cell hyperplasia, immune activation, and mucinous differentiation. Remodeling regions featured macrophage infiltration and apoptosis and a marked depletion of alveolar type 1 and 2 epithelial cells. This pattern closely resembled findings from an experimental model of post-viral lung disease that requires basal-epithelial stem cell growth, immune activation, and differentiation. Together, these 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. [Display omitted]