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Publication Date


Publication Title

The American Journal of Pathology


Article in Press






During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, alcohol consumption increased markedly. Nearly one in four adults reported drinking more alcohol to cope with stress. Chronic alcohol abuse is now recognized as a factor complicating the course of acute respiratory distress syndrome. and increasing mortality. To investigate the mechanisms behind this interaction, we developed a combined acute respiratory distress syndrome and chronic alcohol abuse mouse model by intratracheally instilling the S1 subunit of SARS-CoV-2 spike protein (S1SP) in K18-human angiotensin-converting enzyme 2 (ACE2) transgenic mice that express the human ACE2 receptor for SARS-CoV-2 and are kept on an ethanol diet. Seventy-two hours after S1SP instillation, mice on an ethanol diet showed a strong decrease in body weight, a dramatic increase in white blood cell content of bronchoalveolar lavage fluid, and an augmented cytokine storm, compared with S1SP-treated mice on a control diet. Histologic examination of lung tissue showed abnormal recruitment of immune cells in the alveolar space, abnormal parenchymal architecture, and worsening Ashcroft score in S1SP- and alcohol-treated animals. Along with the activation of proinflammatory biomarkers (NF-κB, STAT3, NLRP3 inflammasome), lung tissue homogenates from mice on an alcohol diet showed overexpression of ACE2 compared with mice on a control diet. This model could be useful for the development of therapeutic approaches against alcohol-exacerbated coronavirus disease 2019.


Copyright © 2022 American Society for Investigative Pathology.

This is an open access article under the Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license.

Original Publication Citation

Solopov, P. A., Colunga Biancatelli, R. M. L. C., & Catravas, J. D. (2022). Alcohol increases lung angiotensin-converting enzyme 2 expression and exacerbates severe acute respiratory syndrome coronavirus 2 spike protein subunit 1-induced acute lung injury in K18-hACE2 transgenic mice. The American Journal of Pathology, Article in press, 1-11.


0000-0002-1705-027X (Solopov), 0000-0002-1174-3876 (Biancatelli), 0000-0002-5098-295X (Catravas)