Abstract

SARS‐CoV‐2 – induced COVID‐19 causes acute respiratory distress syndrome (ARDS) and multiorgan failure. COVID‐19 can also cause psycho‐social problems, including increased alcohol consumption and consequent complications. Alcohol abuse is recognized as an independent factor that increases by three‐ to four‐fold the incidence of ARDS, a severe form of acute lung injury with a mortality rate of 40 to 50 percent. This translates to tens of thousands of excess deaths in the United States each year from alcohol‐associated lung injury. We developed a combined ARDS and alcohol abuse mouse model by intratracheally instilling the S1 subunit of SARS‐CoV‐2 Spike protein in K18‐hACE2 transgenic mice that express the human angiotensin‐converting enzyme 2 (ACE2) receptor for SARS‐CoV‐2 and which are kept on an ethanol diet. 72 hours after S1SP instillation, mice kept on the ethanol diet exhibited a strong decline in body weight, a dramatic increase in white blood cell content of bronchoalveolar lavage fluid (BALF), and an augmented “cytokine storm”, compared to S1SP treated mice on control diet. Histologic examination of lung tissue demonstrated abnormal recruitment of immune cells in the alveolar space, destructive effects on parenchymal architecture, and an overall worsening of the lung injury score (LIS) of S1SP‐ and alcohol‐treated animals. Along with the activation of pro‐inflammatory biomarkers (NF‐κB, STAT3, NLRP3 inflammasome), lung tissue homogenates from mice on alcohol diet, demonstrated overexpression of ACE2 compared to mice on control diet. In summary, K18‐hACE2 transgenic mice on an alcohol diet exhibit a more severe S1SP‐induced ARDS than corresponding mice on a control diet and may thus represent a useful model for the development of therapeutic interventions against alcohol‐exacerbated COVID‐19.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.