Abstract
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, a combined acute respiratory distress syndrome and chronic alcohol abuse mouse model was developed by intratracheally instilling the subunit 1 (S1) 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 were 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, NLR family pyrin domain-containing protein 3 (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.
【초록키워드】 coronavirus disease, SARS-CoV-2, Respiratory distress syndrome, Coronavirus disease 2019, ACE2, Cytokine storm, coronavirus, pandemic, Biomarker, Mortality, Stress, acute respiratory distress syndrome, body weight, alcohol consumption, alcohol, severe acute respiratory syndrome Coronavirus, angiotensin-converting enzyme 2, Spike protein, Ethanol, proinflammatory, Bronchoalveolar lavage fluid, White blood cell, mice, SARS-CoV-2 spike protein, immune cells, Inflammasome, recruitment, mechanism, Human angiotensin-converting enzyme 2, NF-κB, acute respiratory distress, NLRP3, NLR, Interaction, angiotensin, Immune cell, chronic, blood cell, respiratory distress, protein 3, Alcohol Abuse, STAT3, acute respiratory syndrome, Activation, Factor, subunit, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, therapeutic approaches, enzyme, worsening, syndrome, transgenic mice, lung tissue, human ACE2 receptor, Express, overexpression, dramatic increase, alveolar, decrease, Alveolar space, Course, reported, therapeutic approach, parenchymal, 【제목키워드】 spike, coronavirus 2, respiratory, K18-hACE2, increase,