Inactivated SARS-CoV-2 induces acute respiratory distress syndrome in human ACE2-transgenic mice.
Zhenfei BiWeiqi HongHaiying QueCai HeWenyan RenJingyun YangTianqi LuLi ChenShuai-Yao LuXiao-Zhong PengYanping QianPublished in: Signal transduction and targeted therapy (2021)
The development of animal models for COVID-19 is essential for basic research and drug/vaccine screening. Previously reported COVID-19 animal models need to be established under a high biosafety level condition for the utilization of live SARS-CoV-2, which greatly limits its application in routine research. Here, we generate a mouse model of COVID-19 under a general laboratory condition that captures multiple characteristics of SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) observed in humans. Briefly, human ACE2-transgenic (hACE2) mice were intratracheally instilled with the formaldehyde-inactivated SARS-CoV-2, resulting in a rapid weight loss and detrimental changes in lung structure and function. The pulmonary pathologic changes were characterized by diffuse alveolar damage with pulmonary consolidation, hemorrhage, necrotic debris, and hyaline membrane formation. The production of fatal cytokines (IL-1β, TNF-α, and IL-6) and the infiltration of activated neutrophils, inflammatory monocyte-macrophages, and T cells in the lung were also determined, suggesting the activation of an adaptive immune response. Therapeutic strategies, such as dexamethasone or passive antibody therapy, could effectively ameliorate the disease progression in this model. Therefore, the established mouse model for SARS-CoV-2-induced ARDS in the current study may provide a robust tool for researchers in the standard open laboratory to investigate the pathological mechanisms or develop new therapeutic strategies for COVID-19 and ARDS.
Keyphrases
- sars cov
- acute respiratory distress syndrome
- extracorporeal membrane oxygenation
- mechanical ventilation
- mouse model
- endothelial cells
- respiratory syndrome coronavirus
- high glucose
- immune response
- weight loss
- pulmonary hypertension
- oxidative stress
- drug induced
- diabetic rats
- coronavirus disease
- dendritic cells
- emergency department
- rheumatoid arthritis
- angiotensin ii
- high dose
- roux en y gastric bypass
- induced pluripotent stem cells
- radiation therapy
- adipose tissue
- bariatric surgery
- type diabetes
- minimally invasive
- toll like receptor
- insulin resistance
- pluripotent stem cells
- stem cells
- mesenchymal stem cells
- locally advanced
- low grade
- bone marrow
- skeletal muscle
- metabolic syndrome
- peripheral blood
- weight gain
- high grade
- electronic health record