期刊
SIGNAL TRANSDUCTION AND TARGETED THERAPY
卷 6, 期 1, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41392-021-00851-6
关键词
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资金
- National Natural Science Foundation Regional Innovation and Development [U19A2003]
- National Major Scientific and Technological Special Project for Significant New Drugs Development [2018ZX09733001]
- Excellent Youth Foundation of Sichuan Scientific Committee Grant in China [2019JDJQ008]
- Development Program of China [2016YFA0201402]
The study established a mouse model for SARS-CoV-2-induced ARDS in a standard laboratory setting, capturing multiple characteristics of ARDS observed in humans. Therapeutic strategies such as dexamethasone or passive antibody therapy were shown to effectively ameliorate the disease progression in this model. This model may serve as a robust tool for researchers to investigate the pathological mechanisms and develop new therapeutic strategies for COVID-19 and ARDS.
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-1 beta, TNF-alpha, 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.
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