SARS-CoV-2 infection aggravates chronic comorbidities of cardiovascular diseases and diabetes in mice

SARS-CoV-2 感染加重小鼠心血管疾病和糖尿病的慢性合并症

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作者:Yuanwu Ma, Dan Lu, Linlin Bao, Yajin Qu, Jiangning Liu, Xiaolong Qi, Lei Yu, Xu Zhang, Feifei Qi, Qi Lv, Yunpeng Liu, Xudong Shi, Caixian Sun, Jing Li, Jie Wang, Yunlin Han, Kai Gao, Wei Dong, Ning Liu, Shan Gao, Jing Xue, Qiang Wei, Sidan Pan, Hong Gao, Lianfeng Zhang, Chuan Qin

Background

Cardiovascular diseases (CVDs) and diabetes mellitus (DM) are top two chronic comorbidities that increase the severity and mortality of COVID-19. However, how SARS-CoV-2 alters the progression of chronic diseases remain unclear.

Conclusion

We established mouse models mimicked the complex pathological symptoms of COVID-19 patients with chronic diseases. Pre-existing diseases could impair the inflammatory responses to SARS-CoV-2 infection, which further aggravated the pre-existing diseases. This work provided valuable information to better understand the interplay between the primary diseases and SARS-CoV-2 infection.

Methods

We used adenovirus to deliver h-ACE2 to lung to enable SARS-CoV-2 infection in mice. SARS-CoV-2's impacts on pathogenesis of chronic diseases were studied through histopathological, virologic and molecular biology analysis.

Results

Pre-existing CVDs resulted in viral invasion, ROS elevation and activation of apoptosis pathways contribute myocardial injury during SARS-CoV-2 infection. Viral infection increased fasting blood glucose and reduced insulin response in DM model. Bone mineral density decreased shortly after infection, which associated with impaired PI3K/AKT/mTOR signaling.

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