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

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

doi:10.1002/ame2.12155

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

Animal Model Exp Med. 2021 Mar 6;4(1):2-15. doi: 10.1002/ame2.12155. eCollection 2021 Mar.

Authors

Yuanwu Ma^{1

2}, Dan Lu^{1

2}, Linlin Bao^{1

2}, Yajin Qu^{1

2}, Jiangning Liu^{1

2}, Xiaolong Qi^{1

2}, Lei Yu^{1

2}, Xu Zhang^{1

2}, Feifei Qi^{1

2}, Qi Lv^{1

2}, Yunpeng Liu^{1

2}, Xudong Shi^{1

2}, Caixian Sun^{1

2}, Jing Li^{1

2}, Jie Wang^{1

2}, Yunlin Han^{1

2}, Kai Gao^{1

2}, Wei Dong^{1

2}, Ning Liu^{1

2}, Shan Gao^{1

2}, Jing Xue^{1

2}, Qiang Wei^{1

2}, Sidan Pan^{1

2}, Hong Gao^{1

2}, Lianfeng Zhang^{1

2}, Chuan Qin^{1

2}

Affiliations

¹ Key Laboratory of Human Disease Comparative Medicine National Health Commission of China (NHC) Institute of Laboratory Animal Science Peking Union Medicine College Chinese Academy of Medical Sciences Beijing China.
² Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases Institute of Laboratory Animal Science Peking Union Medicine College Chinese Academy of Medical Sciences Beijing China.

Abstract

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.

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.

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.

Keywords: COVID‐19; Cardiovascular disease; SARS‐CoV‐2; diabetes mellitus; mouse model.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
COVID-19 / complications*
COVID-19 / physiopathology*
Cardiovascular Diseases / complications*
Cardiovascular Diseases / physiopathology*
Comorbidity
Diabetes Complications / physiopathology*
Diabetes Mellitus
Disease Models, Animal
Male
Mice
SARS-CoV-2