Aggravated pneumonia and diabetes in SARS-CoV-2 infected diabetic mice

ABSTRACT

Multiple clinical and epidemiological studies have shown an interconnection between coronavirus disease 2019 (COVID-19) and diabetes, but experimental evidence is still lacking. Understanding the interplay between them is important because of the global health burden of COVID-19 and diabetes. We found that C57BL/6J mice were susceptible to the alpha strain of SARS-CoV-2. Moreover, diabetic C57BL/6J mice with leptin receptor gene deficiency (db/db mice) showed a higher viral load in the throat and lung and slower virus clearance in the throat after infection than C57BL/6J mice. Histological and multifactor analysis revealed more advanced pulmonary injury and serum inflammation in SARS-CoV-2 infected diabetic mice. Moreover, SARS-CoV-2 infected diabetic mice exhibited more severe insulin resistance and islet cell loss than uninfected diabetic mice. By RNA sequencing analysis, we found that diabetes may reduce the collagen level, suppress the immune response and aggravate inflammation in the lung after infection, which may account for the greater susceptibility of diabetic mice and their more severe lung damage after infection. In summary, we successfully established a SARS-CoV-2 infected diabetic mice model and demonstrated that diabetes and COVID-19 were risk factors for one another.

KEYWORDS:

• SARS-CoV-2
• diabetes
• risk factor
• mice model
• pneumonia

Acknowledgements

We appreciate the services of all staff at the National Kunming High-level Biosafety Primate Research Center. The authors would like thank Institute of laboratory animal sciences CAMS&PUMC, Guangdong CDC, Chongqing CDC and professor Wenjie Tan of China CDC for their help.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability

All study data are included in the article and/or supplementary material. The original data of RNA sequencing in this study is available at NCBI SRA under the accession number PRJNA929576.

Additional information

Funding

This study was supported by the National Key R&D Program of China [2021YFC230170402, 2021YFC0864600, 2020YFA0707602], CAMS Innovation Fund for Medical Sciences [2021-I2M-1-038], Key R&D Program of Yunnan Province [202103AQ100001], the Foundation for Innovative Research Groups of the National Natural Science Foundation of China [82221004].