Abstract 15507: The Role of Obesity in Covid-19 Pathogenesis and Inflammation

Abstract

SARS-CoV-2 has caused a global pandemic unseen for nearly a century. To date hundreds of millions of people have been diagnosed and millions more have died from COVID-19 disease; many of which are in groups with comorbidities. Obesity is associated with a 3.07 times higher risk of hospitalization and a 1.42 times higher risk of severe illness. However, our understanding of obesity-accelerated severity of COVID-19 is limited. To model the increased disease severity of obese individuals with COVID-19, we used a humanized ACE2 (hACE2) transgenic mouse model, in which hACE2 is under the cytokeratin-18 promoter (K18). Modeling the effects of obesity on COVID-19 in K18-hACE2 mice will help us better understand the mechanisms underlying obesity-accelerated severity of COVID-19 disease and inflammation. We have developed a study in which K18 hACE2 mice infected with SARS-CoV-2 were fed both a normal standard diet as well as a western high fat and carbohydrate diet that causes them to gain excess weight and become obese over a period of 3 months. K18-hACE2 obese mice lose a signifyingly more percentage body weight over both a 7 (acute) 14 day (long-term) period than normal diet fed mice do after infection with SARS-CoV-2. H&E staining analysis of lung histological changes indicated a dramatic increase in inflammation in our K18 hACE2 obese mice infected with SARS-CoV-2 . Subgenomic qPCR and IHC staining was used to quantify virus (viral titer) which indicated that in both of our diet groups after infection did not have a significantly different SARS-CoV-2 viral load. No significant difference in the SARS-CoV-2 viral load was detected at either 7 or 14 dpi with SARS-CoV-2 . We further measured adipokines with an ELISA on two of the most notable adipokines: leptin and adiponectin. Levels of leptin were significantly higher in our obese K18-hACE2 mice but not in our normal mice after infection. There was no difference however in the levels of adiponectin. Obese K18-hACE2 mice show a more severe COVID 19 phenotype than normal diet mice after infection and can be used to further study the underlying mechanism of how SARS-CoV-2 infection in obese individuals causes a more severe disease phenotype.