Abstract 112: Sars-cov-2 Infection Promotes Dyslipidemia And Non-alcoholic Steatohepatitis In Diet-induced Obese Golden Syrian Hamsters

Abstract

Background: Obesity, non-alcoholic steatohepatitis (NASH) and dyslipidemia have been associated with severe forms of COVID-19. To better understand the impact of SARS-CoV-2 infection on dyslipidemia and NASH, we investigated the impact of infection with the beta variant of the SARS-CoV-2 in lean and high fat/cholesterol/fructose diet-induced obese Golden Syrian hamsters. Methods: Lean (chow diet fed) or diet-induced obese hamsters were infected intranasally with the beta variant of the SARS-CoV-2. At baseline (before infection) and at 4-, 7-, 10- and 25-days post-infection (dpi), blood and organs were collected for biochemistry and histology analyses. Results: Early after SARS-CoV-2 infection, lung viral load and pulmonary inflammation were not different between lean and obese hamsters. However, compared to lean hamsters, obese hamsters showed significantly higher MCP-1 serum levels at baseline and after infection, had impaired recovery (lower resolution of lung lesions at 10 dpi, lower body weight regain at 25 dpi), and exhibited higher pulmonary fibrosis at 25 dpi. In both lean and obese hamsters, SARS-CoV-2 infection led to reduction in serum triglycerides and HDL-cholesterol levels at 4 and 7 dpi. However, obese hamsters remained hypertriglyceridemic and hypercholesterolemic, while SARS-CoV-2 infection led to significant elevation of serum free fatty acids and LDL-cholesterol levels at 4 and 7 dpi in those obese individuals, as compared to baseline levels. Despite the substantial weight loss induced by SARS-CoV-2 infection, the NASH phenotype of obese hamsters was maintained, with significantly higher liver steatosis, inflammation, hepatocyte ballooning and fibrosis scores from day 0 to 25 dpi. Additionally, obese hamsters showed significantly higher liver fibrosis at 25 dpi, as compared to lean hamsters. Conclusion: Our data indicate that SARS-CoV-2 infection promotes dyslipidemia and non-alcoholic steatohepatitis in diet-induced obese Golden Syrian hamsters. This model will be useful to investigate the mechanisms leading to severe forms of COVID-19 seen in obese patients with dyslipidemia and NASH.