Impact of SARS-CoV-2 infection on the heart in obese and aged hamsters – COVID-Heart

The objective of the COVID-HEART project is to understand the pathophysiological mechanisms of long-term cardiometabolic complications in SARS-CoV-2 infection, aiming to identify predictive markers of these complications in COVID-19 patients.
This project is related to the general thematic “Physiopathogénie et épidémiologie” and more precisely to “New preclinical research models to validate innovative therapeutic approaches” (the project is based on the use of a new experimental model of SARS-CoV-2 infection in obese and old hamsters) and to “Mid- and long-term consequences of COVID-19 in infected patients” (the project will evaluate the consequences of SARS-CoV-2 infection on the heart at different times post-infection).
We will use an experimental model of infection in the hamster that allows longitudinal monitoring of the infection; it allows the collection of cardiac biopsies, pericardial adipose tissue and blood samples at different times after infection. This preclinical model is well-established and was found to mimic most of the clinical and pathological features of COVID-19. Thus, this model will be instrumental to validate innovative and effective therapeutic approaches after having characterized the cardiac impact of SARS-CoV-2 infection.
There will be 3 groups, lean young adult hamsters, obese young adult hamsters (high-fat/high-sugar diet-induced obesity model), and aged hamsters (>21 months). The last two groups represent the classes of patients most at risk of long-term sequelae from COVID-19, including cardiac ones.
The COVID-HEART project is divided into 3 workpackages (WP). The WP1 is dedicated to the molecular phenotyping of the heart and pericardial adipose tissues by histology, immunohistochemistry, gene expression analyses by RT-qPCR, and analyses of proteins involved in inflammation, oxidative stress, mitochondrial metabolism and autophagy by western blot. The WP2 is dedicated to the analysis of Clusterin, Renin-Angiotensin- System components and new targets of SARS-CoV-2 infection-induced severe cardiac outcomes by microarray. The WP3 is dedicated to deciphering markers for the early prediction of severe cardiac outcomes by using system biology analysis of the targets identified to be modulated in the heart following SARS-CoV-2 infection, by quantifying in blood samples the targets selected from the hamster cardiac biopsies and by validating the data using cardiac biopsies and associated blood samples obtained from patients died from COVID-19, who belong to the "LICORNE" cohort.
The aims of the COVID-HEART project are: 1) to demonstrate that the preclinical model of SARS-CoV-2 infection in hamsters is useful to validate innovative and effective therapeutic approaches after having characterized the cardiac impact of SARS-CoV-2 infection, and 2) to identify markers predictive of severe cardiac outcomes following SARS-CoV-2 infection, notably in the most vulnerable populations of obese and aged individuals.