Project Team

Chiara Giannarelli, MD, PhD, Associate Professor of Medicine Cardiology and Associate Professor of Pathology

Natalia Eberhardt, PhD, Post-Doctoral Fellow who together with Dr. Smyrnis has established the SARS-CoV-2 infection in vitro model and the in ex-vivo vascular explants with atherosclerosis

Panagiotis Smyrnis, MD, Post-Doctoral Fellow and vascular surgery resident

Ravneet Kaur, MS, Bioinformatician with expertise in single cell transcriptome, omics and proteome analysis

Project summary:

Project lead Dr. Chiara Giannarelli

To analyze tissue samples obtained from patients undergoing heart transplants to explore SARS-CoV-2 viral reservoirs in human vasculature (blood vessels), with a focus on elucidating the role of macrophages and foam cells as reservoirs sites. The team will use advanced technologies to identify SARS-CoV-2 in samples and will perform experiments to determine how reservoirs in human vasculature may influence immune responses in both tissue and blood, including their impact on plaque pathology and LongCOVID cardiovascular risk. 

Project background:

COVID-19 is linked to heart disease complications, including acute coronary syndrome, myocardial infarction, and stroke. This heightened risk for atherosclerotic cardiovascular events persists even after the acute phase of the infection has resolved, posing a continued risk of cardiovascular events in COVID-19 survivors. Emerging evidence also indicates that certain individuals with LongCOVID may harbor the virus within their bodies beyond the acute infection phase, establishing a reservoir of replicating virus and/or viral RNA. Persistence of these reservoirs in tissue could lead to the release of viral proteins into the bloodstream. Ir could also lead to a chronic inflammatory state, a key driver of heart disease plaque formation and progression. 

In 2019, New York City and NYU Langone Medical Center were situated at the epicenter of the COVID-19 pandemic. The Center consequently started to meticulously curate a unique biobank of human autopsy samples derived from COVID-19-infected vasculature (blood vessels) and various organs, including lungs. Leveraging these autopsy samples, alongside an ongoing collection of fresh human vascular tissue from patients with and without prior history of COVID-19, the project team recently published a paper showing that SARS-CoV-2 infection triggers pro-atherogenic inflammatory responses in human coronary vessels. The data suggest that that lipid-rich macrophages and vascular cells within atherosclerotic lesions serve as a reservoir for SARS-CoV-2 due to their long life spans and diminished capacity to clear the virus. These vascular reservoirs could trigger sustained low-grade inflammatory responses locally and systemically, which could exacerbate atherosclerosis and contribute to an elevated risk for cardiovascular events in the long term. 

To investigate this, the team will leverage ATHERO-IN and ATHERO-COR: two clinical studies collecting tissue samples from hundreds of patients undergoing vascular surgery and heart transplants, including coronaries, left ventricle tissue, bone marrow, lymph nodes, and peripheral venous blood. Comprehensive patient data including COVID-19 history, vaccination status, Long-COVID symptoms and medications records are also obtained. The project team will analyze collected vascular tissue for SARS-CoV-2 using advanced technologies such as deep RNA sequencing. They will also create models – including a SARS-CoV-2 human vascular explant model to elucidate the impact of the SARS-CoV-2 vascular reservoirs on plaque inflammation. The findings should clarify if antivirals or other therapies can be better leveraged to prevent serious cardiac events in people exposed to SARS-CoV-2.

Featured image: Representative image by the project team of spatial analysis showing the location of CD68 RNA, SARS-CoV-2 S+ or S antisense+ cells and CD68+ SARS-CoV-2 RNA double-positive cells in coronary samples.