SARS-CoV-2 Neuroimmune Vascular Reservoirs in PASC

Introduction: Persistent cardiovascular (CV) symptoms and heightened CV risk are noted in Post-Acute Sequelae of SARS-CoV-2 (PASC), but the underlying mechanisms remain unclear. Prior research demonstrated SARS-CoV-2 viral RNA (vRNA) and replication within macrophages in coronary vessels of COVID-19 patients. Increased viral entry was observed in cholesterol-loaded macrophages, correlated with neuropilin-1 (NRP-1) and associated with impaired type I interferon responses and lysosomal degradation.

Objective: The project aims to identify cellular and neuroimmune vascular SARS-CoV-2 reservoirs in human tissues and their roles in PASC-related pathology by assessing varying atherosclerosis degrees and correlating viral persistence in neuro vascular tissues with immune changes.

Methods: The study employs a multifaceted approach to investigate SARS-CoV-2 reservoirs in vascular tissues associated with PASC. Autopsy samples from the RECOVER cohort, including aortic and coronary tissues, are analyzed using deep RNA sequencing (dRNAseq), RNAscope, and imaging mass cytometry (IMC). dRNAseq enables comprehensive identification of viral RNA and associated gene expressions, while RNAscope allows for precise localization of SARS-CoV-2 within specific cell types, such as macrophages. IMC provides spatial analysis of protein expressions, facilitating a detailed understanding of immune cell interactions with the virus. The findings are integrated with clinical data, including Electronic Health Records and RECOVER questionnaires, to explore the clinical implications of viral persistence and its role in chronic inflammation and cardiovascular complications in PASC.

Results: Pending.

Conclusion/Discussion: Pending.

Key Topics:

• Chronic immune dysfunction
• Remaining gaps in tissue-specific manifestations of Long COVID
• Viral persistence/reactivation