Integrated Virus and Host Mechanisms of PASC

Introduction: Prior studies of post-acute sequelae of SARS-CoV-2 (PASC) pathogenesis have typically been limited by small sample sizes as well as often a narrow focus that may not fully capture the complexity of PASC pathogenesis.

Objective: We propose a collaborative strategy that will bring together cross-disciplinary investigators from different fields to elucidate PASC pathogenesis from an integrated mechanistic perspective.

Methods: We are testing the mechanistic hypothesis for PASC pathogenesis: that SARS-CoV-2 leads to reduced levels of SPMs that facilitate viral persistence, and both lead to chronic inflammation that contributes to PASC. To investigate this hypothesis, we propose the following Specific Aims: Specific Aim 1: To evaluate persistent virus, SPMs, and chronic inflammation in PASC patients Specific Aim 2: To perform integrated analyses to define correlates of PASC disease and recovery.

Results: Pending.

Conclusion/Discussion: Pending.

Key Topics:

• Assay and in vitro studies to gain mechanistic insights
• Biomarker, in-depth phenotyping assays and in vitro studies using tissue and other biospecimens
• Chronic immune dysfunction
• Collaborative and systems biology approaches