Evaluation of High-Throughput Measurements of Persistent SARS-CoV-2 in the Occurrence of Various PASC Phenotypes

Introduction: Multiple studies have now demonstrated that SARS-CoV-2 proteins and/or genetic material persist well beyond the acute phase of COVID-19 in some individuals. Although anatomic persistence of SARS-CoV-2 is indisputable, the clinical relevance is unclear. As such, there is now an urgent need to understand whether SARS-CoV-2 persistence is responsible for at least some post-acute sequelae of SARS-CoV-2 (PASC).

Objective: The primary objective of this study is to evaluate the causal role of persistent antigenemia in the occurrence of PASC.

Methods: In Aim 1, through comparison of well-defined PASC cases with consistently asymptomatic participants in a series of well-powered case-control designs, we will evaluate the relationship between plasma SARS-CoV-2 antigenemia, measured using high-throughput single-molecule array (Simoa®) assays, and each of the PASC clinical phenotypes. In Aim 2, we will add measurements of plasma SARS-CoV-2 RNA (by ultrasensitive PCR) as well as biosensors of SARS-CoV-2 in the form of plasma SARS-CoV-2-specific antibodies and circulating CD4+ and CD8+ T cells. We will also explore the role of circulating NK cells as a biosensor of SARS-CoV-2 and plasma cell-free host RNA as a marker of viral-induced tissue damage. In Aim 3, we will develop and evaluate a more sensitive assay (MOSAIC) to detect whether SARS-CoV-2 antigenemia is present in those with PASC who are undetectable on Simoa®.

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
• Clinical assessment and pathogenesis of clinical manifestations
• Long COVID and other chronic conditions
• Long-term follow-up of the RECOVER Cohorts
• Remaining gaps in tissue-specific manifestations of Long COVID
• Validation of published studies on potential mechanisms of Long COVID using data and biospecimens from RECOVER cohorts
• Viral persistence/reactivation