Defining and Mitigating Mucosal Persistence of SARS-CoV-2 in Individuals with PASC

Introduction: Understanding the inflammatory basis and the potential viral triggers of post-acute sequelae of SARS-CoV-2 infection, or Long COVID, has been a major challenge. Suggestions of SARS-CoV-2 viral reservoirs have been implicated from autopsies, tissue biopsies, and viral proteins in plasma almost a year after the primary infection. Reactivation of latent viruses, such as Epstein Barr Virus (EBV), have also been suggested.

Objective: For this study, we will be testing fresh and frozen samples for media enriched with newly synthesized antibodies (MENSA) preparation and validating these results with additional studies of MENSA with inflammatory plasma responses from additional Long COVID patients.

Methods: Our laboratory has developed a novel assay to capture SARS-CoV-2-specific antibodies from nascent antibody-secreting cells (ASC) that are released into the blood during acute infections in a patented matrix called, MENSA, media enriched with newly synthesized antibodies. MENSA from newly-minted or nascent ASC provides an immune snapshot at the time of illness whereas serum serologies provide the historical record over one's lifetime. We have shown that 60% of the patients with Long COVID have evidence of active immune responses by MENSA to SARS-CoV-2 and herpes viruses, such as EBV.

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
• Clinical assessment and pathogenesis of clinical manifestations
• Clinical manifestations of chronic viral infections, biological pathways, immune-autoimmune disorders, systems, organs, or diseases
• Cross-disciplinary modeling of tissue/organ/system dysfunction caused by other forms of tissue/organ/system injury
• Long COVID and other chronic conditions
• Validation of published studies on potential mechanisms of Long COVID using data and biospecimens from RECOVER cohorts
• Viral persistence/reactivation