Leveraging RECOVER Infrastructure to Identify the Signatures and Pharmacological Treatments for PASC Respiratory Conditions

Introduction: Respiratory COVID-19 symptoms are the leading cause of both acute morbidity and chronic post-acute sequelae of SARS-CoV-2 (PASC) infection in adults and children.

Objective: Our overall objective is to uncover respiratory PASC signatures via applying cutting-edge single cell technologies to a variety of RECOVER sample types from the Adult and Autopsy cohorts.

Methods: Our global aim is to define, integrate, and compare the pathobiological profiles of RECOVER adult (younger and older) blood and autopsy lung samples using multimodal bulk and single cell technologies. This will be accomplished via three sub-aims. Sub Aim A: To identify age specific PASC immune memory by generating bulk and single nucleus transcriptomic and epigenomic profiles of blood cell types using RECOVER adult samples of various ages. Sub Aim B: To define PASC biomarkers by generating single nucleus transcriptomic and epigenomic profiles of lung using RECOVER autopsy or explanted (validation cohort) samples and compare the signatures with blood. Sub Aim C: To define how lung cellular communities and communications are remodeled in PASC by generating spatial transcriptomic profiles using PASC autopsy or explanted (validation cohort) samples.

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 manifestations of chronic viral infections, biological pathways, immune-autoimmune disorders, systems, organs, or diseases
• Linking autopsy findings with pathobiological mechanisms of Long COVID to guide targeted interventions
• Long COVID and other chronic conditions
• Remaining gaps in tissue-specific manifestations of Long COVID