Origins of Post-Acute Sequelae SARS-CoV-2 Infection (PASC) Lung Fibrosis

Introduction: Pulmonary Long COVID is a condition with prolonged respiratory symptoms after COVID infection. Although prior work has shown both radiographic and physiologic abnormalities, the molecular mechanisms driving these changes remain poorly understood.

Objective: The objective of this study was to identify molecular mechanisms underpinning changes in lung fibrosis and lung function.

Methods: Patients with symptoms consistent with pulmonary Long COVID were recruited from UAB cohort. Subjects underwent blood collection and bronchoscopy, along with clinical features of disease such as chest CT imaging, spirometry, and patient related outcomes. Blood and bronchoscopy samples were processed and then assessed for a variety of metrics of inflammation, immune response, oxidative stress, tissue injury, and microbiome. These results will then be integrated with clinical features of disease to better associate with key pulmonary Long COVID phenotypes.

Results: Patient cohort has been fully recruited and procedures have been completed. Preliminary results suggest notable changes in lung metabolomic signatures in patients with CT scan-based lung fibrosis and reduced lung function. These preliminary findings are subject to change pending final analysis and results.

Conclusion/Discussion: Although final results are pending, the current study will use a breadth of data and will provide the first insights into lung-specific mechanisms operative in the development of pulmonary Long Covid. These results could provide new biomarkers for disease progression and possible new therapeutic targets.

Key Topics:

• Biomarker, in-depth phenotyping assays and in vitro studies using tissue and other biospecimens
• Long COVID and other chronic conditions