Deciphering the Link Between Severe Acute Respiratory Coronavirus 2 Infection and Long-Term Neurological and Pulmonary Sequelae

Introduction: We will test the hypothesis that SARS-CoV-2 respiratory infection, leads to chronic changes in lung. In addition, acting through the lung-innervating neural circuit, it impacts neuronal activity and neural inflammation.

Objective: We have conducted discovery studies to systematically profile the chronic impact of infection on the brain and the lung.

Methods: We will determine if and how SARS-CoV-2 infection in humanized ACE2 mice leads to chronic changes in neural inflammation and gene expression. We will determine at single cell resolution how SARS-CoV-2 infection of the human lung causes chronic transcriptomic and epigenomic changes.

Results: We have uncovered changes in gene expression, including inflammatory genes in the brain of mice following SARS-CoV-2 infection of the lung. In addition, using Multiome technology, we have profiled the explanted lungs of donors that suffer from SARS-CoV-2 infection induced Long COVID symptoms including fibrosis. We have identified extensive changes in both the transcriptome and the epigenome.

Conclusion/Discussion: We have found the lung fibrosis as a consequence of SARS-CoV-2 share similarities and differences with other traditional pulmonary fibrosis conditions, setting the stage for future functional tests for the mechanisms underlying the differences.

Key Topics:

• Clinical manifestations of chronic viral infections, biological pathways, immune-autoimmune disorders, systems, organs, or diseases
• Collaborative and systems biology approaches
• Comparative studies of Long COVID with other post-viral and post-infectious syndromes
• Long COVID and other chronic conditions