Download This PaperA Pharmacological Interactome between COVID-19 Patient Samples and Human Sensory Neurons Reveals Potential Drivers of Neurogenic Pulmonary Dysfunction
24 Pages Posted: 4 May 2020
Date Written: April 21, 2020
Abstract
The SARS-CoV-2 virus infects cells of the airway and lungs in humans causing the disease COVID-19. This disease is characterized by cough, shortness of breath, and in severe cases causes pneumonia and acute respiratory distress syndrome (ARDS) which can be fatal. Bronchial alveolar lavage fluid (BALF) and plasma from mild and severe cases of COVID-19 have been profiled using protein measurements and bulk and single cell RNA sequencing. Onset of pneumonia and ARDS can be rapid in COVID-19, suggesting a potential neuronal involvement in pathology and mortality. We sought to quantify how immune cells might interact with sensory innervation of the lung in COVID-19 using published data from patients, existing RNA sequencing datasets from human dorsal root ganglion neurons and other sources, and a genome-wide ligand-receptor pair database curated for pharmacological interactions relevant for neuro-immune interactions. Our findings reveal a landscape of ligand-receptor interactions in the lung caused by SARS-CoV-2 viral infection and point to potential interventions to reduce the burden of neurogenic inflammation in COVID-19 disease. In particular, our work highlights opportunities for clinical trials with existing or under-development rheumatoid arthritis and other (e.g. CCL2, CCR5 or EGFR inhibitors) drugs to treat high risk or severe COVID-19 cases.
Note: Funding: This work was supported by NIH grant NS065926 and NS115441 to TJP.
Conflict of Interest: The authors declare no conflict of interest, except TJP who is a co-founder and board member of 4E Therapeutics.
Ethical Approval: IRB approval for RNA sequencing from human DRG samples was provided by University of Texas at Dallas as described previously (North et al., 2019). Other datasets used here were based on analysis from datasets described in published studies from other groups.
Keywords: COVID-19, neuroimmunology, pulmonary immunology, respiratory neurobiology, ligand receptor signalling, interactome prediction
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