Bulk RNA-sequencing of human dorsal root ganglia (hDRG) have revealed ligand expression whose receptors are present in lung immune cells, and whose receptors are upregulated from SARS-CoV-2 infection.
- Ephrin (Eph) ligands
- Epidermal growth factor (EGF) ligands

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Current research lends preliminary support for the hypothesis that sensory neurons innervating the lung have the capacity to modulate the lung's immune response to SARS-CoV-2 infection. 
- Pulmonary immune cell-derived receptors are upregulated following viral infection
- Sensory neurons (hDRGNs) express ligands for the receptors upregulated in lung immune cells

Limitations and caveats of the research are listed as follows:
- there is no transcriptomic data for sensory neurons of COVID-19 patients, and current research relies on an assumption that upregulated immune-cell receptors are responding to sensory-neuron ligands 
- there are no existing animal model studies on neuro-pertubation of immunity
- nociceptor (pain-receptor sensory neurons) directionality on lung immunity is unclear; these sensory afferents have been shown to provide either beneficial or detrimental effects, so neuron promotion or suppression of COVID-19 immunity is unknown
- research is limited to sympathetic nerves (DRGNs), and no conclusions can be drawn regarding parasympathetic nerves (nodose, jugular ganglia)

If lung-innervating sensory neurons signal to immune cells through the release of ligands, this establishes a positive feedback-loop/bidirectional interaction. This hypothesis opens up the possibility of neurogenic-mediated vasodilation, inflammation, pain, and immunity-recruitment.

Signaling: From Sensory Neurons to Pulmonary Immune Cells.

Ray, P. R., Wangzhou, A., Ghneim, N., Yousuf, M. S., Paige, C., Tavares-Ferreira, D., ... & Neerukonda, S. V. (2020). A pharmacological interactome between COVID-19 patient samples and human sensory neurons reveals potential drivers of neurogenic pulmonary dysfunction. Brain, Behavior, and Immunity.  doi:10.1016/j.bbi.2020.05.078. https://reader.elsevier.com/reader/sd/pii/S088915912030670X?token=47BD27DF03A0DC9F9945F6E90A2137EAFCB238A79393A82CA3917F589C6702E1240C841686F05BA6D96293A4B2699299

A pharmacological interactome between COVID-19 patient samples and human sensory neurons reveals potential drivers of neurogenic pulmonary dysfunction

Various genes for immune-cell receptors have shown to be differentially expressed in COVID-19 patient bronchial alveolar lavage fluid (BALF) as compared to control data, receptors of which sensory neurons express ligands for.
- Ephrin (Eph) receptors
- Epidermal growth factor receptor (EGFR)

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