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)

Smith College

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

Upregulation of Pulmonary Immune Cell-Derived Receptors from SARS-CoV-2 Infection.

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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