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. 2021 Feb 8:11:595342.
doi: 10.3389/fimmu.2020.595342. eCollection 2020.

Activation of the Cholinergic Anti-Inflammatory Pathway as a Novel Therapeutic Strategy for COVID-19

Zhen Qin  1   2 , Kefa Xiang  1 , Ding-Feng Su  1 , Yang Sun  1 , Xia Liu  1
Affiliations

Activation of the Cholinergic Anti-Inflammatory Pathway as a Novel Therapeutic Strategy for COVID-19

Zhen Qin et al. Front Immunol. .

Abstract

The outbreak of coronavirus disease 2019 (COVID-19) underlined the urgent need for alleviating cytokine storm. We propose here that activating the cholinergic anti-inflammatory pathway (CAP) is a potential therapeutic strategy. However, there is currently no approved drugs targeting the regulatory pathway. It is evident that nicotine, anisodamine and some herb medicine, activate the CAP and exert anti-inflammation action in vitro and in vivo. As the vagus nerve affects both inflammation and specific immune response, we propose that vagus nerve stimulation by invasive or non-invasive devices and acupuncture at ST36, PC6, or GV20, are also feasible approaches to activate the CAP and control COVID-19. It is worth to investigate the efficacy and safety of the strategy in patients with COVID-19.

Keywords: cholinergic anti-inflammatory pathway; coronavirus disease 2019; cytokine storm; therapeutic strategy; vagus nerve stimulation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Graphical Abstract
Graphical Abstract
Proposed approaches of activating cholinergic anti-inflammatory pathway. (A) Pharmacological activation: Nicotine, anisodamine, and some Chinese herbs could direct or indirectly exert pharmacological activation of α7nAChR. (B) Physical activation: vagus nerve stimulation, such as invasive or non-invasive VNS device shown in Figure 1 , increases the activity of cholinergic anti-inflammatory pathway. (C) Physical activation: some acupuncture points increase the activity of cholinergic anti-inflammatory pathway by activating the afferent vagal. Zu San Li (ST36) is located four finger widths down from the bottom of knee cap, along the outer boundary of shin bone. Nei Guan (PC6) is located three finger breadths below the wrist on the inner forearm in between the two tendons. Feishu (BL13) is on the back, 5 cm lateral to the lower border of the spinous process of the 3rd thoracic vertebra. Baihui (GV20) is on the center of the top of the head where the line connecting the high points of ears crosses the body midline.
Figure 1
Figure 1
mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CHRNA7 Gene (https://www.genecards.org/cgi-bin/carddisp.pl?gene=CHRNA7&keywords=7nAChR).
Figure 2
Figure 2
The device of vagus nerve stimulation. (A) The first device for vagus nerve stimulation (VNS), a pulse generator is placed in a subcutaneous pocket in the left chest wall and a spiral electrode wrapped around the left vagus nerve in the neck (97). (B) GammaCore, a handheld, self-contained non-invasive VNS (nVNS) device, directly contacts cervical skin surfaces and delivers electrical signal to the vagus (98). (C) NEMOS, an external device that provides transcutaneous VNS (tVNS) by using a dedicated intra-auricular electrode, stimulates the auricular branch of the vagus nerve (99).
See this image and copyright information in PMC

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