Published on 23 August, 2023

There is increasing coverage of the connection between the nAChRs (nicotinic acetylcholine receptors) and the modulation of Long Covid.

Professor Jeanne-Pierre Changeux, Professor of Neuroscience at the Pasteur Institute, who first identified and purified the nicotinic acetylcholine receptor, posed the hypothesis soon after the onset of the Pandemic in April 2020 in “A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications” (i).

This was followed by further peer-reviewed studies such as “A potential interaction between the SARS-CoV-2 spike protein and nicotinic acetylcholine receptors” and “The SARS-CoV-2 Virus and the Cholinergic System: Spike Protein Interaction with Human Nicotinic Acetylcholine Receptors and the Nicotinic Agonist Varenicline” (ii).

It appears that the SARS-CoV-2 related spike protein attaches not only to ACE-2 receptors but also to nAChRs.

“The nAChR is responsible for coordinated neuronal network interaction” (iii), and viral attachment to this will “compromise integrative interneuronal communication substantially.” (iv).

Lagoumintzis et al wrote in March 2021 in “Nicotinic cholinergic system and COVID-19”: “Our findings provide further support to the hypothesis about the protective role of nicotine and other cholinergic agonists.” (v).

In their response to the BMJ Editor, K. Farsalinos and K. Poulas suggest that –

“It is, perhaps, timely to propose a clinical trial of pharmaceutical nicotine in COVID-19 patients.”

A recent article by Leitzke from Jan. 2023(iv) now provides further evidence as well as convincing case studies that the agonist ligand nicotine, which has a 30-fold higher affinity to nACHrs than acetylcholine, may be able to displace the spike protein (viral spike glycoprotein — SGP – segments) from nACHR attachment. The cases presented, using a 7.5 mg patch attached for only six days, all “witnessed improvements ranging from immediate and substantial to complete remission in a matter of days.””

It needs pointing out that the UK’s Royal Society for Public Heath noted in 2015 that “nicotine by itself is fairly harmless” (vii), it is the other damaging chemicals it is combined with in cigarettes that make it harmful.

The nicotine was applied trans dermally in patches in the Leitzke studies cited above, removing the dangers of inhalation.

There is also a role for niacin itself as a direct precursor of NAD+(viii). Dr. Wentzel, one of the authors of “COVID-19: NAD+ deficiency may predispose the aged, obese and type2 diabetics to mortality through its effect on SIRT1 activity”,   talks about “Covid-induced secondary Pellagra” and has seen significant improvement from using B3 in its specific niacin form, together with other supplements he mentions (ix).

As the October 2020 Ten Hove article on the role of nicotinic receptors in SARS-CoV-2 explains, “vagus nerve stimulation (VNS) activates nAChRs” (x), so there is latitude for much more to restore health post-Covid than just the previous initiatives outlined.

It has long been suspected that ME/CFS, too, is characterised by disturbance to cholinergic pathways (xi)(xii).

A recent discovery that mitochondria express a range of AChR subtypes, including the nicotinic α3 subunit receptor, suggests that nAChR may impact mitochondrial function directly to regulate oxidative stress. “In the face of dysregulation in several neurotransmitters, including acetylcholine, the mitochondrial stress associated with the activation of these nicotinic receptors would lead to an alteration in intracellular dynamics in several immune cells, including NK cells.” (xiii)

Maybe these same initiatives that are already proving miraculous improvements (in some cases) for Long Covid will also prove useful for ME/CFS.

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You can view this article and others, including our upcoming webinars in our August 2023 Newsletter.

You can also view Professor Lamberts fascinating webinar on Long COVID from a Clinical Perspective and the Presentation Slides.

Click on AONM’s LONG COVID tab to view Dr. Schwarzbach’s webinar on Post-COVID Viral Reactivation: Incidence and Approaches and also the Presentation Slides.

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References:

i. Changeux JP, Amoura Z, Rey FA, Miyara M. A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications. C R Biol. 2020 Jun 5;343(1):33-39.

ii. Carlson EC, Macsai M, Bertrand S, Bertrand D, Nau J. The SARS-CoV-2 Virus and the Cholinergic System: Spike Protein Interaction with Human Nicotinic Acetylcholine Receptors and the Nicotinic Agonist Varenicline. Int J Mol Sci. 2023 Mar 15;24(6):5597

iii. Leitzke M. Is the post-COVID-19 syndrome a severe impairment of acetylcholine– orchestrated neuromodulation that responds to nicotine administration? Bioelectron Med. 2023 Jan 18;9(1):2.

iv. Ibid

v. Lagoumintzis G, Chasapis CT, Alexandris N, Kouretas D, Tzartos S, Eliopoulos E, Farsalinos K, Poulas K. Nicotinic cholinergic system and COVID-19: In silico identification of interactions between α7 nicotinic acetylcholine receptor and the cryptic epitopes of SARS-Co-V and SARS-CoV-2 Spike glycoproteins. Food Chem Toxicol. 2021 Mar;149:112009.

vi. Op. ed.

vii. https://www.rsph.org.uk/about-us/news/nicotine–no-more-harmful-to-health-thancaffeine-.html

viii. Miller R, Wentzel AR, Richards GA. COVID-19: NAD+ deficiency may predispose the aged, obese and type2 diabetics to mortality through its effect on SIRT1 activity. Med Hypotheses. 2020 Nov;144:110044.

ix. https://www.youtube.com/watch?v=C3w7skYHcSg&t=45s

x. Ten Hove AS et al. The role of nicotinic receptors in SARS-CoV-2 receptor ACE2 expression in intestinal epithelia. Bioelectron Med. 2020 Oct 28;6:20.

xi. Lidbury BA, Fisher PR. Biomedical Insights that Inform the Diagnosis of ME/CFS. Diagnostics (Basel). 2020 Feb 8;10(2):92.

xii. https://me-pedia.org/wiki/Acetylcholine

xiii. Cortes Rivera M, Mastronardi C, Silva-Aldana CT, Arcos-Burgos M, Lidbury BA. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Comprehensive Review. Diagnostics (Basel). 2019 Aug 7;9(3):91.