Is the post-COVID-19 syndrome a severe impairment of acetylcholine-orchestrated neuromodulation that responds to nicotine administration?

Mij

Mij

Senior Member (Voting Rights)
Marco Leitzke, 2023

Abstract
Following a SARS-CoV-2 infection, many individuals suffer from post-COVID-19 syndrome. It makes them unable to proceed with common everyday activities due to weakness, memory lapses, pain, dyspnea and other unspecific physical complaints.

Several investigators could demonstrate that the SARS-CoV-2 related spike glycoprotein (SGP) attaches not only to ACE-2 receptors but also shows DNA sections highly affine to nicotinic acetylcholine receptors (nAChRs). The nAChR is the principal structure of cholinergic neuromodulation and is responsible for coordinated neuronal network interaction. Non-intrinsic viral nAChR attachment compromises integrative interneuronal communication substantially. This explains the cognitive, neuromuscular and mood impairment, as well as the vegetative symptoms, characterizing post-COVID-19 syndrome. The agonist ligand nicotine shows an up to 30-fold higher affinity to nACHRs than acetylcholine (ACh).

We therefore hypothesize that this molecule could displace the virus from nAChR attachment and pave the way for unimpaired cholinergic signal transmission. Treating several individuals suffering from post-COVID-19 syndrome with a nicotine patch application, we witnessed improvements ranging from immediate and substantial to complete remission in a matter of days.

https://bioelecmed.biomedcentral.com/articles/10.1186/s42234-023-00104-7
 
See also: An experimental test of the nicotinic hypothesis of COVID-19 (2022)

Abstract
The pathophysiological mechanisms underlying the constellation of symptoms that characterize COVID-19 are only incompletely understood. In an effort to fill these gaps, a “nicotinic hypothesis,” which posits that nicotinic acetylcholine receptors (AChRs) act as additional severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) receptors, has recently been put forth. A key feature of the proposal (with potential clinical ramifications) is the suggested competition between the virus’ spike protein and small-molecule cholinergic ligands for the receptor’s orthosteric binding sites. This notion is reminiscent of the well-established role of the muscle AChR during rabies virus infection.
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To address this hypothesis directly, we performed equilibrium- type ligand-binding competition assays using the homomeric human α7-AChR (expressed on intact cells) as the receptor, and radio-labeled α-bungarotoxin (α-BgTx) as the orthosteric-site competing ligand. We tested different SARS-CoV-2 spike protein peptides, the S1 domain, and the entire S1–S2 ectodomain, and found that none of them appreciably outcompete [125I]-α-BgTx in a specific manner. Furthermore, patch-clamp recordings showed no clear effect of the S1 domain on α7-AChR– mediated currents. We conclude that the binding of the SARS-CoV-2 spike protein to the human α7-AChR’s orthosteric sites—and thus, its competition with ACh, choline, or nicotine—is unlikely to be a relevant aspect of this complex disease.
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I also googled around and found some reports on social media (Reddit) from people who had tried this under broadly similar circumstances to the four case reports in this thread's article. (I'll just leave links rather than re-quoting their comments.)

First link is from 3 months ago. They reported 7 days ago to have had only modest improvement.

Another was planning and recently reported back a very poor response one week post.
 
This is the author's Twitter, literally it is just a collection of retweets of happy recoveries and rapid improvements, and it reminds me a bit of an LP account. If nicotine patches really give you significant rapid improvement, they should do a trial, it shouldn't be a social media thing.

https://twitter.com/LeitzkeMarco

Also the videos on his FB profile sound more like advertisements for the therapy: https://www.facebook.com/profile.php?id=100091249983747

It seems to be popular with certain covid long haulers.

The fact I know about this is that people in my group every once in a while DM me to recommend me these "promising" therapies that somehow only thrive in social media.

And the above study is literally just a case series of 4 people, no control group, no blinding, literally they just rated their symptoms on a scale of 0-5.

Again, if this works so well, he should do an actual trial.
 
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