Long COVID – a critical disruption of cholinergic neurotransmission?

Abstract

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Background Following the COVID-19 pandemic, there are many chronically ill Long COVID (LC) patients with difer‑ ent symptoms of varying degrees of severity. The pathological pathways of LC remain unclear until recently and make identifcation of path mechanisms and exploration of therapeutic options an urgent challenge. There is an apparent relationship between LC symptoms and impaired cholinergic neurotransmission. Methods This paper reviews the current literature on the efects of blocked nicotinic acetylcholine receptors (nAChRs) on the main afected organ and cell systems and contrasts this with the unblocking efects of the alkaloid nicotine. In addition, mechanisms are presented that could explain the previously unexplained phenomenon of postvaccination syndrome (PVS). The fact that not only SARS-CoV-2 but numerous other viruses can bind to nAChRs is discussed under the assumption that numerous other post-viral diseases and autoimmune diseases (ADs) may also be due to impaired cholinergic transmission. We also present a case report that demonstrates changes in cho‑ linergic transmission, specifcally, the availability of α4β2 nAChRs by using (-)-[ 18F]Flubatine whole-body positron emission tomography (PET) imaging of cholinergic dysfunction in a LC patient along with a signifcant neurological improvement before and after low-dose transcutaneous nicotine (LDTN) administration. Lastly, a descriptive analysis and evaluation were conducted on the results of a survey involving 231 users of LDTN. Results A substantial body of research has emerged that ofers a compelling explanation for the phenomenon of LC, suggesting that it can be plausibly explained because of impaired nAChR function in the human body. Following a ten-day course of transcutaneous nicotine administration, no enduring neuropathological manifestations were observed in the patient. This observation was accompanied by a signifcant increase in the number of free ligand binding sites (LBS) of nAChRs, as determined by (-)-[ 18F]Flubatine PET imaging. The analysis of the survey shows that the majority of patients (73.5%) report a signifcant improvement in the symptoms of their LC/MEF/CFS disease as a result of LDTN. Conclusions In conclusion, based on current knowledge, LDTN appears to be a promising and safe procedure to relieve LC symptoms with no expected long-term harm.