not-yet-known not-yet-known not-yet-known unknown Background: Following the COVID-19 pandemic, there are many chronically ill Long COVID (LC) patients with different symptoms of varying degrees of severity. The pathological pathways of LC remain unclear until recently. This makes identification 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 effects of blocked nicotinic acetylcholine receptors (nAChRs) on the main affected organ and cell systems and contrasts this with the unblocking effects of the alkaloid nicotine. In addition, mechanisms are presented that could explain the previously unexplained phenomenon of post-vaccination syndrome. 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. A case report presents the (-)-[ 18F]Flubatine whole-body positron emission tomography (PET) imaging of cholinergic dysfunction in a LC patient and the significant neurological improvement before and after low-dose transcutaneous nicotine (LDTN) administration. Results: The literature provides a wealth of evidence that LC is adequately described based on impaired nAChR function in the cells of the human body. After 10 days of transcutaneous nicotine administration, no persistent neuropathology was detected in the patient, which was accompanied by a significant increase in free ligand binding sites (LBS) of nAChRs in (-)-[ 18F]Flubatine PET. Conclusions: In conclusion, based on current knowledge, LDTN appears to be a promising and very safe procedure with no expected long-term harm.