Leitzke Marco, Roach Donald Troy, Hesse Swen, Schönknecht Peter, Becker Georg-Alexander, Rullmann Michael, Sattler Bernhardt, Sabri Osama
Department of Nuclear Medicine, University of Leipzig Medical Centre, Leipzig, 04103, Germany.
Department of Anesthesiology, Intensive Care Medicine, Pain- and Palliative Therapy Helios Clinics, Colditzer Straße 48, Leisnig, 04703, Germany.
Bioelectron Med. 2025 Feb 27;11(1):5. doi: 10.1186/s42234-025-00167-8.
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 and make identification of path mechanisms and exploration of therapeutic options an urgent challenge. There is an apparent relationship between LC symptoms and impaired cholinergic neurotransmission.
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 (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 cholinergic transmission, specifically, the availability of α4β2 nAChRs by using (-)-[F]Flubatine whole-body positron emission tomography (PET) imaging of cholinergic dysfunction in a LC patient along with a significant 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.
A substantial body of research has emerged that offers 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 significant increase in the number of free ligand binding sites (LBS) of nAChRs, as determined by (-)-[F]Flubatine PET imaging. The analysis of the survey shows that the majority of patients (73.5%) report a significant improvement in the symptoms of their LC/MEF/CFS disease as a result of LDTN.
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.
在新冠疫情之后，出现了许多患有不同严重程度症状的慢性新冠后遗症（LC）患者。直到最近，LC的病理途径仍不清楚，这使得确定病理机制和探索治疗方案成为一项紧迫的挑战。LC症状与胆碱能神经传递受损之间存在明显关联。
本文回顾了当前关于阻断烟碱型乙酰胆碱受体（nAChRs）对主要受影响器官和细胞系统影响的文献，并将其与生物碱尼古丁的解封作用进行对比。此外，还阐述了一些机制，这些机制可以解释此前无法解释的疫苗接种后综合征（PVS）现象。在假设许多其他病毒感染后疾病和自身免疫性疾病（ADs）也可能归因于胆碱能传递受损的前提下，讨论了不仅严重急性呼吸综合征冠状病毒2（SARS-CoV-2），而且许多其他病毒都能与nAChRs结合这一事实。我们还展示了一个病例报告，该报告通过对一名LC患者进行低剂量经皮尼古丁（LDTN）给药前后的胆碱能功能障碍进行（-）-[F]氟比汀全身正电子发射断层扫描（PET）成像，证明了胆碱能传递的变化，具体而言，即α4β2 nAChRs的可用性变化，同时该患者的神经功能有显著改善。最后，对一项涉及231名LDTN使用者的调查结果进行了描述性分析和评估。
大量研究涌现出来，为LC现象提供了令人信服的解释，表明它可以合理地解释为人体中nAChR功能受损。在患者接受为期十天的经皮尼古丁给药疗程后，未观察到持久的神经病理表现。通过（-）-[F]氟比汀PET成像确定，这一观察结果伴随着nAChRs的游离配体结合位点（LBS）数量显著增加。调查分析表明，大多数患者（73.5%）报告称，LDTN使他们的LC/肌痛性脑脊髓炎/慢性疲劳综合征（MEF/CFS）疾病症状有显著改善。
总之，基于目前的知识，LDTN似乎是一种有前景且安全的缓解LC症状的方法，预计不会有长期危害。
