Abstract
Severe COVID-19 is characterised by immune dysregulation and a highly inflammatory cytokine storm with symptoms of dysautonomia. It has been proposed that this is at least partially a result of dysregulation of the cholinergic anti-inflammatory pathway and that nicotine may be a useful therapeutic intervention. Post Acute COVID Syndrome (also known as ‘Long COVID’) and Post COVID Vaccination Syndrome are being increasingly recognised and are also characterised by prominent inflammatory markers and dysautonomia. A narrative review of the literature found the actions of the cholinergic system are profoundly anti-inflammatory and act via the α7nACh receptors. The spike protein has been demonstrated to contain an amino acid sequence near the Receptor Binding Domain that has homology with a-1 neurotoxins and is demonstrated in silico to interact with α7nACh, impairing the cholinergic anti-inflammatory system. Nicotine has been proposed as having a possible therapeutic role in mitigating this effect. However, its place is limited due to widespread nicotine actions and significant adverse effects in chronic dosing. Other potential therapeutic interventions addressing background chronic sympathetic nervous system activation and dysautonomia are therefore considered for modulation of the cholinergic system in the management of Post Acute COVID Syndrome/ Post Acute COVID Vaccination Syndrome in the stead of nicotine.