The COVID-19 disease, with its origin in Wuhan China, has caused significant morbidity and mortality across the world. The disease appears to be severe in males, Asian and Afro-Caribbean races; people with diabetes and obese patients. And the cause of death in COVID-19 is a multiorgan failure, presumed to be secondary to an extreme immune response to the SARS-COV-2 virus. Inflammation and the accompanying immune response in severe sepsis is a well-recognised mechanism. However, the return to normal homeostasis via the counter anti-inflammatory pathway appears to be a less well-understood framework. The authors have reviewed the literature and studies conducted over the last few decades on sepsis, inflammation, nicotine and the anti-inflammatory pathway. This article outlines the cholinergic anti-inflammatory pathway (CAP); the role of the vagus nerve; the α7 nicotinic acetylcholine receptor (α7nAChR) and the effects of nicotine as an anti-inflammatory agent. Electrical or mechanical vagus nerve stimulation or α7nAChR agonists stimulate the CAP. In contrast to the traditional parasympathetic nervous system muscarinic receptor; the CAP via the vagus nerve signals through the α7nAChR. Inhibition of the CAP produces a hyper-excited inflammatory response. Controlling cytokine production is critical for preventing unrestrained pathological inflammation, and the α7nAChR is a crucial anti-inflammatory target.