Inflammatory reflex disruption in COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in Wuhan, China, in late 2019 and caused coronavirus disease 2019 (COVID-19), which is still a global pandemic. In most infected people, SARS-CoV-2 only causes moderate symptoms, whereas in other patients, it leads to severe illness and eventually death. Although the main clinical manifestation of COVID-19 is often seen in the lungs, this disease affects almost all body organs. The excessive and prolonged release of inflammatory cytokines that might occur in COVID-19 patients, known as cytokine storms, stimulates undesired immune responses and can cause various tissues damage. In the current review article, we focus on the potential advantages of the intrinsic cholinergic anti-inflammatory pathway as the efferent arm of the inflammatory reflex in COVID-19 management. Considering this endogenous protective mechanism against chronic inflammation, we focused on the effects of SARS-CoV-2 in the destruction of this anti-inflammatory system. Several studies showed the interaction of SARS-CoV-2 with the alpha-7 subtype of the nicotinic acetylcholine receptor as the effector molecule of the inflammatory reflex. In contrast, neurological manifestations have increasingly been identified as significant extrapulmonary manifestations of COVID-19. The rational connection between these findings and COVID-19 pathogenesis might be an important issue in both our understanding of and dealing with this disease. COVID-19 is deeply rooted in our daily life and requires an urgent need for the establishment of effective therapeutic options, and all the possible treatments must be considered for the control of such inflammatory conditions.