COVID-19: Targeting the cytokine storm via cholinergic anti-inflammatory (Pyridostigmine)

Abstract

Background: The development of COVID-19 having been set apart as the third presentation of an exceptionally pathogenic coronavirus into the human populace after the extreme intense SARS-COV and MERS-COV in the twenty-first century. The infection itself doesn’t make a crucial commitment to mortality, anyway “cytokine storm” created by the unreasonable invulnerable reaction activated by the virus can result in a hyperinflammatory response of lung tissues and deadly lung injury, and in this way increment death rate. In this manner, immunomodulatory medications ought to likewise be remembered for treatment of COVID-19.

Presentation of the hypothesis: the virus particles invade the respiratory mucosa firstly and infect other cells, triggering a series of immune responses and the production of cytokine storm in the body, which may be associated with the critical condition of COVID-19 patients. Once a cytokine storm is formed, the immune system may not be able to kill the virus, but it will certainly kill many normal cells in the lung, which will seriously damage the of lung function. Patients will have respiratory failure until they die of hypoxia. It is not yet clear what the death rate of Covid-19 will be, though the best estimate right now is that it is around 1 percent, 10 times more lethal than seasonal flu due to cytokines storm which trigger a violent attack by the immune system to the body, cause acute respiratory distress syndrome (ARDS) and multiple organ failure, and finally lead to death in severe cases of COVID-19 infection. Therefore, inhibiting cytokine storm can significantly reduce inflammatory injury in lung tissues.

Pyridostigmine (PDG), cholinergic anti-inflammatory pathway (CAP) is a neural mechanism that modulates inflammation through the release of acetylcholine (ACh), resulting in decreased synthesis of inflammatory cytokines such as TNF-α and IL-1. This finding emphasis, the nervous and immune systems work collaboratively during infection and inflammation.

Implications of the hypothesis: Administrations of Pyridostigmine (PDG) as cholinergic agonist inhibits the inflammatory response and lower the mortality of COVID-19 patients. Likewise, activation of the CAP during systemic inflammation down-regulates the production and release of inflammatory cytokines.