The increase of the inflammatory markers CRP and Il-6 predict the unfavorable course of the covid-19 infection. (1) (2) The decrease of HRV by more than 40% precedes a 50% increase in CRP during the next 72 hours according to a small study. (3) The sudden decrease of HRV may signal the weakening or collapse of the cholinergic anti-inflammatory pathway. It is supposed that by strengthening this pathway the cytokine storm could be prevented or at least mitigated. (4)(5)(6) In an animal study it was shown that increased vagus nerve activity, measured by (RMSSD), the parasympathetic part of the HRV, the brain inflammatory processes, and the resulting brain damages can be mitigated. (7) This is highly significant, because – besides the cytokines – the spike protein of covid-19 can cross the blood-brain barrier and induce inflammatory processes in the brain leading to neuroinflammation and neurological disorders. (8) (9) (10) Elderly patients with chronic diseases have impaired vagus nerve activity that may exacerbate the covid-19 disease course. (11) For this reason, methods increasing the vagal tone may be beneficial for the treatment or prevention of the severe consequences of covid-19 infection. One of the most promising methods is the intranasal administration of proinsulin c peptide. Systemic administration of C can increase the vagus nerve activity according to clinical trials on insulin-dependent diabetes mellitus patients, that are among the most affected people regarding the mortality of covid-19 caused disease. (12) (13) Proinsulin c peptide administered directly into the brain seems to have even a more pronounced effect on the parasympathetic nervous system. (14) Intranasal application of proinsulin c peptide is effectively transferring the peptide into the brain. (15)
The resident immune cells in the CNS, the microglia, are often activated in patients severely affected by the disease according to autopsic investigations. (16) The hyperactivity of the molecular scissor, cofilin, that regulates the shape and dynamical change of the actin cytoskeleton is responsible for the overactivation of microglia. The reduction of the hyperactivity of the cofilin is leading to the cessation of the overactivity of microglia. (17)(18) Interestingly, proinsulin c peptide, besides increasing HRV, is also able to inactivate cofilin in lymphocytes that may serve as a model for microglia and neurons also. (19)
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