How to survive the coronavirus infection by activating the vagus nerve with the help of central proinsulin c peptide.

A special feature of the coronavirus infection (COVID-19) is that in certain cases it has rapid progression and triggers a so-called cytokine storm attacking vital organs, especially the lungs and the heart. The conventional antibiotic and cortico-steroid treatments usually prove to be ineffective in these cases. Reports claim that in more severely affected patients often the central nervous system is also damaged.[1] Most of the antibiotics, almost routinely applied, may negatively affect the nervous system in such situations.[2] The application of glucocorticoid medication may also be disadvantageous, and its administration is only recommended in exceptional cases in COVID-19 patients. Glucocorticoids may harm the cholinergic anti-inflammatory pathway, a conclusion drawn from the fact that they may unfavorably affect heart-rate variability (HRV).[3] Severely affected COVID-19 patients are usually elderly people, suffering from hypertension, diabetes and cardiovascular problems. In these cases the cholinergic anti-inflammatory pathway is weak and the HRV is often low. In most severe cases the CRP value indicating inflammation is high, which, however, is in inverse correlation with the HRV value.[4] [5]

Inflammation markers are generally negatively correlated with the HRV value. [6]
It is plausible to assume that the fatal consequences of COVID-19, the cytokine storm may be prevented most effectively through treating and reinforcing the cholinergic anti-inflammatory pathway, the vagus nerve.[7] The efficacy of this therapy may be verified through HRV measurements.

The primary cause of fatality from COVID-19 is septic shock. In this case HRV falls below a critical level (SDNN ≤17ms).[8] In an animal model, after resuscitation from a septic shock the activation of the vagus nerve promoted the restauration of healthy organ functions, the vascular barrier strengthened and the mitochondrial function likewise improved.[9]
The appearance of myocarditis has a significant role in 40% of COVID-19 patients with a very poor prognosis. [10] [11] The vagus nerve of these patients weakens, and becomes unable to counteract the inflammation and secure a normal heartrate.

An important fact in this respect is that the HRV values in children suffering from viral myocarditis, already low, further decreases when heart arrhythmia appears indicating the deterioration of their health status as well as declining vagus nerve function. If the activity of the vagus nerve improves, HRV follows suit, and protects against ventricular fibrillation.[12]
The activation of the vagus nerve specifically protects the lungs against inflammation and injuries caused by artificial respiration.[13] [14] The latter information is of particular significance in the light of the fact that in severely affected COVID-19 patients artificial respiration is often needed.

A plausible method of activating the vagus nerve, improving low HRV and restoring the cholinergic anti-inflammatory pathway is the central administration of proinsulin C-peptide, which may have a life-saving effect in critical situations, prevent the cytokine storm, reduce the likelihood of sepsis or pneumonia, myocarditis, heart arrhythmia, ventricular fibrillation or reduce the severity of the pathological progress of these problems. [15] [16]

[1] Mao L. et al.: Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: a retrospective case series study. In: medrxiv: Posted February 25, 2020.

[2] Rezaei,NJ. et al.: Neurotoxicity of the antibiotics:  A comprehensive study. In: Neurology India, 2018:66,6: 1732-1740.

[3] Adlan, AM. et al.: Acute hydrocortisone administration reduces cardiovagal baroreflex sensitivity and heart rate variability in young men. In: The Journal of Physiology, 2018:596,20.

[4] Huang, Y. et al.: Clinical characteristics of 36 non-survivors with COVID-19 in Wuhan, China. In: BMJ Yale. 2020.

[5] Haarala, A. et al.: Heart rate variability is independently associated with C-reactive protein but not with serum amyloid A. The Cardiovascular Risk in Young Finns Study. In: Eur J Clin Invest, 2011 Sept:41(9): 951-7.

[6] Williams DP. et al.: Heart rate variability and inflammation: A meta-analysis of human studies. In: Brain Behav Immun. 2019.

[7] Graeme C. Clark et al.: Targeting the „cytokine storm” for therapeutic benefit. In: Clin Vaccine Immunol. 2013:20(3):319-327-

[8] Fábio M, de Castilho: Heart rate variability as predictor of mortality in sepsis: A prospective cohort study. In: PLoS One. 2017: 12(6). e0180060.

[9] Kohoutova, M. et al.:Vagus nerve stimulation attenuates multiple organ dysfunction in resuscitated porcine progressive sepsis. In: Critical Care Medicine. 2019:47,6:e461-469.

[10] Ruan, Q. et al.:  Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. In:Intensive Care Medicine 2020.

[11] Zheng, YY. et al.: COVID-19 and the cardiovascular system. In: Nature Reviews Cardiology: 2020.

[12] Ling, N. et al.: Heart rate variability in children with myocarditis presenting with ventricular arrhythmias. In: European Review for Medical and Pharmacological Sciences, 2018: 22: 1102-1105

[13] Wu, H. et al.: Vagus Nerve through 7 nAChR Modulates Lung Infection and Inflammation: Models, Cells, and Signals. In: BioMed Research International Volume 2014, Article ID 283525, 20 pages.

[14] Dos Santos, C. et al: Stimulation of the Efferent Vagus Nerve Mitigates Acute Lung Injury and Ventilator Induced Lung Injury. In: FASEB Journal, 2010: 24(1)Supplement

[15] Johansson BL: C-peptide improves autonomic nerve function in IDDM patients. In: Diabetologia. 1996 Jun;39(6):687-95.

[16] Kimura, K. et al: Proinsulin C-peptide activates vagus efferent output in rats. In: Peptides. 2005:26(12):2547-53.