Percutaneous Auricular Vagus Nerve Stimulation Reduces Inflammation in Critical Covid-19 Patients

Tamara Seitz; József Constantin Szeles; Reinhard Kitzberger; Johannes Holbik; Alexander Grieb; Hermann Wolf; Hüseyin Akyaman; Felix Lucny; Alexander Tychera; Stephanie Neuhold; Alexander Zoufaly; Christoph Wenisch; Eugenijus Kaniusas

doi:10.3389/fphys.2022.897257

Percutaneous Auricular Vagus Nerve Stimulation Reduces Inflammation in Critical Covid-19 Patients

Front Physiol. 2022 Jul 4:13:897257. doi: 10.3389/fphys.2022.897257. eCollection 2022.

Authors

Affiliations

¹ Department of Infectious Diseases and Tropical Medicine, Klinik Favoriten, Vienna, Austria.
² Department of General Surgery, Division of Vascular Surgery, Medical University of Vienna Center for Wound Surgery, Health Service Center of Vienna Privat Clinics, Vienna, Austria.
³ Immunology Outpatient Clinic, Vienna, Austria.
⁴ Medical School, Sigmund Freud Private University, Vienna, Austria.
⁵ Faculty of Electrical Engineering and Information Technology, Institute of Biomedical Electronics, Vienna University of Technology (TU Wien), Vienna, Austria.

Abstract

Covid-19 is an infectious disease associated with cytokine storms and derailed sympatho-vagal balance leading to respiratory distress, hypoxemia and cardiovascular damage. We applied the auricular vagus nerve stimulation to modulate the parasympathetic nervous system, activate the associated anti-inflammatory pathways, and reestablish the abnormal sympatho-vagal balance. aVNS is performed percutaneously using miniature needle electrodes in ear regions innervated by the auricular vagus nerve. In terms of a randomized prospective study, chronic aVNS is started in critical, but not yet ventilated Covid-19 patients during their stay at the intensive care unit. The results show decreased pro-inflammatory parameters, e.g. a reduction of CRP levels by 32% after 1 day of aVNS and 80% over 7 days (from the mean 151.9 mg/dl to 31.5 mg/dl) or similarly a reduction of TNFalpha levels by 58.1% over 7 days (from a mean 19.3 pg/ml to 8.1 pg/ml) and coagulation parameters, e.g. reduction of DDIMER levels by 66% over 7 days (from a mean 4.5 μg/ml to 1.5 μg/ml) and increased anti-inflammatory parameters, e.g. an increase of IL-10 levels by 66% over 7 days (from the mean 2.7 pg/ml to 7 pg/ml) over the aVNS duration without collateral effects. aVNS proved to be a safe clinical procedure and could effectively supplement treatment of critical Covid-19 patients while preventing devastating over-inflammation.

Keywords: COVID-19; SARS-CoV-2; aVNS; cytokine storm; hyperinflammation; nervus vagus stimulation.