Transcutaneous Vagus Nerve Stimulation is Associated with Lower Mechanical Ventilation and Mortality in COVID-19 Patients: An interim Safety Analysis

Objective: To evaluate the safety and efficacy of transcutaneous vagus nerve stimulation in preventing respiratory failure and improving survival in hospitalized COVID-19 patients. Design, Setting, and Participants: Interim analysis of an ongoing single-arm, uncontrolled open-label, observational trial to assess the transcutaneous vagus nerve stimulation (tVNS) in hospitalized SARS-CoV-2 infected subjects. Eligible subjects are 18 years old or older requiring hospitalization for COVID-19pneumonia. Results: The 25 subjects enrolled with a mean age of 52.2 (22-80). Mechanical ventilation was required in only 2 (8%) cases. One survived and 1 one died. Although 4 (16%) of the 25 hospitalized subjects died, only 1 (4%) was attributed to respiratory failure. Relative to other reported COVID-19 hospitalization outcomes data, our mortality rate of 16% (4 of 25) is lower than many other reported cohorts 10.2% – 50%. Only 8% (2 of 25) of subjects required mechanical ventilation comparing favorably to 7.4%-79% of subjects requiring mechanical ventilation in other cohorts. Adverse events associated with tVNS occurred in only 2 subjects (8%) and consisted of reversible oral paresthesia and orthostatic hypotension. Conclusion and Relevance: In this interim report of tVNS in COVID-19 pneumonia, patients had a low rate of adverse events, infrequent use of mechanical ventilation, and a high rate of survival. Several other studies have shown a wide range of in hospital mortality (14-50%) and the requirement of mechanical ventilation (7-79%). The interim analysis found the mortality rate and the frequency of mechanical ventilation to be less than almost all other large COVID-19 cohorts. Only mild and self-limiting adverse events tVNS occurred in 2 subjects highlighting the safety of vagus stimulation. The study is slated to enroll a minimum of 50 subjects. Trial Registration: ClinicalTrials.gov Identifier: NTC04379037.