Non-invasive Vagus Nerve Stimulation for COVID-19: Results From a Randomized Controlled Trial (SAVIOR I)
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- Evaluated articles (Rapid Reviews Infectious Diseases)
Abstract
Severe coronavirus disease 2019 (COVID-19) is characterized, in part, by an excessive inflammatory response. Evidence from animal and human studies suggests that vagus nerve stimulation can lead to reduced levels of various biomarkers of inflammation. We conducted a prospective randomized controlled study (SAVIOR-I) to assess the feasibility, efficacy, and safety of non-invasive vagus nerve stimulation (nVNS) for the treatment of respiratory symptoms and inflammatory markers among patients who were hospitalized for COVID-19 ( ClinicalTrials.gov identifier: NCT04368156).
Methods
Participants were randomly assigned in a 1:1 allocation to receive either the standard of care (SoC) alone or nVNS therapy plus the SoC. The nVNS group received 2 consecutive 2-min doses of nVNS 3 times daily as prophylaxis. Efficacy and safety were evaluated via the incidence of specific clinical events, inflammatory biomarker levels, and the occurrence of adverse events.
Results
Of the 110 participants who were enrolled and randomly assigned, 97 (nVNS, n = 47; SoC, n = 50) had sufficient available data and comprised the evaluable population. C-reactive protein (CRP) levels decreased from baseline to a significantly greater degree in the nVNS group than in the SoC group at day 5 and overall (i.e., all postbaseline data points collected through day 5, combined). Procalcitonin level also showed significantly greater decreases from baseline to day 5 in the nVNS group than in the SoC group. D-dimer levels were decreased from baseline for the nVNS group and increased from baseline for the SoC group at day 5 and overall, although the difference between the treatment groups did not reach statistical significance. No significant treatment differences were seen for clinical respiratory outcomes or any of the other biochemical markers evaluated. No serious nVNS-related adverse events occurred during the study.
Conclusions
nVNS therapy led to significant reductions in levels of inflammatory markers, specifically CRP and procalcitonin. Because nVNS has multiple mechanisms of action that may be relevant to COVID-19, additional research into its potential use earlier in the course of COVID-19 and its potential to mitigate some of the symptoms associated with post-acute sequelae of COVID-19 is warranted.
Article activity feed
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Claire Marie-Rangon
Review 2: "Non-invasive Vagus Nerve Stimulation for Respiratory Symptoms of COVID-19: Results From a Randomized Controlled Trial (SAVIOR I)"
This preprint claims that nVNS therapy has the potential to reduce pro-inflammatory cytokines in patients with COVID-19. Both reviewers agree on the importance of the issues it raised. They suggested the inclusion of cost-effectiveness analysis in the ongoing SAVIOR II trial.
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Abrahão Fontes Baptista
Review 1: "Non-invasive Vagus Nerve Stimulation for Respiratory Symptoms of COVID-19: Results From a Randomized Controlled Trial (SAVIOR I)"
This preprint claims that nVNS therapy has the potential to reduce pro-inflammatory cytokines in patients with COVID-19. Both reviewers agree on the importance of the issues it raised. They suggested the inclusion of cost-effectiveness analysis in the ongoing SAVIOR II trial.
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Strength of evidence
Reviewers: Abrahão Fontes Baptista (Federal University of ABC) | 📒📒📒◻️◻️
Claire-Marie Rangon (Hospital Foundation Adolphe De Rothschild) | 📗📗📗📗◻️ -
SciScore for 10.1101/2021.09.24.21264045: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The clinical research plan was reviewed and approved by an institutional review board and an ethics committee before patient enrollment.
Consent: All patients provided written informed consent before participation.Sex as a biological variable not detected. Randomization Participants: This prospective randomized controlled study was conducted at Hospital Clínico Universitario de Valencia (Valencia, Spain). Blinding not detected. Power Analysis Statistical Analyses: As this was the first study of nVNS for the treatment of patients hospitalized with COVID-19, there are no previously published data on the anticipated effect size in humans, and a formal power analysis could not be performed. Table …
SciScore for 10.1101/2021.09.24.21264045: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The clinical research plan was reviewed and approved by an institutional review board and an ethics committee before patient enrollment.
Consent: All patients provided written informed consent before participation.Sex as a biological variable not detected. Randomization Participants: This prospective randomized controlled study was conducted at Hospital Clínico Universitario de Valencia (Valencia, Spain). Blinding not detected. Power Analysis Statistical Analyses: As this was the first study of nVNS for the treatment of patients hospitalized with COVID-19, there are no previously published data on the anticipated effect size in humans, and a formal power analysis could not be performed. Table 2: Resources
Antibodies Sentences Resources As the pandemic progressed, treatment protocols evolved to incorporate glucocorticoids, antivirals, monoclonal antibodies, and prone mechanical ventilation. antivirals,suggested: NoneSoftware and Algorithms Sentences Resources Statistical analyses were performed with SAS 9.4 (SAS Institute Inc.). SAS Institutesuggested: (Statistical Analysis System, RRID:SCR_008567)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04368156 Active, not recruiting Study Assessing Vagus Nerve Stimulation in CoViD-19 Respirat… NCT04382391 Active, not recruiting Study Assessing Vagus Nerve Stimulation in CoViD-19 Respirat… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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