{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T22:17:11Z","timestamp":1781043431774,"version":"3.54.1"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T00:00:00Z","timestamp":1620345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) through excessive end organ inflammation. Despite improved understanding of the pathophysiology, management, and the great efforts worldwide to produce effective drugs, death rates of COVID-19 patients remain unacceptably high, and effective treatment is unfortunately lacking. Pharmacological strategies aimed at modulating inflammation in COVID-19 are being evaluated worldwide. Several drug therapies targeting this excessive inflammation, such as tocilizumab, an interleukin (IL)-6 inhibitor, corticosteroids, programmed cell death protein (PD)-1\/PD-L1 checkpoint inhibition, cytokine-adsorption devices, and intravenous immunoglobulin have been identified as potentially useful and reliable approaches to counteract the cytokine storm. However, little attention is currently paid for non-drug therapeutic strategies targeting inflammatory and immunological processes that may be useful for reducing COVID-19-induced complications and improving patient outcome. Vagus nerve stimulation attenuates inflammation both in experimental models and preliminary data in human. Modulating the activity of cholinergic anti-inflammatory pathways (CAPs) described by the group of KJ Tracey has indeed become an important target of therapeutic research strategies for inflammatory diseases and sepsis. Non-invasive transcutaneous vagal nerve stimulation (t-VNS), as a non-pharmacological adjuvant, may help reduce the burden of COVID-19 and deserve to be investigated. VNS as an adjunct therapy in COVID-19 patients should be investigated in clinical trials. Two clinical trials on this topic are currently underway (NCT04382391 and NCT04368156). The results of these trials will be informative, but additional larger studies are needed.<\/jats:p>","DOI":"10.3389\/fmed.2021.625836","type":"journal-article","created":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T05:14:18Z","timestamp":1620364458000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":37,"title":["Vagus Nerve Stimulation: A Potential Adjunct Therapy for COVID-19"],"prefix":"10.3389","volume":"8","author":[{"given":"Eric","family":"Azabou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rania","family":"Bounab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Heming","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djillali","family":"Annane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2085","DOI":"10.1007\/s10067-020-05190-5","article-title":"Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment","volume":"39","author":"Soy","year":"2020","journal-title":"Clin Rheumatol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1080\/15368378.2020.1830290","article-title":"Infusion of HLA-matched and static magnetic field-exposed allogenic lymphocytes treating lymphocytopenia and cytokine storm syndrome: a treatment proposal for COVID-19 patients","volume":"40","author":"Vergallo","year":"2020","journal-title":"Electromagn Biol Med"},{"key":"B3","first-page":"695","article-title":"Role of cytokines and pathogen associated molecular pattern receptors in sepsis","volume":"59","author":"Klucinski","year":"2005","journal-title":"Przegl Epidemiol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2063","DOI":"10.1056\/NEJMc1312359","article-title":"Severe sepsis and septic shock","volume":"369","author":"Angus","year":"2013","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"70","DOI":"10.3389\/fendo.2016.00070","article-title":"The role of ACTH and corticosteroids for sepsis and septic shock: an update","volume":"7","author":"Annane","year":"2016","journal-title":"Front Endocrinol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"5526","DOI":"10.1007\/s12035-016-0094-x","article-title":"Vasopressin impairment during sepsis is associated with hypothalamic intrinsic apoptotic pathway and microglial activation","volume":"54","author":"da Costa","year":"2016","journal-title":"Mol Neurobiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1097\/CCM.0b013e31816f48f2","article-title":"Hydrocortisone effects on cardiovascular variability in septic shock: a spectral analysis approach","volume":"36","author":"Aboab","year":"2008","journal-title":"Crit Care Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1164\/ajrccm.160.2.9810073","article-title":"Inappropriate sympathetic activation at onset of septic shock: a spectral analysis approach","volume":"160","author":"Annane","year":"1999","journal-title":"Am J Respir Crit Care Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.lpm.2016.03.004","article-title":"Adjunctive treatment in septic shock: what's next?","volume":"45","author":"Annane","year":"2016","journal-title":"Presse Med"},{"key":"B10","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s13613-016-0165-1","article-title":"Design and conduct of the activated protein C and corticosteroids for human septic shock (APROCCHSS) trial","volume":"6","author":"Annane","year":"2016","journal-title":"Ann Intensive Care"},{"key":"B11","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1007\/s13365-020-00908-2","article-title":"Autonomic dysfunction heralding acute motor axonal neuropathy in COVID-19","volume":"26","author":"Ghosh","year":"2020","journal-title":"J Neurovirol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1007\/s10286-020-00714-0","article-title":"The extended autonomic system, dyshomeostasis, and COVID-19","volume":"30","author":"Goldstein","year":"2020","journal-title":"Clin Auton Res"},{"key":"B13","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1007\/s10286-020-00715-z","article-title":"Is 'happy hypoxia' in COVID-19 a disorder of autonomic interoception? 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