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Immunol."],"abstract":"<jats:p>The outbreak of coronavirus disease 2019 (COVID-19) underlined the urgent need for alleviating cytokine storm. We propose here that activating the cholinergic anti-inflammatory pathway (CAP) is a potential therapeutic strategy. However, there is currently no approved drugs targeting the regulatory pathway. It is evident that nicotine, anisodamine and some herb medicine, activate the CAP and exert anti-inflammation action <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. As the vagus nerve affects both inflammation and specific immune response, we propose that vagus nerve stimulation by invasive or non-invasive devices and acupuncture at ST36, PC6, or GV20, are also feasible approaches to activate the CAP and control COVID-19. It is worth to investigate the efficacy and safety of the strategy in patients with COVID-19.<\/jats:p>","DOI":"10.3389\/fimmu.2020.595342","type":"journal-article","created":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T23:16:20Z","timestamp":1612826180000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":34,"title":["Activation of the Cholinergic Anti-Inflammatory Pathway as a Novel Therapeutic Strategy for COVID-19"],"prefix":"10.3389","volume":"11","author":[{"given":"Zhen","family":"Qin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kefa","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding-Feng","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(20)30251-8","article-title":"Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding","volume":"395","author":"Lu","year":"2020","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30920-X","article-title":"SARS-CoV-2 and viral sepsis: observations and hypotheses","volume":"395","author":"Li","year":"2020","journal-title":"Lancet"},{"key":"B3","unstructured":""},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.3377","article-title":"Obesity and diabetes as high-risk factors for severe coronavirus disease 2019 (Covid-19)","author":"Zhou","year":"2020","journal-title":"Diabetes Metab Res Rev"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcha.2020.100557","article-title":"Coronavirus disease 2019 and cardiovascular system: A narrative review","volume":"29","author":"Kwenandar","year":"2020","journal-title":"Int J Cardiol Heart Vasc"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30211-7","article-title":"Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study","volume":"395","author":"Chen","year":"2020","journal-title":"Lancet"},{"key":"B7","unstructured":""},{"key":"B8","unstructured":""},{"key":"B9","unstructured":""},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb8925","article-title":"Cytokine release syndrome in severe COVID-19","volume":"368","author":"Moore","year":"2020","journal-title":"Science"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00127-20","article-title":"Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus","volume":"94","author":"Wan","year":"2020","journal-title":"J Virol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/s10753-020-01337-3","article-title":"Inflammation Triggered by SARS-CoV-2 and ACE2 Augment Drives Multiple Organ Failure of Severe COVID-19: Molecular Mechanisms and Implications","volume":"44","author":"Iwasaki","year":"2021","journal-title":"Inflammation"},{"key":"B13","doi-asserted-by":"publisher","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":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.6776","article-title":"Cytokine storm in COVID-19 and parthenolide: Preclinical evidence","volume":"34","author":"Bahrami","year":"2020","journal-title":"Phytother Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30317-2","article-title":"Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury","volume":"395","author":"Russell","year":"2020","journal-title":"Lancet"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.08.039","article-title":"Anthracyclines induce DNA damage response-mediated protection against severe sepsis","volume":"39","author":"Figueiredo","year":"2013","journal-title":"Immunity"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.3332\/ecancer.2020.1023","article-title":"COVID-19 and treatment with NSAIDs and corticosteroids: should we be limiting their use in the clinical setting","volume":"14","author":"Russell","year":"2020","journal-title":"Ecancermedicalscience"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.104849","article-title":"Italian Society of P. 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