Use of Vagus Nerve Stimulation and Vagal Maneuvers as Adjuvant Therapy for COVID-19 Patients
Abstract
At present there is no effective specific antiviral drug to treat the ongoing COVID-19 pandemic that has already infected millions of individual and caused hundreds of thousand deaths worldwide. There is strong indication that a cytokine storm is responsible for the severity of COVID-19 patients. Pilot studies using IL-6 receptor inhibitors such as Tolicizumab have shown promising results. However, since the cytokine storm is a complex systemic inflammatory response involving multiple cytokines it can be hypothesized that a “paninhibition†of cytokines and/or cytokine receptors will be more effective. However, at the same time this strategy may cause more adverse effects. In this article, we propose the application of Vagus Nerve Stimulation (NVS) and/or some forms of vagal maneuvers as adjuvant therapies to prevent and/or mitigate the cytokine response in COVID-19 patients. This proposal is based on the ability of NVS and to decrease the production of IL-6 and other cytokines. The potential application of the diving response (one form of vagal maneuver), that has been shown to confer intrinsic resistance to inflammation in the blood of diving mammals, is also discussed as adjuvant therapy for COVID-19 patients.
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Doi: 10.28991/SciMedJ-2021-03-SI-2
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Tanne, J. H. (2020) Covid-19: Pfizer-BioNTech vaccine is rolled out in US. Bmj, 371 m4836. doi:10.1136/bmj.m4836.
Cabanillas, B., Akdis, C. and Novak, N. (2020) Allergic reactions to the first COVID-19 vaccine: a potential role of Polyethylene glycol? Allergy. doi:10.1111/all.14711.
Soiza, R. L., Scicluna, C. and Thomson, E. C. (2020) Efficacy and safety of COVID-19 vaccines in older people. Age Ageing. doi:10.1093/ageing/afaa274.
Mills, M. C. and Salisbury, D. (2020) The challenges of distributing COVID-19 vaccinations. EClinicalMedicine 100674. doi:10.1016/j.eclinm.2020.100674.
Zhang, J., Xie, B. and Hashimoto, K. (2020) Current status of potential therapeutic candidates for the COVID-19 crisis. Brain Behav Immun. doi:10.1016/j.bbi.2020.04.046.
Guerin, C., Reignier, J., Richard, J. C., Beuret, P., Gacouin, A., Boulain, T., Mercier, E., Badet, M., Mercat, A., Baudin, O., Clavel, M., Chatellier, D., Jaber, S., Rosselli, S., Mancebo, J., Sirodot, M., Hilbert, G., Bengler, C., Richecoeur, J., Gainnier, M., Bayle, F., Bourdin, G., Leray, V., Girard, R., Baboi, L. and Ayzac, L. (2013) Prone positioning in severe acute respiratory distress syndrome. N Engl J Med, 368(23), 2159-2168. doi:10.1056/NEJMoa1214103.
Meng, L., Qiu, H., Wan, L., Ai, Y., Xue, Z., Guo, Q., Deshpande, R., Zhang, L., Meng, J., Tong, C., Liu, H. and Xiong, L. (2020) Intubation and Ventilation amid the COVID-19 Outbreak: Wuhan's Experience. Anesthesiology. doi:10.1097/aln.0000000000003296.
Barrasa, H., Rello, J., Tejada, S., Martin, A., Balziskueta, G., Vinuesa, C., Fernandez-Miret, B., Villagra, A., Vallejo, A., Sebastian, A. S., Cabanes, S., Iribarren, S., Fonseca, F. and Maynar, J. (2020) SARS-Cov-2 in Spanish Intensive Care: Early Experience with 15-day Survival In Vitoria. Anaesth Crit Care Pain Med. doi:10.1016/j.accpm.2020.04.001.
Chen, N., Zhou, M., Dong, X., Qu, J., Gong, F., Han, Y., Qiu, Y., Wang, J., Liu, Y., Wei, Y., Xia, J., Yu, T., Zhang, X. and Zhang, L. (2020) Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet, 395(10223), 507-513. doi:10.1016/s0140-6736(20)30211-7.
Zhang, R., Wang, X., Ni, L., Di, X., Ma, B., Niu, S., Liu, C. and Reiter, R. J. (2020) COVID-19: Melatonin as a potential adjuvant treatment. Life Sci, 250 117583. doi:10.1016/j.lfs.2020.117583.
Chigr, F., Merzouki, M. and Najimi, M. (2020) Autonomic Brain Centers and Pathophysiology of COVID-19. ACS Chem Neurosci, 11(11), 1520-1522. doi:10.1021/acschemneuro.0c00265.
Dey, J., Alam, M. T., Chandra, S., Gupta, J., Ray, U., Srivastava, A. K. and Tripathi, P. P. (2020) Neuroinvasion of SARS-CoV-2 may play a role in the breakdown of respiratory center of the brain. J Med Virol. doi: 10.1002/jmv.26521.
Jakhmola, S., Indari, O., Chatterjee, S. and Jha, H. C. (2020) SARS-CoV-2, an Underestimated Pathogen of the Nervous System. SN Compr Clin Med 1-10. doi:10.1007/s42399-020-00522-7.
Maurier, F., Godbert, B. and Perrin, J. (2020) Respiratory Distress in SARS-CoV-2 without Lung Damage: Phrenic Paralysis Should Be Considered in COVID-19 Infection. Eur J Case Rep Intern Med, 7(6), 001728. doi:10.12890/2020_001728.
Pavlov, V. A. (2020) The evolving obesity challenge: Targeting the vagus nerve and the inflammatory reflex in the response. Pharmacol Ther 107794. doi:10.1016/j.pharmthera.2020.107794.
Ahmad, F. (2020) COVID-19 induced ARDS, and the use of galantamine to activate the cholinergic anti-inflammatory pathway. Med Hypotheses, 145 110331. doi:10.1016/j.mehy.2020.110331.
Andersson, U. (2020) The cholinergic anti-inflammatory pathway alleviates acute lung injury. Mol Med, 26(1), 64. doi:10.1186/s10020-020-00184-0.
Bonaz, B., Sinniger, V. and Pellissier, S. (2020) Targeting the cholinergic anti-inflammatory pathway with vagus nerve stimulation in patients with Covid-19? Bioelectron Med, 6 15. doi:10.1186/s42234-020-00051-7.
Ten Hove, A. S., Brinkman, D. J., Li Yim, A. Y. F., Verseijden, C., Hakvoort, T. B. M., Admiraal, I., Welting, O., van Hamersveld, P. H. P., Sinniger, V., Bonaz, B., Luyer, M. D. and de Jonge, W. J. (2020) The role of nicotinic receptors in SARS-CoV-2 receptor ACE2 expression in intestinal epithelia. Bioelectron Med, 6(1), 20. doi:10.1186/s42234-020-00057-1.
Ye, Q., Wang, B. and Mao, J. (2020) The pathogenesis and treatment of the `Cytokine Storm' in COVID-19. J Infect. doi:10.1016/j.jinf.2020.03.037.
Luo, P., Liu, Y., Qiu, L., Liu, X., Liu, D. and Li, J. (2020) Tocilizumab treatment in COVID-19: A single center experience. J Med Virol. doi:10.1002/jmv.25801.
Cellina, M., Orsi, M., Bombaci, F., Sala, M., Marino, P. and Oliva, G. (2020) Favorable changes of CT findings in a patient with COVID-19 pneumonia after treatment with tocilizumab. Diagn Interv Imaging. doi:10.1016/j.diii.2020.03.010.
De Luna, G., Habibi, A., Deux, J. F., Colard, M., d'Alexandry d'Orengiani, A., Schlemmer, F., Joher, N., Kassasseya, C., Pawlotsky, J. M., Ourghanlian, C., Michel, M., Mekontso-Dessap, A. and Bartolucci, P. (2020) Rapid and Severe Covid-19 Pneumonia with Severe Acute Chest Syndrome in a Sickle Cell Patient Successfully Treated with Tocilizumab. Am J Hematol. doi:10.1002/ajh.25833.
Fontana, F., Alfano, G., Mori, G., Amurri, A., Lorenzo, T., Ballestri, M., Leonelli, M., Facchini, F., Damiano, F., Magistroni, R. and Cappelli, G. (2020) Covid-19 pneumonia in a kidney transplant recipient successfully treated with Tocilizumab and Hydroxychloroquine. Am J Transplant. doi:10.1111/ajt.15935.
Michot, J. M., Albiges, L., Chaput, N., Saada, V., Pommeret, F., Griscelli, F., Balleyguier, C., Besse, B., Marabelle, A., Netzer, F., Merad, M., Robert, C., Barlesi, F., Gachot, B. and Stoclin, A. (2020) Tocilizumab, an anti-IL6 receptor antibody, to treat Covid-19-related respiratory failure: a case report. Ann Oncol. doi: 10.1016/j.annonc.2020.03.300.
Mihai, C., Dobrota, R., Schroder, M., Garaiman, A., Jordan, S., Becker, M. O., Maurer, B. and Distler, O. (2020) COVID-19 in a patient with systemic sclerosis treated with tocilizumab for SSc-ILD. Ann Rheum Dis, 79(5), 668-669. doi:10.1136/annrheumdis-2020-217442.
Zhang, X., Song, K., Tong, F., Fei, M., Guo, H., Lu, Z., Wang, J. and Zheng, C. (2020) First case of COVID-19 in a patient with multiple myeloma successfully treated with tocilizumab. Blood Adv, 4(7), 1307-1310. doi:10.1182/bloodadvances.2020001907.
Jacobs, J. P., Stammers, A. H., St Louis, J., Hayanga, J. W. A., Firstenberg, M. S., Mongero, L. B., Tesdahl, E. A., Rajagopal, K., Cheema, F. H., Coley, T., Badhwar, V., Sestokas, A. K. and Slepian, M. J. (2020) Extracorporeal Membrane Oxygenation in the Treatment of Severe Pulmonary and Cardiac Compromise in COVID-19: Experience with 32 patients. Asaio j. doi:10.1097/mat.0000000000001185.
Behrens, E. M. and Koretzky, G. A. (2017) Review: Cytokine Storm Syndrome: Looking Toward the Precision Medicine Era. Arthritis Rheumatol, 69(6), 1135-1143. doi:10.1002/art.40071.
Morrison, A. R., Johnson, J. M., Ramesh, M., Bradley, P., Jennings, J. and Smith, Z. R. (2020) Letter to the Editor: Acute hypertriglyceridemia in patients with COVID-19 receiving tocilizumab. J Med Virol. doi:10.1002/jmv.25907.
Koopman, F. A., Chavan, S. S., Miljko, S., Grazio, S., Sokolovic, S., Schuurman, P. R., Mehta, A. D., Levine, Y. A., Faltys, M., Zitnik, R., Tracey, K. J. and Tak, P. P. (2016) Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. Proc Natl Acad Sci U S A, 113(29), 8284-8289. doi:10.1073/pnas.1605635113.
Nie, Z., Scott, G. D., Weis, P. D., Itakura, A., Fryer, A. D. and Jacoby, D. B. (2011) Role of TNF-alpha in virus-induced airway hyperresponsiveness and neuronal M(2) muscarinic receptor dysfunction. Br J Pharmacol, 164(2b), 444-452. doi:10.1111/j.1476-5381.2011.01393.x.
Flesler, S., Reyes, G., Fortini, S., Ramos, B., Cersósimo, R., Bartuluchi, M., & Caraballo, R. H. (2017). Estimulador del nervio vago: tratamiento en 158 pacientes pediátricos con un largo seguimiento. Revista de NeurologÃa, 64(11), 496. doi:10.33588/rn.6411.2016458.
Revesz, D., Rydenhag, B. and Ben-Menachem, E. (2016) Complications and safety of vagus nerve stimulation: 25 years of experience at a single center. J Neurosurg Pediatr, 18(1), 97-104. doi:10.3171/2016.1.Peds15534.
Bottomley, J. M., LeReun, C., Diamantopoulos, A., Mitchell, S. and Gaynes, B. N. (2019) Vagus nerve stimulation (VNS) therapy in patients with treatment resistant depression: A systematic review and meta-analysis. Compr Psychiatry, 98 152156. doi:10.1016/j.comppsych.2019.152156.
Staats, P., Giannakopoulos, G., Blake, J., Liebler, E. and Levy, R. M. (2020) Use of non-invasive vagus nerve stimulation to treat respiratory symptoms associated with COVID-19: A theoretical hypothesis and early clinical experience. Neuromodulation. doi:10.1111/ner.13172.
Boezaart, A. P. and Botha, D. A. (2020) Treatment of Stage 3 COVID-19 With Transcutaneous Auricular Vagus Nerve Stimulation Drastically Reduces Interleukin-6 Blood Levels: A Report on Two Cases. Neuromodulation. doi:10.1111/ner.13293.
Arnold, R. W. (1999). The human heart rate response profiles to five vagal maneuvers. The Yale journal of biology and medicine, 72(4), 237-244.
Laine Green, A. and Weaver, D. F. (2014) Vagal stimulation by manual carotid sinus massage to acutely suppress seizures. J Clin Neurosci, 21(1), 179-180. doi:10.1016/j.jocn.2013.03.017.
Collins, N. A. and Higgins, G. L., 3rd. (2015) Reconsidering the effectiveness and safety of carotid sinus massage as a therapeutic intervention in patients with supraventricular tachycardia. Am J Emerg Med, 33(6), 807-809. doi:10.1016/j.ajem.2015.02.047.
Lim, H. D., Kim, M. H., Lee, C. Y. and Namgung, U. (2016) Anti-Inflammatory Effects of Acupuncture Stimulation via the Vagus Nerve. PLoS One, 11(3), e0151882. doi:10.1371/journal.pone.0151882.
Niehues, L. J. and Klovenski, V. (2020), StatPearls. StatPearls Publishing, StatPearls Publishing LLC., Treasure Island (FL).
Godek, D. and Freeman, A. M. (2020), StatPearls. StatPearls Publishing. StatPearls Publishing LLC., Treasure Island (FL).
Bagchi, A., Batten, A. J., Levin, M., Allen, K. N., Fitzgerald, M. L., Huckstadt, L. A., Costa, D. P., Buys, E. S. and Hindle, A. G. (2018) Intrinsic anti-inflammatory properties in the serum of two species of deep-diving seal. J Exp Biol, 221(Pt 13). doi:10.1242/jeb.178491.
Alboni, P., Alboni, M. and Gianfranchi, L. (2011) Diving bradycardia: a mechanism of defence against hypoxic damage. J Cardiovasc Med (Hagerstown), 12(6), 422-427. doi:10.2459/JCM.0b013e328344bcdc.
DOI: 10.28991/SciMedJ-2021-03-SI-2
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