Implications for Neuromodulation Therapy to Control Inflammation and Related Organ Dysfunction in COVID-19

Marat Fudim, Yawar J Qadri, Kamrouz Ghadimi, David B MacLeod, Jeroen Molinger, Jonathan P Piccini, John Whittle, Paul E Wischmeyer, Manesh R Patel, Luis Ulloa, Marat Fudim, Yawar J Qadri, Kamrouz Ghadimi, David B MacLeod, Jeroen Molinger, Jonathan P Piccini, John Whittle, Paul E Wischmeyer, Manesh R Patel, Luis Ulloa

Abstract

COVID-19 is a syndrome that includes more than just isolated respiratory disease, as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) also interacts with the cardiovascular, nervous, renal, and immune system at multiple levels, increasing morbidity in patients with underlying cardiometabolic conditions and inducing myocardial injury or dysfunction. Emerging evidence suggests that patients with the highest rate of morbidity and mortality following SARS-CoV2 infection have also developed a hyperinflammatory syndrome (also termed cytokine release syndrome). We lay out the potential contribution of a dysfunction in autonomic tone to the cytokine release syndrome and related multiorgan damage in COVID-19. We hypothesize that a cholinergic anti-inflammatory pathway could be targeted as a therapeutic avenue. Graphical Abstract .

Keywords: ACE2; COVID-19; SARS-CoV2; Vagus; Vagus nerve stimulation.

Conflict of interest statement

Marat Fudim consults for AxonTherapies, Daxor, Edwards, and Galvani, and received non-monetary support from Parasym. Kamrouz Ghadimi consults for Uptodate® for coagulation and blood management; receives grant support from NIH T32GM008600 and Duke Health; has previous support from Octapharma. Jonathan Piccini receives grants for clinical research from Abbott, American Heart Association, Association for the Advancement of Medical Instrumentation, Bayer, Boston Scientific, NHLBI, and Philips, and serves as a consultant to Abbott, Allergan, ARCA Biopharma, Biotronik, Boston Scientific, LivaNova, Medtronic, Milestone, Myokardia, Sanofi, Philips, and Up-to-Date. Manesh Patel receives grant support from Medtronic, Bayer, Janssen, and Heartflow, and consults for Bayer, Janssen, and Heartflow. All other authors report no relevant conflicts of interest.

Figures

Graphical Abstract
Graphical Abstract
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Figure 1
Figure 1
Connection between the vagus nerve and immune system. ACh, acetylcholine; nAChR, nicotinic acetylcholine receptor; RAAS, renin angiotensin aldosterone system; ACE2, angiotensin-converting enzyme 2; SARS-CoV2, severe acute respiratory syndrome–coronavirus

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