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Review
. 2022 Jul 14:13:897124.
doi: 10.3389/fneur.2022.897124. eCollection 2022.

Neuromodulation Strategies to Reduce Inflammation and Improve Lung Complications in COVID-19 Patients

Christopher J Czura  1 , Marom Bikson  2 , Leigh Charvet  3 , Jiande D Z Chen  4 , Manfred Franke  5 , Marat Fudim  6 , Eric Grigsby  7 , Sam Hamner  8 , Jared M Huston  9 , Navid Khodaparast  10 , Elliot Krames  11 , Bruce J Simon  12 , Peter Staats  13 , Kristl Vonck  14
Affiliations
Review

Neuromodulation Strategies to Reduce Inflammation and Improve Lung Complications in COVID-19 Patients

Christopher J Czura et al. Front Neurol. .

Abstract

Since the outbreak of the COVID-19 pandemic, races across academia and industry have been initiated to identify and develop disease modifying or preventative therapeutic strategies has been initiated. The primary focus has been on pharmacological treatment of the immune and respiratory system and the development of a vaccine. The hyperinflammatory state ("cytokine storm") observed in many cases of COVID-19 indicates a prognostically negative disease progression that may lead to respiratory distress, multiple organ failure, shock, and death. Many critically ill patients continue to be at risk for significant, long-lasting morbidity or mortality. The human immune and respiratory systems are heavily regulated by the central nervous system, and intervention in the signaling of these neural pathways may permit targeted therapeutic control of excessive inflammation and pulmonary bronchoconstriction. Several technologies, both invasive and non-invasive, are available and approved for clinical use, but have not been extensively studied in treatment of the cytokine storm in COVID-19 patients. This manuscript provides an overview of the role of the nervous system in inflammation and respiration, the current understanding of neuromodulatory techniques from preclinical and clinical studies and provides a rationale for testing non-invasive neuromodulation to modulate acute systemic inflammation and respiratory dysfunction caused by SARS-CoV-2 and potentially other pathogens. The authors of this manuscript have co-founded the International Consortium on Neuromodulation for COVID-19 to advocate for and support studies of these technologies in the current coronavirus pandemic.

Keywords: COVID-19; acute respiratory distress (ARDS); cranial nerve stimulation; cytokine storm; non-invasive; sacral nerve electrical stimulation; vagus nerve (VN) stimulation.

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Conflict of interest statement

CC is an equity holder of Convergent Medical Technologies, Inc., reports personal fees from electroCore Inc., and Spark Biomedical, and has issued and pending patents related to vagus nerve stimulation to control bleeding and inflammation. MB reports personal fees from Soterix Medical, grants from Google X, personal fees from Halo Neuroscience, outside the submitted work; in addition, he has a patent Brain Stimulation issued. MFr reports pending patent applications describing injectable electrode structures for Neuronoff, Inc., and is an employee and equity holder of Neuronoff, Inc. He further reports issued patents for selective Vagus nerve stimulation and selective electrical vagal block for regulation of autonomic functions such as heart rate and blood pressure for Boston Scientific. MFu reports personal fees from Axon Therapies, CVRx, Daxor, Edwards Life Sciences, Galvani, and Respicardia, outside the submitted work. SH is an employee and equity holder of Cala Health. NK reports a patent devices and methods for reducing inflammation using electrical stimulation pending. BS reports personal fees from electroCore, and reports patents issued and pending related to transcutaneous cervical vagus nerve stimulation. PS is an employee and equity holder of electroCore, and reports patents issued and pending related to transcutaneous cervical vagus nerve stimulation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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