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

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.

Psychological and Cognitive Effects of Long COVID: A Narrative Review Focusing on the Assessment and Rehabilitative Approach

“…Other technologies are available and approved for clinical use but have not been extensively studied in the treatment of the cytokine storm in COVID-19 patients [ 124 ]. Indeed, brain and immune response are bidirectionally correlated, acting throughout the body as potential targets for noninvasive neuromodulatory approaches [ 125 ].…”

Understanding the Pivotal Role of the Vagus Nerve in Health from Pandemics

“…For instance, in addition to the impact of smoking status in humans, CHRFAM7A is a unique human gene (expressed neither in primates nor rodents) that encodes a dominant negative inhibitor of the α7 nicotinic acetylcholine receptor, making it difficult to infer results in humans from animal models’ data [ 84 ]. The International Consortium on Neuromodulation for COVID-19 (ICNC, , accessed on 15 May 2020) was created during spring 2020 in order to support the rapid deployment and clinical validation of neuromodulation technologies—especially VNS devices—through multiple modalities, including electricity (transcutaneous cervical or auricular stimulation), ultrasound (percutaneous needle electrode close to the cervical vagus nerve), and focused ultrasound (spleen, liver) (see [ 85 ] for a review). Because of their absence of side effects, non-invasive solutions such as monitoring and restoring the vagal tone should also be systematically assessed in clinical trials during epidemics—for instance, in the recent acute and severe hepatitis of unknown etiology in children, probably involving an adenovirus [ 86 ], or in case of a monkeypox epidemic [ 87 ].…”

Vagus Nerve Stimulation for the Treatment of Post–COVID-19 Condition

“…The authors of the review, however, did report that several studies are ongoing to assess neurostimulation devices for conditions unrelated to COVID-19, but which may have similar mechanisms of action. 25…”