Bioelectronic medicine therapies target COVID-19
by James Cavuoto, editor
July 2022 issue, BioElectRx Business Report
Several startup firms and research institutions in the field of bioelectronic medicine have begun to offer therapies for treating COVID-19 and related disorders. In 2020, an influential group of investigators and executives from emerging bioelectronic medicine firms formed a consortium called the International Consortium on Neuromodulation for COVID-19. Earlier this month, 14 members of the consortium published a seminal paper in Frontiers in Neurology on neuromodulation strategies to reduce inflammation and improve lung complications in COVID-19 patients.
The goal of the consortium is to advocate for and support studies of bioelectronic medicine approaches in the current coronavirus pandemic. Commercial firms represented in the group include electroCore Medical Inc., Spark Biomedical, Inc., Cala Health, and NeuronOff Inc. Prominent academic researchers who coauthored the paper include Marom Bikson from CCNY, Leigh Charvet from NYU Grossman School of Medicine, Jiande Chen from the University of Michigan School of Medicine, Marat Fudim from Duke University, Jared Huston from the Zucker School of Medicine, and Kristl Vonck from Ghent University Hospital. Elliot Krames, the founding editor of the journal Neuromodulation: Technology at the Neural Interface and the former president of the International Neuromodulation Society, also contributed to the publication.
In their paper, the authors highlighted the key role that the nervous system plays in regulating the human immune and respiratory systems. “Intervention in the signaling of these neural pathways may permit targeted therapeutic control of excessive inflammation and pulmonary bronchoconstriction,” they wrote. “Several technologies, both invasive and noninvasive, are available and approved for clinical use, but have not been extensively studied in treatment of the cytokine storm in COVID-19 patients.”
The paper discussed strategies involving stimulation of both the vagus nerve and the sacral nerve. The authors pointed out that sacral nerve stimulation has been shown to reduce intestinal inflammation in rodent models of inflammatory bowel diseases, suppress a number of proinflammatory cytokines including TNF, and enhance anti-inflammatory cytokines such as IL-10 in both intestinal tissues and in circulation.
electroCore Inc. was one of the first commercial firms to recognize the potential opportunity represented by COVID-19. In April, the company announced that Frontiers in Neurology published results from an investigator-initiated trial, SAVIOR-1, a prospective, randomized, controlled study evaluating noninvasive VNS using gammaCore Sapphire in patients admitted to the hospital for treatment of COVID-19. The SAVIOR-1 trial was conducted by principal investigator Carlos Tornero, head of the department of anesthesiology, resuscitation and pain therapeutics of the Hospital Clínico Universitario de Valencia, Spain, between April 2020 and February 2021.
The trial targeted patients over 18 years of age and enrolled 110 patients, randomly assigned, with 55 patients in each group. Of the 110 patients, 97 patients (47 in the nVNS treatment group, 50 in the control group) provided baseline demographic and medical history data and were the evaluable population. The study evaluated the safety and feasibility of nVNS when administered in addition to the then-standard of care in patients hospitalized with active SARS-CoV-2 infection compared with the standard of care alone.
The study identified significant treatment differences for certain biomarkers of inflammation. Decreases from baseline in C-reaction protein levels were significantly greater in the nVNS treatment group as compared to the control group throughout the five-day period combined and on day 5 compared to the day 1 baseline period alone. On day 1, CRP levels were highly elevated for 90 percent of all subjects, but by days 3 and 5, the percentage of subjects with normal CRP levels improved markedly in the nVNS group with day 3 CRP levels at 17.9 percent vs. 52 percent in the control. Additionally, the nVNS group had a significantly greater decrease from baseline in procalcitonin level at day 5 as compared to the control group. Increased levels of CRP, procalcitonin, and d-dimer have all been reported to be associated with more severe disease and the lower levels of these markers in the nVNS treated group may represent the initial impact of nVNS therapy to potentially improve the course of a patients’ COVID-19 symptoms.
In 2020, investigators with Nemechek Technologies authored a paper in the Journal of Clinical and Experimental Immunology that showed that taVNS is associated with lower mechanical ventilation and mortality in COVID-19. Researchers used the company’s Vitality Smartcable taVNS device.
Another firm responding to the pandemic is Synapse Biomedical. The Ohio firm received Emergency Use Authorization in 2020 for its TransAeris DPS diaphragm pacing system, to assist in weaning patients off of ventilators for no more than 30 days. During the COVID-19 pandemic, the surge of patients requiring prolonged mechanical ventilation has put an unprecedented demand on hospital and ICU resources. Even when their primary symptoms have stabilized, these patients are still at risk for developing ventilator-induced diaphragm dysfunction—further prolonging their ventilation.
The TransAeris system addresses this issue by conditioning a patient’s diaphragm to reduce or avoid VIDD. Models suggest the technology—which recently received CE Mark approval and is under clinical investigation in the U.S.—could reduce ventilator burden in COVID-19 patients by 26 percent, helping to free up more ventilators in a time of great demand.
“More than 2,000 patients have been successfully treated world-wide with our diaphragm, pacing technologies,” said Anthony Ignagni, president and CEO of Synapse Biomedical. “We welcome the FDA’s leadership in providing this emergency pathway to get our latest TransAeris device into the hands of clinicians so they can help as many COVID-19 patients as possible during this pandemic.”
Lungpacer Medical in Vancouver, BC received a similar EUA from the FDA for its phrenic nerve stimulation system. Lungpacer CEO, Doug Evans, stated, “This amazing honor provides a unique opportunity to help improve outcomes for many patients affected by this global health crisis.”
British firm Parasym has also shown an interest in the COVID market. A recent study conducted in partnership with the Human Waves Clinic and Université Libre de Bruxelles evaluated the company’s taVNS system in application to long COVID patients. They reported that patients showed improvements in both physiological and qualitative metrics. Significant improvements in fatigue levels, depression and clustered long COVID symptoms were seen, as well as improvements in autonomic tone and grip strength. Parasym is now working with autonomic dysfunction research centers to conduct larger randomized trials, with the aim of providing a safe and effective treatment for those suffering from long COVID.
Outside of the consortium, other investigators are pursuing research in this area. Last month, Fabio Bandini and colleagues from the University of Genoa in Italy published a paper in the Journal of Neurology, Neurosurgery, and Psychiatry that indicated that tDCS may help restore a sense of smell in patients with chronic anosmia or hyposmia related to COVID-19. In the double blind, sham-controlled study of seven patients, they found that anodal tDCS combined with olfactory training led to improvement in hyposmia or anosmia related to COVID-19.
