Randomized Study of Non-Invasive Autonomic Neuromodulation for Long COVID Published Online in Neuromodulation

Rhea-AI Summary

electroCore (Nasdaq: ECOR) announced online publication in Neuromodulation of a randomized study evaluating non-invasive nerve stimulation for Long COVID. The four-week study compared cervical vagus nerve stimulation, Sonocea’s acoustic stimulation, their combination and monitoring alone. Of 541 enrolled participants, 250 met final analysis criteria.

Depressive symptom scores decreased approximately 33% with electroCore’s technology, 31% with Sonocea’s and 34% with both, versus approximately 2% with monitoring alone. Each active group improved significantly from baseline; changes over time differed significantly across groups. Active treatments also showed improvements across other symptom domains. Direct comparisons found no significant differences among active treatments. Findings are hypothesis-generating: the study was open-label, lacked a sham control and relied primarily on patient-reported outcomes.

Positive

• Minor pointDepressive symptom scores fell approximately 33% with electroCore stimulation versus approximately 2% with monitoring alone.
• Minor pointActive interventions showed improvements in fatigue, cognition, breathing and other Long COVID symptom measures compared with monitoring alone.
• Minor pointCombined treatment was associated with approximately 39% lower PTSD-related symptom scores, versus approximately 6% higher with monitoring.

Negative

• Minor pointFinal analysis included 250 of 541 participants, requiring complete outcomes and at least 50% adherence for active treatments.
• Minor pointThe open-label study lacked a sham control; participants’ treatment expectations were not assessed.
• Minor pointOutcomes were primarily patient-reported, without objective physiological measures of autonomic function.
• Minor pointStatistical analysis included no correction for multiple comparisons, limiting interpretation of the hypothesis-generating findings.
• Minor pointDirect active-treatment comparisons showed no statistically significant differences, including PTSD symptoms; combination superiority was not established.

News Explained

The study is now published, but neither electroCore’s cervical stimulation nor Sonocea’s acoustic technology is FDA-cleared or approved for Long COVID, and their safety and effectiveness for that use have not been established; publication is not treatment authorization.

Key Figures

Participants enrolled: 541 participants Final analysis population: 250 participants Depressive symptom score change: Approximately 33%, 31%, and 34% decreases vs. approximately 2% +2 more

Participants enrolled

541 participants

Randomized study

Final analysis population

250 participants

Met final analytic criteria

Depressive symptom score change

Approximately 33%, 31%, and 34% decreases vs. approximately 2%

tcVNS, SAT, and combined groups, respectively, versus monitoring-only control

Within-group improvement

p < 0.001

Each active intervention; changes over time also differed across the four groups

PTSD-related symptom score change

Approximately 39% reduction vs. approximately 6% increase

Combined intervention versus monitoring-only group

Key Terms

transcutaneous cervical vagus nerve stimulation, open-label, sham control, primary endpoint

4 terms

transcutaneous cervical vagus nerve stimulation medical

"transcutaneous cervical vagus nerve stimulation (tcVNS) using proprietary electroCore technology"

A non‑invasive therapy that delivers controlled electrical pulses through the skin of the neck to stimulate the cervical branch of the vagus nerve. Devices use surface electrodes or a handheld applicator placed on the neck; stimulation alters nerve signaling to the brainstem and autonomic nervous system and is used to modulate physiological and neurological pathways. It is distinct from implanted vagus nerve stimulators and from transcutaneous stimulation applied at the ear, and its effects depend on electrode placement and stimulation settings, which can limit depth and consistency of nerve activation compared with surgical implants.

open-label medical

"These results come from an open-label study without a sham control"

Open-label describes a situation where everyone involved in a study or process knows the full details, such as who is receiving a treatment or intervention. For investors, understanding whether a project or product is open-label helps gauge the level of transparency and potential biases, influencing trust and decision-making. It’s like knowing whether a test or experiment is conducted openly or behind closed doors.

sham control medical

"an open-label study without a sham control"

A sham control is a fake version of a medical procedure or device used in clinical trials that looks and feels like the real treatment but omits the active therapeutic element. It acts like a placebo for surgeries or devices, helping researchers distinguish true medical benefit from effects driven by patient expectation or the procedure itself; investors watch for sham-controlled trials because they provide stronger evidence of effectiveness and reduce regulatory and commercial risk.

primary endpoint medical

"The primary endpoint was change in domains from the Symptom Burden Questionnaire"

The primary endpoint is the single main result a clinical study is designed to measure to decide if a treatment works, like the finish line in a race that tells you who won. Investors care because meeting or missing this goal drives regulatory decisions, future sales expectations and stock value — it turns trial data into a clear yes-or-no signal about a drug’s commercial prospects.

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Randomized, open-label, hypothesis-generating study (541 participants enrolled; 250 met final analysis criteria) evaluated two proprietary non-invasive neuromodulation technologies, electroCore’s cervical vagus nerve stimulation and Sonocea Sonic Augmentation Technology™ (SAT)

ROCKAWAY, N.J., Nov. 12, 2026 (GLOBE NEWSWIRE) -- electroCore, Inc. (Nasdaq: ECOR) (“electroCore” or the “Company”), a bioelectronic technology company, today announced that results from a randomized, open label-controlled study evaluating non-invasive autonomic neuromodulation in adults with Long COVID have been published online in Neuromodulation: Technology at the Neural Interface.

The study, “Non-invasive Autonomic Regulatory Interventions for Long COVID: A Randomized Controlled Trial,” evaluated two non-invasive approaches designed to influence autonomic regulation: transcutaneous cervical vagus nerve stimulation (tcVNS) using proprietary electroCore technology and Sonocea Sonic Augmentation Technology™, a proprietary acoustic neuromodulation technology. The study evaluated each intervention independently as well as the combination of the two approaches.

Long COVID Represents a Major Unmet Medical Need

Long COVID has emerged as one of the most consequential chronic health challenges resulting from the COVID-19 pandemic. A 2024 review published in Nature Medicine¹ estimated that approximately 400 million people worldwide have experienced Long COVID, highlighting the extraordinary scale of this persistent global health problem.

The condition can persist for months or years and may involve multiple organ systems, with patients reporting fatigue, cognitive dysfunction or “brain fog,” sleep disturbance, shortness of breath, pain, cardiovascular symptoms, anxiety, post-traumatic stress symptoms, and autonomic dysfunction. In the United States, millions of adults continue to report Long COVID, and a substantial proportion of affected individuals report limitations in their daily activities.

The burden extends well beyond individual patients. Long COVID has been associated with impaired ability to work, increased healthcare utilization, reduced quality of life, and substantial economic losses. The same Nature Medicine review estimated the annual global economic impact as approaching approximately $1 trillion, while a separate U.S. economic analysis estimated the total societal cost of Long COVID in the United States at approximately $3.7 trillion,² reflecting reduced quality of life, lost earnings, and increased medical spending.

Despite the enormous number of people affected and extensive research efforts, treatment options remain limited. There is currently no FDA-approved therapy specifically for Long COVID as a condition, and clinical management remains largely directed toward individual symptoms and associated conditions. This substantial unmet need underscores the importance of investigating new therapeutic approaches capable of addressing the complex, multisystem nature of Long COVID.

Randomized Study of Autonomic Neuromodulation

The four-arm randomized study enrolled 541 participants, 250 of whom met the final analytic criteria (complete outcome data and, for active-intervention participants, at least 50% adherence). It compared electroCore’s cervical non-invasive vagus nerve stimulation (tcVNS), SAT, combined tcVNS plus SAT, and a monitoring-only control over four weeks. SAT was delivered through headphones using a smartphone-based protocol for 15 minutes twice daily; tcVNS consisted of two 2-minute stimulations twice daily.

Across the study, the active intervention groups demonstrated improvements across multiple Long COVID symptom domains compared with monitoring alone. Improvements were observed in measures encompassing fatigue, breathing, cognition, sleep, mental health, circulation and the impact of symptoms on daily life.

Depressive symptom scores decreased by approximately 33% with electroCore’s cervical non-invasive vagus nerve stimulation, 31% with Sonocea’s Sonic Augmentation Technology, and 34% with the combination, compared with approximately 2% in the monitoring-only control group; each active intervention demonstrated a statistically significant within-group improvement (p < 0.001) and the change over time differed significantly across the four study groups. The combined intervention was associated with an approximately 39% reduction in PTSD-related symptom scores, compared with an increase of approximately 6% in the monitoring-only group. However, direct comparisons among the three active intervention groups did not show statistically significant differences, including on PTSD-related symptoms, and the study does not establish superiority of the combined intervention.

Improvements were also observed in fatigue, cognitive symptoms, breathing, and other measures of Long COVID symptom burden.

These results come from an open-label study without a sham control and are considered hypothesis-generating; key limitations are described below.

“Long COVID represents an enormous unmet medical need,” said Peter S. Staats, M.D., MBA, Chief Medical Officer and Co-Founder of electroCore and lead author of the study. “Millions of people continue to experience symptoms that can affect multiple aspects of their health and their ability to work and function, yet we still have no FDA-approved therapy specifically for Long COVID as a condition. That makes the search for new therapeutic approaches particularly important.

What makes these findings especially interesting is that we evaluated two distinct, non-pharmacologic approaches to autonomic neuromodulation—direct cervical non-invasive vagus nerve stimulation and a novel acoustic intervention—and observed improvements across multiple symptom domains. Long COVID is unlikely to have a single cause or a single solution, but these results suggest that autonomic regulation may represent a potential therapeutic target worthy of further investigation in larger, sham-controlled studies.”

The study was conducted remotely in adults with symptoms persisting at least three months following COVID-19 infection. Participants were randomized to monitoring alone, SAT, cervical tcVNS, or combined SAT and tcVNS. The primary endpoint was change in domains from the Symptom Burden Questionnaire for Long COVID (SBQ-LC), with additional validated, self-reported measures assessing anxiety, depression, post-traumatic stress symptoms, autonomic symptoms, and self-reported biobehavioral state.

The investigators noted several limitations, including the open-label design, absence of a sham-stimulation control, reliance primarily on patient-reported outcomes, the absence of objective physiological measures of autonomic function, the facts that participants’ treatment expectations were not assessed, participant attrition, and the absence of correction for multiple comparisons. Accordingly, the findings are considered hypothesis-generating and warrant confirmation in future sham-controlled studies incorporating objective physiological measures and longer follow-up.

The study was funded by the Defense Threat Reduction Agency (DTRA) of the U.S. Department of Defense, which had no role in data analysis, interpretation, manuscript preparation or the decision to publish the study results. The views expressed in this release are those of the authors and the Company and do not necessarily reflect the official policy or position of the Department of Defense or the U.S. Government, and no endorsement should be inferred. Participant monitoring, randomization, data collection and database management were conducted by Leidos, an independent third party. Dr. Staats is a co-founder and Chief Medical Officer of electroCore, and co-author Stephen W. Porges, Ph.D., is a founder of Sonocea.

A Potential New Therapeutic Direction

Long COVID is increasingly understood as a heterogeneous, multisystem condition that may involve interacting immune, inflammatory, vascular, metabolic, neurological and autonomic mechanisms. This complexity may help explain why finding a single effective pharmacologic treatment has proven difficult.

The authors hypothesized that interventions capable of influencing autonomic regulation through different pathways could provide another approach to addressing the broad symptom burden experienced by some patients. Cervical non-invasive vagus nerve stimulation is intended to engage the vagus nerve in the neck, while SAT uses patterned auditory stimulation intended to influence central neural networks involved in autonomic regulation.

The observation that both approaches were associated with improvements provides support for further investigation of autonomic neuromodulation as an investigational, non-pharmacologic therapeutic strategy for Long COVID.

Neither electroCore’s cervical non-invasive vagus nerve stimulation nor Sonocea Sonic Augmentation Technology (SAT) has been cleared or approved by the FDA for the treatment of Long COVID. The safety and effectiveness of the technologies for Long COVID have not been established.

About electroCore, Inc.
electroCore, Inc. is a bioelectronic technology company whose mission is to improve health and quality of life through innovative non-invasive bioelectronic technologies. The Company’s two leading prescription products, gammaCore® non-invasive vagus nerve stimulation (nVNS) and Quell® neurostimulator, treat chronic pain syndromes through non-invasive neuromodulation technology. Additionally, the company commercializes its handheld, and personal use Truvaga™ and TAC-STIM™ nVNS products utilizing bioelectronic technologies to promote general wellness and human performance. Truvaga™ and TAC-STIM™ are not intended to diagnose, treat, cure, mitigate or prevent any disease or condition, including Long COVID.

For more information, visit www.electrocore.com.

About Sonocea Inc.
Sonocea Inc. is a neuroscience technology company developing non-invasive acoustic neuromodulation approaches to support autonomic nervous system regulation. Its proprietary Sonic Augmentation Technology™ (SAT) uses a novel signal-generation architecture to create structured acoustic interventions delivered through ordinary headphones or speakers.

References
Cutler DM. The Costs of Long COVID. JAMA Health Forum. 2022;3(5):e221809. doi:10.1001/jamahealthforum.2022.1809

Al-Aly Z, Davis H, McCorkell L, et al. Long COVID science, research and policy. Nature Medicine. 2024;30:2148–2164. doi:10.1038/s41591-024-03173-6

Staats PS, Dana AN, Lawrence T, Porges SW. Non-invasive autonomic regulatory interventions for Long COVID: a randomized controlled trial. Neuromodulation: Technology at the Neural Interface. 2026. doi: 10.1016/j.neurom.2026.09.025.

Forward-Looking Statements

This press release and other written and oral statements made by representatives of electroCore may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include, but are not limited to, statements regarding the potential implications of the study described in the release and of future research involving non-invasive vagus nerve stimulation or acoustic neuromodulation for Long COVID; the possible design, conduct or results of any future studies; the possible development, regulatory review or commercialization of technologies or products for Long COVID and other indications; the Company’s future business strategies, growth opportunities, prospects, product development and market expansion; and other statements that are not historical in nature, particularly those using terms such as “anticipates,” “will,” “expects,” “believes,” “intends,” “may,” “potential” and similar expressions.

Actual results could differ materially from those projected in any forward-looking statement because of numerous factors, including the preliminary, hypothesis-generating nature of the findings described in this release; the open-label design of the study, the absence of a sham-stimulation control, the absence of objective physiological measures, reliance primarily on patient-reported outcomes, participant attrition and the absence of correction for multiple comparisons; the risk that future studies may not confirm these findings; the need for additional analysis and replication; uncertainties inherent in developing new products, technologies, or indications; the Company’s ability to obtain any required regulatory clearances or approvals for new products, including for Long COVID; the Company’s dependence on third parties, including Sonocea, for technologies evaluated in the study; the ability to commercialize products; the performance, adoption and market acceptance of non-invasive vagus nerve stimulation products; electroCore’s results of operations and financial performance; inflation and currency fluctuations; competition in the industry; and overall economic and market conditions.

Forward-looking statements speak only as of the date of this press release. electroCore assumes no obligation to update any forward-looking statement or the reasons actual results could differ from those projected, except as required by law. Investors should review the information in this release together with the risk-factor disclosures in electroCore’s reports and other documents filed with the U.S. Securities and Exchange Commission at www.sec.gov.

Contact:
ECOR Investor Relations
(973) 302-9253
investors@electrocore.com

---

¹ Al-Aly Z, Davis H, McCorkell L, et al. Long COVID science, research and policy. Nature Medicine. 2024;30:2148–2164. doi:10.1038/s41591-024-03173-6.
² Cutler DM. The economic cost of Long COVID: An update. Harvard University. 2022. https://scholar.harvard.edu/files/cutler/files/long_covid_update_7-22.pdf 

FAQ

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What did electroCore’s Long COVID study show about depressive symptoms?

Depressive symptom scores decreased approximately 33% with electroCore’s cervical vagus nerve stimulation, compared with approximately 2% in the monitoring-only group. Scores decreased 31% with Sonocea’s acoustic technology and 34% with combined treatment. Each active group showed statistically significant within-group improvement (p < 0.001), but direct comparisons among active treatments showed no statistically significant differences.

Are electroCore’s and Sonocea’s technologies FDA-approved for Long COVID?

Neither electroCore’s cervical non-invasive vagus nerve stimulation nor Sonocea’s Sonic Augmentation Technology has been FDA-cleared or approved for Long COVID. Their safety and effectiveness for this condition have not been established.

Who funded and managed electroCore’s Long COVID study?

The Defense Threat Reduction Agency funded the study, and independent third party Leidos handled participant monitoring, randomization, data collection and database management. The agency had no role in analysis, interpretation, manuscript preparation or the publication decision. Lead author Peter Staats is electroCore’s co-founder and chief medical officer; co-author Stephen Porges is a Sonocea founder.