Does Nerve Damage Contribute to Long-COVID Symptoms?

Summary: Researchers report some patients with long-COVID have lasting nerve damage that appears to be caused by infection-triggered immune dysfunction.

Source: Mass General

During the COVID-19 pandemic, some people infected with the SARS-CoV-2 virus continue to experience “long-COVID” symptoms persisting at least three months after recovery from COVID, even after mild cases. These include difficulty getting through normal activities, faintness and rapid heart rate, shortness of breath, cognitive difficulties, chronic pain, sensory abnormalities, and muscle weakness.

A new study led by researchers at Massachusetts General Hospital (MGH) and the National Institutes of Health suggests that some patients with long-COVID have long-lasting nerve damage that appears caused by infection-triggered immune dysfunction.

The study, newly published in Neurology: Neuroimmunology & Neuroinflammation, included 17 patients with COVID (16 with mild cases) who met WHO criteria for long-COVID. They had been evaluated and treated in 10 U.S. states/territories.

Evaluations revealed evidence of peripheral neuropathy in 59%. Typical symptoms of neuropathy nerve damage include weakness, sensory changes, and pain in the hands and feet as well as internal complaints including fatigue.

“This is one of the early papers looking into causes of long-COVID, which will steadily increase in importance as acute COVID wanes,” says lead author Anne Louise Oaklander, MD, Ph.D., an investigator in the Department of Neurology at MGH.

This shows a man in a facemask
A new study led by researchers at Massachusetts General Hospital (MGH) and the National Institutes of Health suggests that some patients with long-COVID have long-lasting nerve damage that appears caused by infection-triggered immune dysfunction. Image is in the public domain

“Our findings suggest that some long-COVID patients had damage to their peripheral nerve fibers, and that damage to the small-fiber type of nerve cell may be prominent.”

Oaklander notes that if patients have long-COVID symptoms that aren’t otherwise explained and aren’t improving, they might benefit from discussing neuropathy with their doctor or seeing a neurologist or neuromuscular specialist.

“Research from our team and others is clarifying what the different types of post-COVID neuropathy are, and how best to diagnose and treat them,” says Oaklander.

“Most long-COVID neuropathies described so far appear to reflect immune responses to the virus that went off course. And some patients seem to improve from standard treatments for other immune-related neuropathies.” She cautioned that there hasn’t been enough time to conduct clinical trials to rigorously test specific treatments , however.

Co-authors include Alexander J. Mills, BS, Mary Kelley, DO, Lisa S. Toran MD, Bryan Smith, MD, Marinos C. Dalakas, MD, and Avindra Nath, MD.

About this COVID-19 research news

Author: Press Office
Source: Mass General
Contact: Press Office – Mass General
Image: The image is in the public domain

Original Research: Open access.
Peripheral Neuropathy Evaluations of Patients With Prolonged Long COVID” by Anne Louise Oaklander et al. Neurology: Neuroimmunology & Neuroinflammation


Peripheral Neuropathy Evaluations of Patients With Prolonged Long COVID

Background and Objectives 

Recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection appears exponential, leaving a tail of patients reporting various long COVID symptoms including unexplained fatigue/exertional intolerance and dysautonomic and sensory concerns. Indirect evidence links long COVID to incident polyneuropathy affecting the small-fiber (sensory/autonomic) axons.


We analyzed cross-sectional and longitudinal data from patients with World Health Organization (WHO)-defined long COVID without prior neuropathy history or risks who were referred for peripheral neuropathy evaluations. We captured standardized symptoms, examinations, objective neurodiagnostic test results, and outcomes, tracking participants for 1.4 years on average.


Among 17 patients (mean age 43.3 years, 69% female, 94% Caucasian, and 19% Latino), 59% had ≥1 test interpretation confirming neuropathy. These included 63% (10/16) of skin biopsies, 17% (2/12) of electrodiagnostic tests and 50% (4/8) of autonomic function tests. One patient was diagnosed with critical illness axonal neuropathy and another with multifocal demyelinating neuropathy 3 weeks after mild COVID, and ≥10 received small-fiber neuropathy diagnoses. Longitudinal improvement averaged 52%, although none reported complete resolution. For treatment, 65% (11/17) received immunotherapies (corticosteroids and/or IV immunoglobulins).


Among evaluated patients with long COVID, prolonged, often disabling, small-fiber neuropathy after mild SARS-CoV-2 was most common, beginning within 1 month of COVID-19 onset. Various evidence suggested infection-triggered immune dysregulation as a common mechanism.

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