New research from the Massachusetts General Hospital (MGH) and the National Institutes of Health hypothesizes nerve damage as the cause of long COVID symptoms in some people. The small study found treating patients with immunotherapies targeting the neuropathy could improve long COVID symptoms.
Scientists and doctors are continuing to grapple with the emergence of long COVID, a post-viral condition characterized by persistent symptoms of COVID-19. It is still unclear exactly what causes long COVID, how long the condition may last, and perhaps most importantly, how to treat the chronic illness.
Lead author on the new research, Anne Louise Oaklander, from the Department of Neurology at MGH, said as the acute impact of COVID-19 begins to settle around the world, it will become increasingly important to understand how to best treat long COVID. The overall prevalence of the condition is not clear, but it is suspected anywhere from 10 to 30 percent of those contracting COVID could experience symptoms that persist for longer than three months.
"This is one of the early papers looking into causes of long-COVID, which will steadily increase in importance as acute COVID wanes," said Oaklander. "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."
The small new study followed 17 patients with a variety of long COVID symptoms. The researchers evaluated the patients for a condition known as peripheral neuropathy, a type of nerve damage signaled by pain in the hands or feet, weakness, fatigue and sensory changes.
The study found 59 percent of the long COVID patients could effectively fit a clinical diagnosis of peripheral neuropathy. Even more significantly, the researchers found treating some of the patients with immunotherapies used to target inflammatory neuropathy led to improvements in symptoms.
Oaklander does point out not all patients responded to neuropathy treatments and some patients spontaneously improved without any kind of immunotherapy, so she suspects not all cases of long COVID can be characterized by this kind of nerve damage. However, it could be valuable for patients to consult with a neurologist if their symptoms are not improving.
"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," Oaklander said. "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."
The MGH finding is not the first to suggest some kind of nerve damage may be playing a role in the pathology of long COVID. Another new study set to be presented at next month’s European Congress of Clinical Microbiology and Infectious Diseases presents evidence to suggest dysfunction in the vagus nerve may be a central feature of long COVID.
The vagus nerve is the longest nerve in the human body, extending from the brain down into the heart and intestines. It plays a critical role in regulating a wide variety of crucial bodily functions, from controlling heart rate to managing digestion.
The new research initially gathered a cohort of 348 long COVID patients and found 66 percent displayed symptoms of vagal nerve dysfunction (VND). A smaller group of 22 patients with VND symptoms were closely studied and ultrasounds revealed a quarter of those patients displayed visible alterations to the vagus nerve.
The researchers hypothesize COVID-related inflammation causes vagus nerve dysfunction, which is the source of a number of long COVID symptoms including gastrointestinal problems and breathing impairments.
"In this pilot evaluation, most long COVID subjects with vagus nerve dysfunction symptoms had a range of significant, clinically-relevant, structural and/or functional alterations in their vagus nerve, including nerve thickening, trouble swallowing, and symptoms of impaired breathing,” the researchers said in a statement. “Our findings so far thus point at vagus nerve dysfunction as a central pathophysiological feature of long COVID."
Commenting on the vagus nerve research, David Strain, from the University of Exeter, said the new findings are useful but more clinical work will be needed to home in on effective ways to treat long COVID. Strain agreed that some long COVID symptoms are possibly related to the direct effects of COVID-19 on the nervous system, but he said it is unlikely all aspects of long COVID can be linked to the vagus nerve.
“It is entirely possible that people susceptible to nerve damage are at the greatest risk of developing long COVID; in this case this observation tells us little more than nerve damage is an result of COVID, this is greater in those with long COVID, and the damage is easy to detect in a long, complex nerve,” said Strain. “Treatment with agents that have been demonstrated to be efficacious against vagal nerve dysfunction may provide relief for patients, however, are unlikely to treat the underlying diagnosis, and thus patients would be at risk of rebound symptoms once treatment stops.”
The neuropathy study was published in the journal Neurology: Neuroimmunology & Neuroinflammation.
Sources: Harvard University, European Congress of Clinical Microbiology and Infectious Diseases