Nerve damage and accumulation of immune corneal cells may be a sign of “long COVID,” a long-term syndrome that appears in some people after infection with COVID-19, suggests a new study.
These preliminary results will need to be verified with a larger group of people with long-haul COVID, or long-haul COVID-19, as they are called, an expert told Live Science. But the results hint at something scientists already suspected: Some symptoms of COVID long emerge due to damage to peripheral nerves, she said.
Long-haul COVID-19 have a wide range of symptoms, and a large proportion report neurological problems, including headaches, numbness in the body, loss of smell, and “brain fog” or difficulty thinking and to concentrate Previously reported live science. This constellation of symptoms suggests that the long COVID may in part result from damage to nerve cells in the body, said lead author Dr Rayaz Malik, professor of medicine and consultant physician at Weill Cornell Medicine-Qatar in Doha.
Related: 20 of the worst epidemics and pandemics in history
Specifically, preliminary evidence suggest this long COVID can involve damage to small nerve fibers – thin threads that branch off from specific nerve cells in the body and transmit sensory information about pain, temperature, and itching, among other sensations to the central nervous system. Small-fiber nerve cells also help control involuntary bodily functions, such as heartbeat and stool; therefore, damage to these cells can cause a wide range of symptoms.
Malik and his colleagues study the loss of nerve small fibers in people with Diabetes and neurodegenerative diseases like multiple sclerosis; they noticed that people with long COVID seem to share similar symptoms with these patients, so they decided to investigate the potential link.
Using a technique called corneal confocal microscopy (CCM), the team took snapshots of nerve cells in the cornea, the clear layer of the skin. eye which covers the pupil and the iris. The team used the non-invasive procedure to count the total number of small-fiber nerve cells in the cornea, while also assessing the length and degree of branching of those fibers. In their work with other conditions, the team found that when you find damage in the small-fiber nerves in the cornea, it often indicates that there is similar damage elsewhere in the body. “It’s like a really good barometer, almost, of nerve damage elsewhere,” Malik explained.
According to the new study, published Monday, July 26 in the British Journal of Ophthalmology, people who develop neurological symptoms after COVID-19 infection have significant nerve loss of small fibers in the cornea, compared to COVID-19 survivors without persistent neurological symptoms. Additionally, the degree of nerve fiber damage correlated with the severity of participants’ symptoms, meaning that greater nerve damage was linked to more pronounced symptoms.
The small study included 40 people who had recovered from COVID-19 between one and six months before their assessment; of the full group, 29 people had recovered from COVID-19 at least three months previously. In addition to having the corneal CT scan, each participant responded to a survey that included questions about neurological symptoms of COVID along.
They also filled out questionnaires about neuropathic pain, which can include numbness, tingling and burning sensations in the body, as well as muscle weakness, according to UC Davis Health. Another questionnaire helped researchers identify the location and severity of participants’ muscle pain; it also helped signal additional symptoms like fatigue and bowel issues, the authors noted.
Of the 40 participants, 22 had persistent neurological symptoms – including headache, dizziness and numbness – four weeks after recovering from their initial COVID-19 infections. And 13 of 29 people who had been cured for at least three months reported neurological symptoms at week 12 after infection. “It’s very clear, if you look at the graphs… people who have neurological symptoms definitely have a reduction in” small fiber nerves, unlike the other participants, ”said Malik.
The study authors also assessed 30 healthy people with no history of COVID-19 infection for comparison. They found that, compared to these 30 control participants, all of the COVID-19 survivors harbored a large number of immune cells on their corneas; more specifically, immune cells called dendritic cells that help inform the immune system about foreign invaders have appeared in unusually high amounts.
Related: 11 surprising facts about the immune system
People with persistent neurological symptoms showed an approximately five-fold increase in these dendritic cells, compared to healthy controls; those without neurological symptoms showed an increase of about twice.
“So clearly there is something, there is an immune process that is still going on,” even after the initial COVID-19 infection has cleared, Malik said. “So maybe there’s an immune trigger that’s activated and it takes a while for it to set in,” he said. And during this time, this uncontrolled immune response damages nerve cells.
The new study cannot prove that an immune response caused the observed nerve damage. However, the idea aligns with existing evidence that most of the neurological damage from COVID-19 is caused by inflammation, not by the virus directly infecting nerve cells, according to a 2020 commentary in the journal Pain.
“It’s not the infection per se, it’s the immune response it elicits,” said Dr. Anne Louise Oaklander, associate professor of neurology at Harvard Medical School and pathology assistant at Massachusetts General Hospital, who was not involved in the new study. “The infection speeds up your immune cells to start shooting, to fight the enemy, and there will be collateral damage,” she said. In this case, the small-fiber nerve cells can fall victim to friendly fire.
Oaklander added that she was “excited” by the new study because it provides evidence of small fiber nerve damage in long-lasting COVID patients. The data is useful for biomedical researchers, like Oaklander, who are trying to understand the causes of long COVID and how to treat the syndrome. However, for now, she said research isn’t necessarily providing solutions for patients.
In their article, Malik and colleagues suggest that corneal confocal microscopy could be used as a diagnostic tool to help identify people with long-term COVID – especially those with neurological symptoms. However, currently the technique is primarily used for research and is not widely available in clinical settings, Oaklander said.
The gold standard for assessing nerve damage to small fibers is to take a small skin biopsy of a patient’s leg and measures nerve endings inside, she said. Doctors can screen for symptoms of nerve damage with written surveys and neurological exams, but they currently require a skin biopsy to confirm their diagnoses. For this reason, it would be helpful if future studies of long-term COVID patients included these skin biopsies, as well as the standard questionnaires used to screen for small-fiber sensory neuropathies, Oaklander suggested. (“Neuropathy” refers to damage to the nerves that run through the body outside of the brain and spinal cord.)
For now, Malik has said his group plans to follow up with their initial group of 40 participants, to see how their corneal nerves and long COVID symptoms change over time. In addition, they plan to replicate their study in larger groups of patients to validate the results.
“People might say, ‘Well, 40 patients is not enough. ” We agree ; you need bigger studies, ”said Malik. Assuming the results can be confirmed in larger cohorts, this line of research may potentially provide useful insights into how doctors can treat the long COVID, he added. Treatments for post-infectious neuropathies exist, it’s just a matter of whether they would work for long-lasting COVID patients with small-fiber post-infectious neuropathy, and if so, how they can best be applied, Oaklander said.
Originally posted on Live Science.