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NIH renewed focus on the neurological symptoms of long COVID and ME/CFS

recent article in the journal Science suggests that COVID-19 may cause a number of neurological symptoms (including confusion, stroke and neuromuscular disorders) for people who overcome the acute illness but go on to develop long COVID.

What is most remarkable is that there appears to be very little direct evidence of viral damage to the brain and central nervous system (CNS). Many of the neurological symptoms suggest that SARS-CoV-2 (the virus that causes COVID-19) enters the CNS via the nasal cavity or across the blood–brain barrier, but analysis of cerebrospinal fluid has almost uniformly failed to detect viral RNA.

The authors, Dr Spudich, at the Yale Institute for Global Health, and Dr Nath, of the National Institute of Neurological Disorders and Stroke, write that there is an urgent need to understand better the impact of COVID-19 on the brain and CNS in long COVID patients. They also believe that the current research drive to understand long COVID may well also help patients with post-viral fatigue and ME/CFS.

Is long COVID simply another form of ME/CFS?

They point out the obvious similarities. First, that long COVID is triggered by a viral infection and that most ME/CFS patients recount some infection as being pivotal in triggering their ME/CFS. Second, many of the symptoms experienced by long COVID patients are very similar to those experienced by ME/CFS sufferers, including prolonged fatigue, post-exertional malaise, cognitive problems, sleep disturbances, and many more.

Many of these symptoms could be considered neurological, and the authors suggest that a similar immunological response to viral infection may link both long COVID and ME/CFS. We may find out that COVID-19 is just another trigger for ME/CFS.

Damage to brain tissue in long COVID

In a recent interview, Dr Nath said that while research is progressing at a rapid pace in the lab, doctors in the clinic are frustrated at not being able to offer their long COVID patients any ready solutions for their medical problems. Just as in ME/CFS, many standard blood tests return normal results.

However, he does try to reassure both sets of patients with the words: “We believe your disease. We know that you’re suffering. And we’re doing something about it.”

Hit-and-run hypothesis?

US National Institutes of Health (NIH) researchers have discovered blood vessel damage and inflammation but no sign of SARS-CoV-2 infection in brain tissue samples from COVID-19 patients who died suddenly at home, suggesting that such damage may be the result of immune responses to the virus. Other organs such as the lungs and heart showed little sign of pathological damage, and changes in the brain were the more prominent features of the disease.

Spudich and Nath’s hypothesis is that patients who go on to develop long COVID may have been healthy enough to survive COVID-19, but their brain cells have suffered enough of an insult to cause symptoms, including the types of neurological symptoms that doctors are picking up in the clinic. The key question remains whether the virus is still active, or has it set off a chain reaction of immune response that is now causing tissue damage?

Future research

Dr Nath and colleagues at the NIH plan to conduct larger-scale studies on long COVID patients. Specifically, they want to look at patients’ spinal fluid, blood and serum (plasma) for signs of either ongoing infection or immune markers. They also want to run a series of neuropsychological tests, including cognitive function, nerve conduction, heart function, autonomic function and neurotransmitters (chemicals produced by nerves to signal to each other). The aim is to understand the impact of viral infections like COVID-19 on nerves, the brain and neurological function.

How could ME/CFS patients benefit?

Dr Nath believes that prior studies on ME/CFS patients, including NIH-funded studies of neurological inflammation in ME/CFS, will guide the work of long COVID researchers and, in return, ME/CFS patients will benefit from research on long COVID that might help explain many of the cardinal symptoms of both illnesses.

There is much research on aspects of the brain and nervous system in ME/CFS to draw from, including many studies funded by ME Research UK. We also recently highlighted some of the ongoing long COVID research that is increasingly including ME/CFS patients, or comparing the two conditions, including a great many studies presented at the recent IACFS/ME International Conference.

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