Long COVID: Brain inflammation, cell death found in new study

• Cognitive and neurological symptoms are common in people with long COVID, and the symptoms can be debilitating for those affected.
• While growing evidence suggests that the SARS-CoV-2 virus causes damage to the central nervous system, the underlying mechanisms are not well understood.
• Now, a new study in primates has shown that SARS-CoV-2 infection causes brain inflammation and even cell death, among other forms of brain injury.

Brain fog is a term that has been coined to describe some of the cognitive effects some people can experience during and following SARS-CoV-2 infection.

Long COVID can affect 3/10 people who have COVID-19. Over three-quarters of people with the condition report cognitive or neurological symptoms for months after infection, and many find them debilitating, according to recent studies. Some researchers are coining the condition “neuro-COVID” to describe this presentation of the disease.

However, despite some recognition of the prevalence of these conditions, treating patients with these symptoms has proved challenging due to little understanding of their cause.

Now, a study published inNature Communications on the effect of SARS-CoV-2 infection on the brains of primates has revealed parallels with studies carried out on human autopsies.

Autopsy studies have been performed on human brains of people who had died from COVID-19 but the inability to distinguish between the damage caused specifically by the virus and other factors is a limitation of this research.

Lead author Dr. Tracey Fischer from the Tulane University National Primate Research Centre told Medical News Today in an interview that using an animal model had allowed researchers to measure the damage they observed was solely due to SARS-CoV-2 infection.

She said: “We have additional insight into the pathology of the disease in the brain that may be [affecting] individuals with neurological issues, during infection, as well as those who go on to experience or continue to experience these neurological issues.”

A range of brain injuries

Researchers infected 4 Rhesus Macaques and 4 African Green Monkeys with SARS-CoV-2. Two additional animals of each species were selected to act as age-matched controls. Autopsies of their brains sampled tissues from seven regions including frontal, parietal, occipital, and temporal lobes, basal ganglia, cerebellum, and brainstem.

Neuroinflammation was found to be greater in the primates with SARS-CoV-2 infection than in the controls. Researchers also discovered significantly more cell death, microhemorrhages, and signs of lack of oxygen to the brain in the monkeys that had been infected with SARS-CoV-2.

These findings were in line with previous studies that had looked at autopsies of human brains from people who had died from COVID-19. The findings could be the reason for the neurological and cognitive symptoms of COVID-19 and long COVID, the authors suggested. Dr. Fischer said: “I believe it’s our body’s response to the infection that’s largely driving this.”

She added: “When we do have a significant inflammatory event in the body, it does affect the brain. And anything [could be] causing that.”

“What was really surprising about this was, one, we saw it in animals who did not have severe respiratory disease. [Secondly,] we also saw this increase in the number of microhemorrhages in the brain — the small bleeds in the brain — and also [in] the neuronal cell death.”

This last finding was most concerning, she said, as cell death could cause “significant deficit for individuals.”

‘Brain fog’ vs. ‘brain injury’

Dr. James Jackson, director of behavioral health at the ICU recovery center at Vanderbilt University who was not involved in the research, said the findings added to the growing evidence that COVID-19 can cause brain injury.

He advocated for a move away from the term “brain fog” to describe neurological or cognitive symptoms following COVID-19. The patients he spoke to in support groups that he runs, Dr. Jackson explained, did not appreciate the term. Instead, he explained in an interview with Medical News Today:

“If people begin to think of this as a brain injury, and not just as ‘brain fog’ they’ll be more inclined to do what we do with people with brain injuries. Namely, we refer them to cognitive rehabilitation experts who can help them. […] With mild brain injuries many of these people get substantially better. […] But people don’t think necessarily of cognitive rehab for ‘brain fog.’”

– Dr. Jackson

Pointing out there were millions of survivors with long COVID, he explained there were not currently enough services to provide cognitive rehabilitation to all affected people.

“So, we need to think about innovative ways that we could try to improve cognition in these patients, because we’re clearly going to overwhelm the system very rapidly if even a small percentage of eligible patients decide to start pursuing the treatment they need. So, that’s a problem,” Dr. Jackson said.

Future research into computer-based cognitive programs could be valuable to identify accessible treatments as they are “scalable,” the researcher added.

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