Studies add to picture of how COVID can affect the brain long term

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New studies on SARS-CoV-2's neurologic effects describe how even mild infections can lead to neuropsychiatric conditions by altering brain structure and function and review possible mechanisms for viral passage through the blood-brain barrier.

More anxiety, reduced ability to work

Even mild COVID-19 infections can alter brain structures and functions, leading to neuropsychiatric conditions such as anxiety, depression, fatigue, and sleepiness and undermining well-being, health, and the ability to work, according to studies presented last week at the ninth Brazilian Institute of Neuroscience and Neurotechnology (BRAINN) congress in Sao Paulo.

"Before the pandemic, Brazil was already considered one of the most anxious countries in the world, with 9% of the population reporting symptoms," Clarissa Yasuda, MD, PhD, of the State University of Campinas, the conference host, said in a press release. "Now we find higher levels of anxiety and depression in people who test positive for COVID-19."

One study presented at the conference and published in an April 24 supplement of Neurology involved analysis of magnetic resonance imaging (MRI) scans of 254 patients conducted 3 months after COVID-19 diagnosis.

The scans revealed atrophy of the brain's gray matter and cerebral hyperconnectivity in patients with long COVID. While the significance and persistence of these changes are unknown, they suggest cognitive dysfunction associated with anxiety and depression, the authors said.

Another study in the same journal issue involved analyzing answers to questionnaires completed by 607 bank workers with similar job descriptions and education an average of 200 days after COVID-19 diagnosis. Large percentages still reported memory problems (52%), fatigue (48%), and anxiety (38%).

"The economic impact of these people’s health problems is evident, underscoring the urgent need for specific treatment to reduce the loss to both the individuals concerned and society as a whole," lead author Gabriel Monteiro Salvador said in the release.

For a third, unpublished study described in the release, researchers developed a set of tests designed to measure muscle contraction and force, neuromuscular function, hand-muscle fatigability, and manual dexterity to better define the fatigue associated with long COVID.

The findings suggested motor-skill impairment among long-COVID patients with fatigue, with abnormal motor-unit force-frequency relationships in reaction tasks, although reaction time was unaffected. Participants also underperformed with their dominant hand in the Nine-Hole Peg Test compared with controls.

Crossing the blood-brain barrier

In Cell Death and Discovery last week, researchers from Shanghai Normal University and the University of Hong Kong reviewed the possible mechanisms of long COVID's effects on the brain.

The researchers proposed three routes of SARS-CoV-2 brain invasion:

  • The virus moves from the nasal cavity through the olfactory nerves to the olfactory bulb of the brain, where it enters sensory neurons.
  • High concentrations of SARS-CoV-2 in the respiratory tract cause damage that allows it to invade the blood and spread to multiple organs through overexpression of angiotensin-converting enzyme (ACE, which facilitates cell entry). The virus may cross the blood-brain barrier through ACE facilitation, disruption of the tight junctions of the blood-brain barrier, or traveling inside cells through the central nervous system.
  • SARS-CoV-2 invades the brain through the eyes and optic nerve, although the authors noted that eyes don't generally show high viral loads.

Children under 10–12 years are supposed to be [in] the most important stages for the brain development, which implicates that the effects of viral infection on children’s brains can be more destructive.

COVID-19 may also lead to brain fog by affecting different brain regions through hyperactivation of the immune response, cell death, or inflammation, the researchers said. "Various symptoms of memory impairments, including short-term memory, working memory, concentration, decision, confusion, problems with daily activities, and other related memory problems had been widely reported in COVID-19 patients," they wrote.

These memory problems, they said, may affect children more than adults. "Children under 10–12 years are supposed to be [in] the most important stages for the brain development, which implicates that the effects of viral infection on children’s brains can be more destructive," the authors wrote. "These Long-COVID symptoms, especially memory problems, can significantly affect the self-confidence and development of children in coming years."

Vaccination is the most effective method of preventing SARS-CoV-2 infection, followed by nonpharmacologic measures such as wearing masks and physical distancing, the researchers said. "Apart from vaccination and non-pharmaceutical controls, new drugs which can limit the viral transmission are urgently needed for containing SARS-CoV-2 transmission and in turn reducing the number of Long-COVID patients," they wrote.

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