COVID and the brain: researchers zero in on how damage occurs (nature.com)
COVID and the brain: researchers zero in on how damage occurs
Growing evidence suggests that the coronavirus causes ‘brain fog’ and other neurological symptoms through multiple mechanisms.
How COVID-19 damages the brain is becoming clearer. New evidence suggests that the coronavirus’s assault on the brain could be multipronged: it might attack certain brain cells directly, reduce blood flow to brain tissue or trigger production of immune molecules that can harm brain cells.
Infection with the coronavirus SARS-CoV-2 can cause memory loss, strokes and other effects on the brain. The question, says Serena Spudich, a neurologist at Yale University in New Haven, Connecticut, is: “Can we intervene early to address these abnormalities so that people don’t have long-term problems?”
With so many people affected — neurological symptoms appeared in 80% of the people hospitalized with COVID-19 who were surveyed in one study
1 — researchers hope that the growing evidence base will point the way to better treatments.
Breaking into the brain
SARS-CoV-2 can have severe effects: a preprint posted last month
2 compared images of people’s brains from before and after they had COVID-19, and found loss of grey matter in several areas of the cerebral cortex. (Preprints are published without peer review.)
Early in the pandemic,
researchers speculated that the virus might cause damage by somehow entering the brain and infecting neurons, the cells responsible for transmitting and processing information. But studies have since indicated
3 that the virus has difficulty getting past the brain’s defence system — the blood–brain barrier — and that it doesn’t necessarily attack neurons in any significant way.
One way in which SARS-CoV-2 might be accessing the brain, experts say, is by passing through the olfactory mucosa, the lining of the nasal cavity, which borders the brain. The virus is often found in the nasal cavity — one reason that health-care workers test for COVID-19 by swabbing the nose.
Even so, “there’s not a tonne of virus in the brain”, says Spudich, who co-authored a review of autopsies and other evidence that was published online in April
4.
But that doesn’t mean it is not infecting any brain cells at all.
Studies now suggest that SARS-CoV-2 can infect astrocytes, a type of cell that’s abundant in the brain and has many functions. “Astrocytes do quite a lot that supports normal brain function,” including providing nutrients to neurons to keep them working, says Arnold Kriegstein, a neurologist at the University of California, San Francisco.
In a preprint posted in January, Kriegstein and his colleagues reported
5 that SARS-CoV-2 preferentially infects astrocytes over other brain cells. The researchers exposed brain organoids — miniature brain-like structures grown from stem cells in the lab — to the virus. SARS-CoV-2 almost exclusively infected astrocytes over all other cells present.
Bolstering these lab studies, a group including Daniel Martins-de-Souza, head of proteomics at the University of Campinas in Brazil, reported
6 in a February preprint that it had analysed brain samples from 26 people who died with COVID-19. In the five whose brain cells showed evidence of SARS-CoV-2 infection, 66% of the affected cells were astrocytes.
Infected astrocytes could explain some of the neurological symptoms associated with COVID-19, especially fatigue, depression and ‘brain fog’, which includes confusion and forgetfulness, argues Kriegstein. “Those kinds of symptoms may not be reflective of neuronal damage, but could be reflective of dysfunctions of some sort. That could be consistent with astrocyte vulnerability.”
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