How COVID can damage the brain

• "Neuro-long COVID is a very important problem in the U.S. It affects millions of people and leads to people not being able to work the way they used to, or to lose time from work," Igor Koralnik, chief of neuro-infectious diseases and global neurology at Northwestern Memorial Hospital, tells Axios.
• There's an "urgent need" to research the disorders and develop therapies, NIH's Avindra Nath and Yale's Serena Spudich wrote in a January Science perspective.
• "It's the third-most frequent neurological condition in the U.S. today," says Koralnik, who started a long COVID clinic in May 2020 that's treated about 1,200 patients.

How it works

Some of the big questions researchers are trying to answer: if and how the virus is breaching the protective blood-brain barrier, how it is damaging the brain, and if the effect is permanent.

• Most of the accumulated data so far is based on adults, so there's less known about how the virus affects the brains of older teens or children and infants.

Accessing the brain: The blood-brain barrier often prevents many germs from reaching the brain, but certain pathogens are able to breach it.

• Whether SARS-CoV-2 has the ability to directly cross that barrier remains in question, although recent studies indicate it can.
• Autopsies have also found SARS-CoV-2 infections in cells near the brain can inflame the brain-barrier cells and that this inflammation can be relayed into the brain's neurons and glial cells.
• Koralnik's team published a study this week that found biomarkers in blood plasma that suggest the brain's supportive glial cells are activated — indicating there is inflammation — and neurons were found to be damaged in both long COVID patients who'd had mild disease and those who had been hospitalized with severe symptoms.

Tracking damage: Some MRI studies link brain lesions to the virus, although those were not found in all patients.

• A study of 785 people aged 51 to 81 published this week in Nature indicates COVID can shrink the size of the brain, so that months after infection some people show as much as a decade of normal aging.
• People infected with even mild cases showed cognitive decline, degeneration in parts of the brain, and brain shrinkage, says co-author Anderson M. Winkler, senior associate scientist at the National Institute of Mental Health.
• Comparing MRI scans before and after the pandemic started, infected participants "may have lost 2.9% gray matter in a given brain region, whereas non-infected participants will have lost only 0.9% over the same three-year period," Winkler tells Axios.

• "The data available for the study doesn't allow us to indicate a specific mechanism for the effects observed; these can be because the virus invades the brain, or because of the inflammation it causes," Winkler adds.

Long-term implications: Whether this damage is permanent is unknown as the brain has a remarkable ability to recover or compensate for certain damage.

• But, there is some concern it might accelerate or trigger early Alzheimer's or Parkinson's diseases.
• A JAMA Neurology study out this week followed 1,438 COVID survivors and 438 uninfected people from Wuhan, China, all 60 or older, for more than a year. They found a "markedly higher" risk of dementia in those who had experienced severe COVID. The risk appears to increase for those with mild symptoms as well.
• But Winkler says there's still much unknown. "Small previous studies using functional imaging seem to indicate improvement over time" of brain function, he says.

What's next: NIH and others are working to determine if the changes are reversible, if they affect younger individuals the same as older ones, if changes in the brain are directly related to the brain fog people experience, and what the best therapeutic options will be.

Go deeper:

• COVID linked to brain damage in scent areas
• Axios-Ipsos poll indicates long COVID prevalence
• Long COVID leaves patients and researchers in a maze of questions

Editor's note: This story originally published on March 10.