In laboratory experiments, the coronavirus can infiltrate neurons and other brain cells when those cells are cultured. It also can invade clumps of cells designed to replicate the structure of a brain, which scientists call organoids. Those observations suggest brains are vulnerable to invasion by SARS-CoV-2.
At least in theory. Not all brain specialists are convinced that what can happen in a petri dish occurs in sick humans.
“Frankly, I don’t think it tells us a lot about what’s going on in the brains of people who were infected with this virus,” said James E. Goldman, a neuropathologist and a colleague of Thakur and Canoll at Columbia. [COVID-19 neuropathology at Columbia University Irving Medical Center/New York Presbyterian Hospital | Brain | Oxford Academic
As that trio and their co-authors reported in the journal Brain in April, they did not find viral proteins in brain autopsies.
They detected no or low levels of viral RNA, depending on the technique used. Canoll suggested the viral genetic material they did find in the brain came from virus in the membrane that surrounds the brain, not from within the organ itself.
“This, alongside other studies, is suggestive that there’s not a florid amount of virus in the brain in patients who have died,” said Thakur, lead author of that study.
Although there wasn’t much virus to be found, the brains of people killed by the coronavirus weren’t unscathed . The Columbia researchers, looking at thin slices of brain tissue under microscopes, found two main types of problems in patients who died of covid.
First were infarctions, dead tissue surrounding blocked blood vessels, found in the brain’s gray matter. [...]
The second issue, appearing in the brainstem, cerebellum and other areas, involved swarms of immune cells. Those cells often converged around dead or dying neurons. “They’re actually attacking and eating the neurons,” Canoll said.
These immune cells, called microglia, were enlarged and had clustered in nodules, signaling inflammation, though not as severe as what pathologists see in cases of viral encephalitis. Curiously, there was no virus in the neurons being surrounded.
Still, microglia don’t act like this unless provoked.
“Something is triggering them to do that,” said immunologist Lena Al-Harthi, who studies at Rush University in Chicago how HIV affects the central nervous system. That trigger remains unknown, but Harthi suggested it could be an autoimmune response .
]...] Autoantibodies have been found in postmortem brains and the cerebrospinal fluid of covid patients , Harthi said.
It’s unclear whether the pathologies seen in these autopsies could also occur in patients with mild cases, or long-term symptoms. Goldman declined to speculate. These patients, many of whom were admitted to intensive care, had died of severe covid-19.
“This is a series of a small subset of patients, so there’s a selection issue,” Thakur said. But with that caveat and others — variants are spreading that weren’t in the initial wave of the pandemic, for example — she said the results are suggestive that the virus “isn’t entering and propagating and infecting the brain. ”
The scientists are working on a follow-up study examining the brains of patients who had covid and recovered but later died. Those observations should help settle whether brains in very sick patients resemble brains in other cases.
Compared with almost all other diseases, covid-19 has been studied with unprecedented focus. [...]
The scientists used tools not typically applied across the brain.
“We’ve already started to look at the brains of patients that don’t have covid” but died of other severe lung diseases, Canoll said. They are seeing pathological changes reminiscent of what they detected in brains from people who died of covid.
Joanna Hellmuth, a cognitive neurologist at the UCSF Memory and Aging Center, said she hears the same story repeatedly from previously healthy young adults who tell her that after even a mild case of covid: “My brain doesn’t work like it used to.”
Hellmuth said cognitive impairment is showing up in people who measure well in mood testing, suggesting their symptoms are not caused by depression or another psychiatric problem. She has seen similar patterns caused by other viruses