Scientists study how COVID-19 enters and damages the brain

it becomes clearer how COVID-19 damages the brain. Now new evidence published in the scientific journal Nature suggests that the coronavirus attack on the brain could have several fronts: it could directly attacking certain brain cells, reducing blood flow to brain tissue, or triggering the production of immune molecules that can damage brain cells.

Coronavirus infection SARS-CoV-2 can provoke memory loss, strokes, and other effects on the brain. The question says Serena Spudich, neurologist of the Yale University at New Haven, Connecticut, es: “Can we intervene early to fix these anomalies so that people don’t have long-term problems?”

With so many people affected (neurological symptoms appeared in 80% of people hospitalized with COVID-19 who were interviewed in a study), Researchers hope the growing evidence base will pave the way for better treatments.

Break into the brain

El SARS-CoV-2 can have serious effects: a preprint published last month against photos of people’s brains before and after COVID-19, and found loss of gray matter in various areas of the cerebral cortex. (Preprints are published without peer review).

At the start of the pandemic, researchers they speculated that the virus could cause damage by somehow entering the brain and infecting neurons, cells responsible for transmitting and processing information. But since then studies have indicated that the virus has difficulty passing through the brain’s defense system, the blood-brain barrier, and it does not necessarily attack neurons significantly.

One way for SARS-CoV-2 to access the brain, experts say, is passing through the olfactory mucosa, the mucous membrane of the nasal cavity, that borders the brain. The virus is often found in the nasal cavity, one of the reasons healthcare workers test for COVID-19 by rubbing their noses.

Even like that, “There isn’t a ton of viruses in the brain”, of Spudich, co-author of a review of autopsies and other evidence published online in April. But that doesn’t mean it doesn’t infect any brain cells.

Studies now suggest that SARS-CoV-2 it can infect astrocytes, a type of cell that is abundant in the brain and has many functions. “Astrocytes do a lot to support normal brain function,” including providing nutrients to neurons to keep them active, he says. Arnold Kriegstein, neurologist of the University of California at San Francisco.

In a prepress published in January, Kriegstein and his colleagues reported that SARS-CoV-2 preferentially infects astrocytes over other brain cells. Researchers exposed to the virus brain organoids, miniature brain-like structures that are grown from stem cells in the lab. SARS-CoV-2 almost exclusively infects astrocytes on all other cells present.

To bolster these laboratory studies, a group that included Daniel Martins-de-Souza, director of proteomics at University of Campinas in Brazil, reported in a February pre-publication that he had analyzed brain samples from 26 people who died with COVID-19. In the five whose brain cells showed signs of infection with SARS-CoV-2, 66% of affected cells were astrocytes.

“Infected astrocytes could explain some of the neurological symptoms associated with COVID-19, specially fatigue, depression and “brain fog”, which included confusion and forgetfulness ”, he argues Kriegstein. “It is possible that these types of symptoms do not reflect neural damage, but they could reflect some dysfunction. This could be consistent with the vulnerability of astrocytes. “

Astrocytes they can be vulnerable even if they are not infected with the virus. A study published on June 21 compared the brains of eight deceased people who had COVID-19 with the brains of 14 witnesses. The researchers found no trace of SARS-CoV-2 in the brains of those infected, but they did. they found that gene expression had been affected in some astrocytes, which were not functioning properly.

In view of all these findings, researchers want to know how many brain cells must be infected or damaged to cause neurological symptoms ”, of Ricardo Costa, physiologist Louisiana State University of Health at Shreveport, whose team is studying the effects of SARS-CoV-2 on brain cells.

“Unfortunately, there is probably no simple answer ”, warns Kriegstein, noting that Cells, including neurons, in some areas of the brain will cause more dysfunction than others if damaged.

Blockage of blood flow

Too Evidence has accumulated that SARS-CoV-2 can affect the brain by reducing blood flow to it, what it affects the function of neurons and ultimately kills them.

The pericitos son cells in small blood vessels called capillaries all over the body even in the brain. A February preprint reported that SARS-CoV-2 could infect pericyte-like cells in brain organoids.

In April, David Attwell, neuroscientist University College London, and his colleagues published a preprint showing evidence that SARS-CoV-2 can affect the behavior of pericytes. The researchers observed that in slices of hamster brain, SARS-CoV-2 blocks the function of receptors in the pericytes, causing tissue capillaries to contract. “It turns out it’s a big effect,” he says. Attwell.

It’s a “really cool” study, he says. Spudich. “It might be something that determines some of the permanent injuries that we see, some of these little vessel hits. “

Attwell suggests that medicines used to treat high blood pressure, which involves restriction of blood vessels, could be useful in some cases of COVID-19. Currently, two clinical trials are investigating the drug’s effect against hypertension. losartan to treat the disease.

Immune dysfunction

Too there is growing evidence that certain neurological symptoms and damage are the result of an overreaction of the body’s own immune system and even failures after encountering the coronavirus.

“Over the past 15 years, it has become clear that, in response to infection, some people’s immune systems inadvertently produce “autoantibodies” that attack their own tissues, ”he says Harald Prüss, neuroimmunologist of the German Center for Neurodegenerative Diseases in Berlin. This can cause long-term conditions such as neuromyelitis optic, in which people experience symptoms such as vision loss and weakness in limbs. In a review published in May, Prüss summarized the evidence that these autoantibodies can cross the blood brain barrier and contribute to neurological disorders ranging from memory impairment to psychosis.

This route could also work in COVID-19. In a study published last year, Prüss and his colleagues isolated antibodies to SARS-CoV-2 from people and found one that could protect hamsters from infection and lung damage. The aim was to create new treatments. But Researchers too found that some of the antibodies could bind to brain tissue, suggesting they could damage it. “Currently we are trying to demonstrate it clinically and experimentally ”, of Prüss.

In a second article, published online last December, a team that included Prüss studied the blood and cerebrospinal fluid of 11 critically ill people with COVID-19, all of whom had neurological symptoms. All of them produced autoantibodies capable of binding to neurons. “It has been proven that giving patients intravenous immunoglobulins, another type of antibody, to suppress the action of harmful autoantibodies is quite effective, indicated Prüss.

These means (astrocytes, pericytes and autoantibodies) are not mutually exclusive Yes they are probably not the only ones: People with COVID-19 are likely to exhibit neurological symptoms for a variety of reasons. Prüss emphasizes that a key question is what proportion of cases are caused by each route. “This will determine the treatment,” he says.

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