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Newspaperman Liu Yadong A
Source: Ten Point Science
Author: Lu Xiuyuan
A growing body of research has found that the coronavirus may affect the brain in a number of ways. The understanding of it will directly determine the direction of subsequent treatment and drug development.
Author | Lu Xiuyuan [Japanese] Institute of Frontier Immunology, Osaka University
The COVID-19 pandemic is still spreading rapidly, and as of August 17, 2021, it has caused more than 200 million infections and more than 4.4 million deaths worldwide, and more than 24 million people have been confirmed so far. It is easy to see that the number of people recovering is also close to 200 million.
The responses of those who have recovered vary, and based on the sheer size of patients, their diversity in secondary symptoms has also been magnified to a level that cannot be ignored.
Recently, researchers in many countries have preliminarily elucidated the possible pathways of the new crown virus's impact on the nervous system through research on COVID-19 patients and recovered people. Growing evidence suggests:
Even if the coronavirus has been completely removed from the body, its effects may still be hidden deep in the brain, and in more than one way.
The coronavirus affects the nerves and causes a variety of symptoms
Previous studies have shown that in addition to the classic respiratory symptoms, the main symptoms and sequelae of new crown pneumonia are: fatigue, muscle fatigue, olfactory disorders, hair loss, palpitations and joint pain.
These symptoms are relatively explicit, and patients can easily tell whether their physical condition has changed before and after the illness. However, a significant number of people report that they experience neurological symptoms such as attention loss, memory loss, and sleep disturbances during the course of the disease and even after recovery.
These phenomena are relatively inconspicuous, and many times it is difficult for patients to say whether the symptoms are real. The incomprehension from others is even more exhausting: is it a psychological effect? Look at putting you squeamish. Is it pretending to be sick and not wanting to study well?
Some neurological symptoms are thought to be psychological. | the idea of a worm
According to the statistical conclusions of people recovering from COVID-19 in various countries around the world, about 20% of recovered patients complained that there were various forms of weakened nervous system function. Most of them will gradually disappear within a few months, but some people recover well in the early stages of recovery, suddenly attack in the middle, and some of them have not completely got rid of the sequelae of the nervous system even half a year later.
Such symptoms have a specific term in medicine and health science, called "brain fog", from the English word brainfog, which vividly describes the state of "the brain seems to be covered with a thin fog, becoming hazy".
Although there are no clear physiological indicators at this stage to determine the presence or absence of brain fog, or to define the degree of brain fog, the concept of brain fog has been widely accepted by the medical community. In addition to the new crown, many other diseases can also cause brain fog, for example, a considerable proportion of cancer chemotherapy patients will have brain fog.
There are a lot of COVID-19 patients plagued by brain fog, and Hollywood actress Alyssa Milano is one of them. She fell ill with COVID-19 last year, and although she eventually recovered, the symptoms of brain fog affected her life for a long time. In an interview last October, she briefed the public on her journey from illness to recovery.
Alyssa Milano | web image
"The first sequelae I experienced after I was discharged from the hospital was stomach pain, which was very strange and I had never had a similar experience. For the next three days or so, I never seemed to be so tired and exhausted. Later I started to lose my hair severely, which was especially painful for an actor. Until now, I have been discharged from the hospital for five months, but my body still does not seem to have fully recovered. In addition to the above symptoms, the one that pains me the most is the brain fog. I still have a hard time concentrating, often lose sleep, and occasionally forget what I was supposed to do. ”
Similarly, there are many reports of the long-term impact of brain fog on COVID-19 survivors. For example, some adolescents with excellent grades before the disease found that their cognitive function decreased significantly for a period of time after recovery. This has taken a toll on their performance in school.
A 15-year-old teenager said in an interview with reporters that he did not know whether his grades could return to the level of honor students. "If the grades can't improve as soon as possible, I feel very scared when I think about it, and I don't want to go through such pain again."
Brain fog affects a person's cognitive function. | the idea of a graphworm
The brain is not easily invaded, but occasionally it can be confused
Theoretically, almost all infectious diseases can invade the brain. Pathogens circulate throughout the body with blood circulation and, once infected with the central nervous system, are likely to cause life-threatening symptoms.
However, as the most valuable organ of the body, the brain will never sit still. Tens of millions of years of biological evolution have designed a sophisticated set of defense mechanisms for our brains. That is the "blood-brain barrier".
It is like a golden bell hood, acting as the gatekeeper of the brain.
The blood-brain barrier is essentially a special network of capillaries.
Capillaries in our body, generally act as a material transport terminal, on the one hand, to transport nutrients to all parts of the body, on the other hand, the waste of cellular metabolism is recycled into the blood circulation system. They are like courier stations on the street, which can deliver goods and collect goods. But their inspection standards for goods are not high, and sometimes some "contraband" also fish in muddy waters. The vast majority of pathogens, even cancer cells, can infect healthy tissues through capillaries.
The blood-brain barrier in the brain is composed of a more tightly arranged capillaries of endothelial cells and peripheral glial cells. It allows oxygen, water, glucose, and other nutrients necessary for the brain to pass freely (water-soluble molecules such as alcohol can also drill holes), but it will prevent bacteria and most toxic substances from invading the brain.
It is like a more professional courier station, not only making clear provisions for packages that are allowed to be delivered, but also strictly inspecting and resolutely preventing the flow of contraband to the brain.
The blood-brain barrier provides special protection for the brain from entering and leaving all kinds of macromolecules. | xvivo.com
The blood-brain barrier is trustworthy in the vast majority of situations. But unfortunately, it's not perfect.
First, its "checking" mechanism is so rigid that some of the substances we expect to deliver to the brain will also be intercepted by it. For example, some drugs used to protect the body's immune cells, or some drugs used to treat brain diseases. This is why brain diseases are very difficult to treat.
In addition, its defense line is not impregnable, and some pathogens or "abnormal" molecules also have the method of "confusing and passing".
There are two kinds of tricks for pathogens to break through the blood-brain barrier, one is a "physical" attack, that is, a hard break, and the other is a "magic" attack, which can be considered a disguised attack.
Physical attacks are most typical of rabies viruses and various encephalitis viruses. They can break through the blood-brain barrier under certain conditions, then infect brain tissue, and multiply in this place where immune strength is difficult to reach, directly destroying the human central nervous system. Therefore, to deal with such diseases, we need to try to block their breakthrough of the blood-brain barrier in advance. Once the virus enters the brain, it will be very tricky, and ordinary treatments will be difficult to work. For example, the rabies virus, once it enters the central nervous system, almost means 100% death.
While the blood-brain barrier protects the brain, it has also become an obstacle to the treatment of encephalopathy.
The picture shows the rabies virus. | Shutterstock
Fortunately, this virus is only a minority, and the new crown virus does not have such a skill. However, since it can cause neurological symptoms such as brain fog, it must mean that it can act on the brain in some form. This is one of the areas of focus of the current medical community and the focus of a series of new studies mentioned in this article.
Magic attack, new coronavirus trick negative damage
In the early days of the epidemic, researchers speculated that the new crown virus may somehow enter the brain and infect neurons, causing brain damage.
For example, some scientists believe that the new coronavirus may enter the brain through the olfactory mucosa adjacent to the brain, the inner surface of the nasal cavity. This is also the site of nasal swab sampling. But later research found that the new crown virus actually has a hard time breaking through the blood-brain barrier and multiplying in the brain, and even does not damage neurons in obvious ways.
But that doesn't mean the coronavirus can't affect brain function. New evidence suggests that covid-19 may attack the brain in a variety of ways, including direct attacks on specific brain cells, reduced blood supply to brain tissue, and induction of immune molecules that damage brain cells.
First, the coronavirus can infect a large number of functionally rich astrocytes in the brain.
This cell has a variety of functions, including providing nutrients for the normal work of neurons, and once it is violated, the neurons are also affected by it. The researchers believe this could explain some neurological symptoms, particularly fatigue, depression and brain fog. "These symptoms may not reflect damage to neurons, but they may reflect that they have some dysfunction."
Astrocytes, which provide nutrients to neurons. | Wikipedia
Second, COVID-19 can also affect the brain by reducing blood supply to the brain, disrupting the function of neurons and possibly eventually dying as a result.
For example, pericytes are special cells found in capillaries throughout the body, and researchers found that in the brain slices of hamsters, the new coronavirus inhibits the function of pericyclic receptors, causing capillaries in tissues to contract. This may result in an inadequate blood supply.
Finally, some neurological symptoms and damage are likely to come from the body's own immune system's overreaction to the new crown virus.
Some people's immune systems, after being infected with the virus, inadvertently create "autoantibodies" that attack their own tissues, triggering inflammation. For example, optic nerve myelitis will cause people to have symptoms such as vision loss and limb weakness.
There is multiple evidence that autoantibodies can cross the blood-brain barrier, which is likely to be responsible for memory impairment and psychosis. The latest research confirms that some of the new crown antibodies in the human body can bind to brain tissue, which indicates that they have the potential to damage brain tissue.
Of course, as far as the current evidence is concerned, it is not certain that these three mechanisms are correct, nor can other potential possibilities be ruled out, let alone the proportion of each mechanism.
Most researchers tend to think that all three of these mechanisms exist simultaneously in the human brain. Therefore, one of the important goals in the future is to determine the proportion of each mechanism in the final injury, which will directly determine the direction of research in treatment and drug development.
Looking back at the entire anti-epidemic process, this opponent who has entangled mankind for nearly two years is really yin and cunning. If the final study confirms that it can indeed bypass the blood-brain barrier and exert various adverse effects on the brain, then our reverence for living things may be another layer.
(Editor-in-charge Gao Peiwen)
Resources:
1. Are you suffering from 'COVID brain'? You're not alonehttps://www.smh.com.au/lifestyle/health-and-wellness/are-you-suffering-from-covid-brain-you-re-not-alone-20200923-p55yk6.html
2. 'It's frightening': Alyssa Milano details hair loss, 'brain fog' due to COVID-19 https://www.usatoday.com/story/entertainment/celebrities/2020/10/09/alyssa-milano-covid-19-lingering-symptoms-hair-loss-brain-fog/5939135002/
3. Delta Strain Threat Sequelae Woes Latest Report https://www.nhk.jp/p/special/ts/2NY2QQLPM3/blog/bl/pneAjJR3gn/bp/paQYvZL26a/
4. Corona sequelae "Brain fog" https://www.nikkei.com/article/DGXZQOUC211RI0R20C21A4000000/ immune abnormalities involved
5. A 15-year-old described what it's like to have long COVID, from forgetting the previous day's schoolwork to sitting in the shower to avoid fainting https://www.businessinsider.in/science/news/a-15-year-old-described-what-it-was-like-to-have-long-covid-from-completely-forgetting-the-previous-days-schoolwork-to-having-to-sit-in-the-shower-to-avoid-fainting/articleshow/85193261.cms
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9. SARS-CoV-2 infects brain astrocytes of COVID-19 patients and impairs neuronal viability
https://www.medrxiv.org/content/10.1101/2020.10.09.20207464v4