[김길원의 헬스노트] “Corona 19, the second pandemic fights aftereffects”

“Headache and fatigue are due to blood vessel damage, not brain infection”… Dr. Myung-Hwa Lee, NIH, USA, dissertation at NEJM

US ships pay attention to research on chronic fatigue syndrome after infection… “An autopsy is essential to understanding the new infectious disease”

(Seoul = Yonhap News) Reporter Gil-won Kim = “After vaccination against the new coronavirus infection (Corona 19), the world will gradually escape from fear of infection. However, it is not over, it is a new beginning. Now, we must fight the aftereffects of Corona 19 in earnest. We must prepare for the’second pandemic'”

NIH neuroscientist Dr. Myung-Hwa Lee (52), who is participating in a study of “post-infectious encephalomyelitis and chronic fatigue syndrome” led by the National Institutes of Health (NIH), emphasized that vaccination is important, but research to overcome the aftereffects of COVID-19 should be hurried. did.

Dr. Lee received global attention for his brain autopsy results of patients who died of Corona 19 in the latest issue of the international academic journal’New England Journal of Medicine’ (NEJM). Dr. Lee participated as the first author of this paper.

In the paper, the research team presented the results that neurological symptoms such as headache, fatigue, and vomiting caused by Corona 19 infection were not caused by viral infection of the brain tissue itself, but to blood vessel damage caused by a wide range of inflammatory reactions in the body. This is considered the first result of confirming how the Corona 19 virus affects the brain based on an autopsy.

In order to hear detailed research results and overall opinions on Corona 19, I had time to ask and answer several times with Dr. Lee via email and social network (SNS).

The following is a question and answer with Dr. Lee.

A, C, and F are magnetic resonance microscopy (MRM) photographs of brain tissue, and B, D, and E show evidence of brain microvascular damage by immunofluorescence staining.  If you look closely at the basement membrane of the blood vessel in the B2 picture, you can see that there is no leakage of fibrin sources around the intact base layer, but plasma proteins have diffused into the tissue around the thin base layer (arrow).  This indicates that components that should be in the blood vessels have leaked from the damaged blood vessel to the brain parenchyma.  When blood vessels are damaged, immune cells, such as mononuclear cells and lymphocytes, and plasma proteins in the blood vessels leak into the brain parenchyma, resulting in inflammatory reactions and various pathological reactions.  These microvascular damages were found in 10 of 13 patients who took MRM images.  The G~N photographs are pathological findings observed in the brain parenchyma, showing that microglial cells are clustered together to form damaged neurons and are groping.  These findings are a clue that not only the respiratory failure of COVID-19 patients is due to a direct infection of the virus to the lung tissue, but also the deterioration of brain cell function in the respiratory center of the brain. [이명화 박사 제공]

A, C, and F are magnetic resonance microscopy (MRM) photographs of brain tissue, and B, D, and E show evidence of brain microvascular damage by immunofluorescence staining. If you look closely at the basement membrane of the blood vessel in the B2 picture, you can see that there is no leakage of fibrin sources around the intact base layer, but plasma proteins have diffused into the tissue around the thin base layer (arrow). This indicates that components that should be in the blood vessels have leaked from the damaged blood vessel to the brain parenchyma. When blood vessels are damaged, immune cells, such as mononuclear cells and lymphocytes, and plasma proteins in the blood vessels leak into the brain parenchyma, resulting in inflammatory reactions and various pathological reactions. These microvascular damages were found in 10 of 13 patients who took MRM images. The G~N photographs are pathological findings observed in the brain parenchyma, showing that microglial cells are clustered together to form damaged neurons and are groping. These findings are a clue that not only the respiratory failure of COVID-19 patients is due to a direct infection of the virus to the lung tissue, but also the deterioration of brain cell function in the respiratory center of the brain. [이명화 박사 제공]

– I know that the corona19 vaccine is in full swing in the United States, but did you get the vaccine?

▲ A few days ago, I finished the 2nd dose of modder or vaccine.

– Are there any aftereffects?

▲ After the 2nd vaccination, I was lying down for two days because I felt cold. There are individual differences after the COVID-19 vaccination, but there seems to be a more difficult person. Compared to the general influenza vaccine, the body ache was worse. In particular, the arm on the side of the vaccine was a little difficult to move, and there was a headache. My older sister (nurse) received the Pfizer vaccine, but the symptoms were similar.

– According to the paper, is the Corona 19 virus not directly penetrating the human brain?

▲ Right now. This means that neurological symptoms such as headache and chronic fatigue are more likely to appear as damage to related blood vessels due to a wide range of inflammatory reactions in the body, not as an infection of the brain tissue itself.

– Is there an opportunity to focus specifically on brain research?

▲ Since the pandemic, almost all researchers focus on organs that are primarily targets of viruses, such as the lungs, and forget about the brain. However, our research team saw that neuroinflammatory diseases are more prevalent and can cause more problems than they might have guessed. In fact, many patients have chronic fatigue and brain fog even after recovery, making it difficult to think clearly, and many neurological symptoms, such as decreased memory, complain of experiences lasting weeks to months. In serious cases, they may complain that they greatly interfere with daily life.

Autopsy brain tissue of corona19 death patient [이명화 박사 제공]

Autopsy brain tissue of corona19 death patient [이명화 박사 제공]

– The common coronavirus that causes influenza does not penetrate the brain tissue. Is it different?

▲ Coronavirus usually causes animal diseases, but seven coronaviruses (HCoV), including SARS and MERS, are known to infect humans. All of these human coronaviruses cause neurological complications. The particles and genomic sequences of the SARS virus have already been detected in the brain tissues of patients with SARS.

– Then, can the corona 19 virus have a significantly different infection route from SARS and MERS?

▲ Since the corona 19 virus belongs to the beta corona virus along with SARS and MERS, there are many opinions that it also penetrates the brain and appears to have various neurological symptoms. This is the background for the (research team) to question exactly how the Corona 19 virus affects the human brain. However, none of the autopsied brain tissue was virus-free.

– Please explain in detail the research method and results.

▲ The brain tissues of 19 patients (5 to 73 years old) in the United States who died from Corona 19 infection were autopsied. Using a high-power MRI scanner that is 10 times more sensitive than normal magnetic resonance imaging and can be photographed at a microscope level, the olfactory bulb of the brain that controls the sense of smell and the brainstem that controls breathing and heart rate are observed with focus. did. As a result, in both areas, bright spots showing signs of inflammation and dark spots due to bleeding were seen in both areas. As a result of performing immunostaining on the same tissue, it was confirmed that the microvascular wall in the area where bright spots were visible became abnormally thin, and that fibrinogen, one of the plasma proteins, leaked into the brain parenchyma following the destruction of blood vessels. It seems that plasma proteins and immune cells (T-cells) in the blood are leaked into the brain parenchyma due to such cerebrovascular damage, activating inflammatory cells in the brain and triggering immune and inflammatory reactions in the brain. The dark spots appear to have a different pattern of clots and there is no evidence of an immune response.

– How was the virus detection test done?

▲ Several research methods (RT-PCR, RNA sequencing, RNA in situ hybridization, immunostaining) were used to test, but no virus was detected. The possibility of the virus entering the brain through several pathways, such as the bloodstream or neurotransmitters, has been raised, but this is not clear. However, pathology in the brain is understood as an inflammatory response due to microvascular damage rather than a direct effect of a virus.

– However, there have been several papers suggesting viral infection of brain tissue.

▲ Viral RNA was detected by RT-PCR in 10 of the 15 papers published so far, but the RNA copy number was very low. In addition, viral proteins were not detected in many cases, and there is controversy about the three papers that were positive. Therefore, looking at the neuropathological findings observed in the posterior tissues of the brain, it is a common opinion that several neurological symptoms appear to be’immune-mediated’ processes rather than a direct result of viral infection to the brain tissue.

NIH Dr. Myunghwa Lee [이명화 박사 제공]

NIH Dr. Myunghwa Lee [이명화 박사 제공]

– It is said that it causes similar symptoms without directly penetrating the brain tissue, but has the mechanism been identified?

▲ A follow-up study is currently underway to clarify the mechanism. Currently, it is approaching due to damage to the brain microvessels due to activation of the complement system, which is the innate immune system. We will try to make follow-up research published in the near future.

– In Korea, there is a lack of autopsy research on infected deaths. How did you secure brain tissue?

▲ We received 17 and 3 brain tissues from the New York Office of Coronation and Iowa State University, respectively. Autopsy research is essential to understanding the new disease. By closely examining the body organs including the brain of a deceased Corona 19 patient, the degree of infection of the virus and the degree of involvement of the body organs can be determined. Through this, the characteristics of the disease can be identified, and further, mechanism studies can be conducted in a more controlled form by conducting cell-level research or animal research.

– Who are the collaborators?

▲ With NIH Dr. Avindra Nas as the general manager, neuroscientists, multiple pathologists for autopsy and pathological findings, medical physicists for magnetic resonance imaging tests, and bioinformatics experts for RNA sequencing formed a team together.

– NIH’s ongoing research on chronic fatigue syndrome after infection is attracting attention. What triggered it?

▲ In 2015, NIH President Francis Collins started the study from a letter received from a former Washington Post reporter patient. However, even at the NIH, research funding has not been received and there is little research funding, so the need for research has increased as the number of patients rapidly increased in the Corona 19 situation.

– If group immunity is achieved through vaccination, will this infection sequelae be reduced?

▲ Of course, with vaccination in full swing, the infection rate, inpatient rate, and death rate in the United States are significantly decreasing day after day. I, too, escaped the fear of infection after the second vaccination. However, it is not a situation to be relieved. Rather, it seems that there is a second pandemic left to fight the aftereffects in earnest.

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