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Not long ago, the "Lancet Psychiatry" magazine published a research report that found that more than 30% of COVID-19 survivors had mental health or neurological diseases, including anxiety and insomnia, as well as strokes.
, Encephalitis and other clear pathological injuries.
In particular, neurological diseases are also related to the severity of the disease in the survivors.
This has to make people think, will the new coronavirus attack the brain? At one time, researchers had speculated that the new coronavirus might enter the brain from the nose via the olfactory nerve, and found certain evidence, but this view has gradually become controversial.
Can the new coronavirus really enter the brain? Recently, a large-scale autopsy report published in the "Brain" magazine showed that the new coronavirus does not actually enter the brain directly, but the inflammation it brings can still cause more serious nerve damage! [1] This study comes from Columbia University Irvine Medical Center and New York Presbyterian Hospital.
Researchers analyzed the autopsy results of 41 patients who died in the hospital due to the new crown and found that the complete viral RNA sequence could not be detected in the patient's brain At the same time, a large number of pathological changes were observed, which may explain why patients with new coronary disease have a variety of mental and neurological diseases.
This is the largest and most detailed autopsy report of a new crown deceased ever published.
Let's take a look at these 41 compatriots who have made contributions to medicine.
The age of 41 patients ranged from 38 to 97 years old, with a median age of 74 years and generally older.
Of these, 27 (66%) were men and 34 (83%) were Hispanic/Latino.
The course of these patients also varies greatly.
8 (20%) died within 24 hours after admission, 7 (17%) died within 1 week, and 15 (37%) died within 1-4 weeks.
Eleven people (27%) died more than 4 weeks after admission.The average time from onset of symptoms to admission was 6 days (0-12 days), the average hospital stay was 19 days (0-69 days), and 24 people (59%) had been admitted to the ICU.
Complications related to the course of the patient’s hospitalization are also uncommon.
8 people (20%) developed deep vein thrombosis/pulmonary embolism (DVT/PE) during admission, 7 people (17%) had acute kidney injury requiring dialysis, and 10 people ( 24%) had sepsis.
Their brain pathological examination showed that hypoxic/ischemic injury is very common, and almost all brains have it, with varying degrees.
Acute pathology includes neuronal contraction, eosinophilia, and reactive astrocytes; subacute pathology is manifested as infarction with macrophage infiltration, reactive astrocytes, and new blood vessels.
A small number of patients (9/22%) developed multiple lesions involving the cortex, hippocampus, cerebellum, and brain.
Vascular-related pathological manifestations are also common.
Acute, subacute, or chronic infarcts were found in 18 people (44%), and 10 people (24%) had multiple small infarcts.
The researchers also found that microglia activation is also very common.
Diffuse microglia activation was found in 34 people (81%), and there were glial cell nodules in 26 people (63%), including a small number of T cell aggregations.
.
It can be seen that the microglial cells are activated but there is very little inflammation around blood vessels and lymphocyte infiltration into the brain parenchyma.
This is in sharp contrast with the tissue analysis of one of the patients with HSV-1 infection.
It can be seen that compared with HSV1 infection (below), the new crown infection has less lymphocyte infiltration.
In addition, many patients have developed pathological changes of neurodegenerative diseases, but this is not surprising considering the overall age of the patients.
Since it was previously speculated that the new coronavirus may enter the brain through the olfactory nerve, the researchers specifically checked the pathological manifestations of hydrangea and found that only a very small number of T cells and mild to moderate microglia were activated.
It can be said that the pathological manifestations are very mild.
Proportion of main pathological findings Next, the researchers used qRT-PCR to detect viral RNA in the patient’s brain, and at the same time detected the nasal epithelium as a control.
Surprisingly, the results of qRT-PCR targeting the N gene in 4 brain regions of 25 people found that the level of viral RNA in the brain is actually very low.
Almost all nasal epithelial test results were highly positive, with a median virus copy number of 43840; while the proportion of positive samples in the central nervous system and the number of virus copies were lower, 7 people (28%) were negative in all brain regions, only 9 People (36%) have multiple positive brain areas.
At the same time, viral RNA was detected in the brain area, and there is no correlation between the pathological manifestations of the tissue, which means that the pathological changes in the brain are probably not caused by the direct infection of the new coronavirus.
qRT-PCR analysis results In order to determine whether the new coronavirus can enter the brain, the researchers used RNAscope to further search for the presence of viral RNA, but no matter whether it was for the N region or the S region or a combination of the two probes, nothing was detected.
The presence of viral RNA.
This means that the new coronavirus cannot enter the brain, or their content is extremely rare, below the detection limit of RNAscope.
The researchers believe that the small amount of RNA fragments previously detected by qRT-PCR may come from circulation.
The researchers also searched for the presence of the N protein of the new coronavirus in the brain through immunohistochemistry, but also did not find it.
RNAscope detects the comparison of brain and lung tissues.
There is only one case of the patient’s brain showing perivascular infection.
In general, these findings prove that the brain damage of the new crown patient does not come from the direct attack of the new crown virus.
The main pathological manifestations can actually be divided into two The first is the damage caused by hypoxia, and the second is the attack of activated microglia on neurons (neurophagocytic phenomenon).
The former is not uncommon in the course of new coronary disease.
New coronary pneumonia itself has severe lung damage, and hypoxia can be regarded as a common pathology.
At the same time, hypoxia can further induce neurons to express signals and be engulfed by microglia.
The microglia found by the researchers mainly exist in the brainstem and are involved in the regulation of heart rate, breathing rhythm, and consciousness.
The effect on the hippocampus may affect mood and memory.
This may explain the many mental and neurological symptoms of patients with new crowns.
References: [1] Kiran T Thakur, Emily Happy Miller, Michael D Glendinning, Osama Al-Dalahmah, Matei A Banu, Amelia K Boehme, Alexandra L Boubour, Samuel S Bruce, Alexander M Chong, Jan Claassen, Phyllis L Faust, Gunnar Hargus, Richard A Hickman, Sachin Jambawalikar, Alexander G Khandji, Carla Y Kim, Robyn S Klein, Angela Lignelli-Dipple, Chun-Chieh Lin, Yang Liu, Michael L Miller, Gul Moonis, Anna S Nordvig, Jonathan B Overdevest, Morgan L Prust, Serge Przedborski, William H Roth, Allison Soung, Kurenai Tanji, Andrew F Teich, Dritan Agalliu, Anne-Catrin Uhlemann, James E Goldman, Peter Canoll, COVID-19 neuropathology at Columbia University Irving Medical Center/New York Presbyterian Hospital, Brain, 2021;, awab148, https://doi.
org/10.
1093/brain/awab148[2] The author of this articleDai Siyu
, Encephalitis and other clear pathological injuries.
In particular, neurological diseases are also related to the severity of the disease in the survivors.
This has to make people think, will the new coronavirus attack the brain? At one time, researchers had speculated that the new coronavirus might enter the brain from the nose via the olfactory nerve, and found certain evidence, but this view has gradually become controversial.
Can the new coronavirus really enter the brain? Recently, a large-scale autopsy report published in the "Brain" magazine showed that the new coronavirus does not actually enter the brain directly, but the inflammation it brings can still cause more serious nerve damage! [1] This study comes from Columbia University Irvine Medical Center and New York Presbyterian Hospital.
Researchers analyzed the autopsy results of 41 patients who died in the hospital due to the new crown and found that the complete viral RNA sequence could not be detected in the patient's brain At the same time, a large number of pathological changes were observed, which may explain why patients with new coronary disease have a variety of mental and neurological diseases.
This is the largest and most detailed autopsy report of a new crown deceased ever published.
Let's take a look at these 41 compatriots who have made contributions to medicine.
The age of 41 patients ranged from 38 to 97 years old, with a median age of 74 years and generally older.
Of these, 27 (66%) were men and 34 (83%) were Hispanic/Latino.
The course of these patients also varies greatly.
8 (20%) died within 24 hours after admission, 7 (17%) died within 1 week, and 15 (37%) died within 1-4 weeks.
Eleven people (27%) died more than 4 weeks after admission.The average time from onset of symptoms to admission was 6 days (0-12 days), the average hospital stay was 19 days (0-69 days), and 24 people (59%) had been admitted to the ICU.
Complications related to the course of the patient’s hospitalization are also uncommon.
8 people (20%) developed deep vein thrombosis/pulmonary embolism (DVT/PE) during admission, 7 people (17%) had acute kidney injury requiring dialysis, and 10 people ( 24%) had sepsis.
Their brain pathological examination showed that hypoxic/ischemic injury is very common, and almost all brains have it, with varying degrees.
Acute pathology includes neuronal contraction, eosinophilia, and reactive astrocytes; subacute pathology is manifested as infarction with macrophage infiltration, reactive astrocytes, and new blood vessels.
A small number of patients (9/22%) developed multiple lesions involving the cortex, hippocampus, cerebellum, and brain.
Vascular-related pathological manifestations are also common.
Acute, subacute, or chronic infarcts were found in 18 people (44%), and 10 people (24%) had multiple small infarcts.
The researchers also found that microglia activation is also very common.
Diffuse microglia activation was found in 34 people (81%), and there were glial cell nodules in 26 people (63%), including a small number of T cell aggregations.
.
It can be seen that the microglial cells are activated but there is very little inflammation around blood vessels and lymphocyte infiltration into the brain parenchyma.
This is in sharp contrast with the tissue analysis of one of the patients with HSV-1 infection.
It can be seen that compared with HSV1 infection (below), the new crown infection has less lymphocyte infiltration.
In addition, many patients have developed pathological changes of neurodegenerative diseases, but this is not surprising considering the overall age of the patients.
Since it was previously speculated that the new coronavirus may enter the brain through the olfactory nerve, the researchers specifically checked the pathological manifestations of hydrangea and found that only a very small number of T cells and mild to moderate microglia were activated.
It can be said that the pathological manifestations are very mild.
Proportion of main pathological findings Next, the researchers used qRT-PCR to detect viral RNA in the patient’s brain, and at the same time detected the nasal epithelium as a control.
Surprisingly, the results of qRT-PCR targeting the N gene in 4 brain regions of 25 people found that the level of viral RNA in the brain is actually very low.
Almost all nasal epithelial test results were highly positive, with a median virus copy number of 43840; while the proportion of positive samples in the central nervous system and the number of virus copies were lower, 7 people (28%) were negative in all brain regions, only 9 People (36%) have multiple positive brain areas.
At the same time, viral RNA was detected in the brain area, and there is no correlation between the pathological manifestations of the tissue, which means that the pathological changes in the brain are probably not caused by the direct infection of the new coronavirus.
qRT-PCR analysis results In order to determine whether the new coronavirus can enter the brain, the researchers used RNAscope to further search for the presence of viral RNA, but no matter whether it was for the N region or the S region or a combination of the two probes, nothing was detected.
The presence of viral RNA.
This means that the new coronavirus cannot enter the brain, or their content is extremely rare, below the detection limit of RNAscope.
The researchers believe that the small amount of RNA fragments previously detected by qRT-PCR may come from circulation.
The researchers also searched for the presence of the N protein of the new coronavirus in the brain through immunohistochemistry, but also did not find it.
RNAscope detects the comparison of brain and lung tissues.
There is only one case of the patient’s brain showing perivascular infection.
In general, these findings prove that the brain damage of the new crown patient does not come from the direct attack of the new crown virus.
The main pathological manifestations can actually be divided into two The first is the damage caused by hypoxia, and the second is the attack of activated microglia on neurons (neurophagocytic phenomenon).
The former is not uncommon in the course of new coronary disease.
New coronary pneumonia itself has severe lung damage, and hypoxia can be regarded as a common pathology.
At the same time, hypoxia can further induce neurons to express signals and be engulfed by microglia.
The microglia found by the researchers mainly exist in the brainstem and are involved in the regulation of heart rate, breathing rhythm, and consciousness.
The effect on the hippocampus may affect mood and memory.
This may explain the many mental and neurological symptoms of patients with new crowns.
References: [1] Kiran T Thakur, Emily Happy Miller, Michael D Glendinning, Osama Al-Dalahmah, Matei A Banu, Amelia K Boehme, Alexandra L Boubour, Samuel S Bruce, Alexander M Chong, Jan Claassen, Phyllis L Faust, Gunnar Hargus, Richard A Hickman, Sachin Jambawalikar, Alexander G Khandji, Carla Y Kim, Robyn S Klein, Angela Lignelli-Dipple, Chun-Chieh Lin, Yang Liu, Michael L Miller, Gul Moonis, Anna S Nordvig, Jonathan B Overdevest, Morgan L Prust, Serge Przedborski, William H Roth, Allison Soung, Kurenai Tanji, Andrew F Teich, Dritan Agalliu, Anne-Catrin Uhlemann, James E Goldman, Peter Canoll, COVID-19 neuropathology at Columbia University Irving Medical Center/New York Presbyterian Hospital, Brain, 2021;, awab148, https://doi.
org/10.
1093/brain/awab148[2] The author of this articleDai Siyu
