The new crown causes nerve problems! Academician Bian Xiuwu and other teams have revealed the underlying mechanism of neurological symptoms caused by the new coronavirus

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Written by Sophia

Severe neurological symptoms are associated
with coronavirus disease 2019 (COVID-19).
However, despite evidence of neurotropic infection, its morphological features, pathological properties, and underlying mechanisms in the patient's brain have not been revealed
.

On January 6, 2023, Bian Xiuwu of University of Science and Technology of China/Army Medical University, Leng Ling of Chinese Academy of Medical Sciences/Peking Union Medical College Hospital, and Yifang Ping and Yao Xiaohong of Army Medical University published the title "COVID-19-associated monocytic encephalitis (CAME): histological" in the journal Signal Transduction and Targeted Therapy and Proteomic Evidence from Autopsy", collaboration reveals the underlying mechanism by which the novel coronavirus causes neurological symptoms
.

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Research background

 01 

COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), defined as a systemic infectious disease
that causes multiple organ dysfunction syndrome.
The global pandemic of the disease has killed more than 6.
6 million people, especially among
older adults with lung and cardiovascular disease.
Although most people with COVID-19 present primarily with respiratory symptoms, there is growing recognition that people with COVID-19 have a wide range of neurological symptoms, manifestations, and complications
.
Major neurologic manifestations, from mild to severe, include anxiety, depression, visual changes, immobility, numbness of the extremities, tremor, and myalgia, and loss
of memory, hearing, taste, or smell.
Acute mild or severe COVID-19 (called "long COVID") may be followed by a persistent range of symptoms that can affect multiple organs
, including the central nervous system.
Understanding the pathological nature and mechanisms of neurological manifestations is important
to improve COVID-19 outcomes.

Study results

 02

To study neuroinflammatory pathways in COVID-19-associated monocytic encephalitis, the researchers compared proteomic features
between COVID-19 and control brains.
A total of 4587 proteins were identified in the brain tissue of COVID-19 patients and 4414 proteins
in control brain tissue.
4351 proteins (93.
6%)
were detected in COVID-19 and control brains.
Using principal component analysis (PCA) to quantify protein differences identified in COVID-19 and control brains, it was revealed that there were significant differences between the two groups, i.
e.
, a total of 572 proteins were expressed
differently in COVID-19 brains compared to control brains.
Proteomic results showed that microglia and astrocytes in the brains of COVID-19 patients were activated, releasing inflammatory mediators (IL-4, -6, -12, etc.
), leading to brain damage
.

f Proteomics Research Protocol
.
gPrincipal component analysis
of 15 samples based on quantitative profiles of brain tissue proteins.

To better understand inflammatory exudation in the brain of COVID-19, we studied pathological changes
in the blood-brain barrier (BBB).
Studies have found that swollen endothelial cells and discontinuous perivascular astrocytes have been found to be accompanied by edema.

Electron microscopy confirms BBB injury with capillary endothelial cell swelling, abnormal tight junctions, basal rupture, and glial membrane swelling
.
Quantitative analysis of cerebral vascular cerebral edema showed that the widening of the perivascular space of the brainstem was most severe
in each brain region.
In addition, the degree of cerebral oedema was significantly associated with BBB damage and astrocytes activation, and cerebral endothelial cells were occasionally positive
for SARS-CoV-2 protein.
These results indicate impaired BBB integrity in the brain with COVID-19 and viral infections
in the vasculature.

Structural damage and molecular alterations of the blood-brain barrier (BBB) in the brain of COVID-19

Research significance

 03 

The study identified the molecular signature
of COVID-19-associated encephalitis with monocytes infiltration and glial cell activation through systematic pathological and proteomic analysis of the COVID-19 autopsy brain.
Monocytes infiltration and microglia activation suggest that they have the potential to be therapeutic targets for COVID-19
.

This study was conducted on the brains of deceased COVID-19 patients infected with SARS-CoV-2 in Wuhan, China, in 2020, with certain limitations, including a lack of experiments from animal models, in vitro organoid infections, and protein function to confirm the conclusions
.
In addition, further investigation should include comparing changes in brain pathology and protein profile with patients with COVID-19 with Omicron infection
.

In summary, the results of this study identify the histopathological and molecular characteristics of COVID-19-associated monocytic encephalitis and suggest potential therapeutic targets
.

Resources:

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Note: This article is intended to introduce the progress of medical research and cannot be used as a reference
for treatment options.
If you need health guidance, please go to a regular hospital
.