June 27, 2022

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Mild symptoms of COVID-19 may cause potential brain damage



 

Mild symptoms of COVID-19 may cause potential brain damage

Nature: The impact of COVID-19 infection on the brain even mild symptoms may cause potential brain damage!


The new coronavirus, SARS-CoV-2, was initially thought to be a respiratory virus, but as the number of cases worldwide increased, it was recognized that the virus not only caused respiratory symptoms, but also affected multiple other organ systems, with the nervous system bearing the brunt.

 

A study of hospitalized patients in the United Kingdom found that during the acute infection of the COVID-19, the most common neurological symptoms of patients included: loss of smell, stroke, delirium, brain inflammation, brain lesions, etc.

 

Not only that, but loss of taste and smell, inattention, headache, sensory disturbances, sleep disturbances, depression and even mental illness may also act as sequelae of COVID-19 months after acute infection, persisting in some convalescent patients, even if Young patients with mild illness are no exception.

 

However, the mechanism by which the new coronavirus damages the brain has not yet been understood. The current mainstream view is that the new coronavirus may affect the function of the nervous system through immune activation, neuroinflammation, and cerebrovascular damage.

 

Mild symptoms of COVID-19 may cause potential brain damage

 

The autopsy results of patients with COVID-19 pneumonia showed that there was obvious inflammation in the brains of the deceased with the activation and infiltration of immune cells.

 

The risk of stroke was significantly increased in patients with acute COVID-19 infection compared with influenza, and this association persisted even after adjustment for stroke risk factors, and similar organ thrombosis and infarction were found in patients with COVID-19 and stroke patients increase.

 

Recently, a research team from Tulane University in the United States used a non-human primate model infected with the new coronavirus to reproduce the autopsy results of human cases, showing in detail how the new coronavirus affects the nervous system.

What is even more surprising is that infected monkeys without obvious respiratory symptoms also have brain damage changes in their brains. The research was published in Nature communications on April 1, 2022.

 

Mild symptoms of COVID-19 may cause potential brain damage

 

The research experimental group included 8 adult monkeys, including 4 rhesus macaques (RM) and 4 African green monkeys (AGMs) , who were infected with the original new coronavirus through multi-channel mucosal inoculation or aerosol aerosolization. strain (2019-nCoV strain) .

 

In addition, two adult rhesus monkeys and two African green monkeys were inoculated with virus-free medium through mucous membranes through multiple routes as a control group.

 

Within a week, the monkeys in the experimental group were successfully infected with the new coronavirus. Except for the early death of AGM1 and AGM2, the other monkeys survived to the end of the experiment.

 

AGM1 fell into a coma on day 8 post-infection, had only a mild response to stimulation, developed dyspnea, hypothermia, and hypoxemia, and was euthanized after anesthesia. AGM2 showed similar manifestations on day 22 post-infection, and euthanasia was also performed.

 

After the experiment, the monkey specimens from the experimental group and the control group were collected for analysis and comparison. The results showed that compared with the experimental group infected with the new coronavirus, compared with the control group, the monkeys in the experimental group had obvious inflammatory responses and extensive microglia in the brain. , activation of astrocytes.

 

Mild symptoms of COVID-19 may cause potential brain damage

 

After infection, different degrees of nucleolysis and neuronal apoptosis occurred in the brain neurons of monkeys in the experimental group, especially in the cerebellum and brainstem.

 

Not only that, more and larger microhemorrhages appeared in the brains of the monkeys in the experimental group, accompanied by the formation of microthrombi, especially in the brains of the earliest dead AGM1, a large number of hemorrhages were found. Probably one of the reasons for its rapid death.

 

Mild symptoms of COVID-19 may cause potential brain damage

 

Cerebrovascular injury will cause insufficient blood supply and oxygen supply to the local brain tissue. During the infection, the blood saturation of the monkeys in the experimental group fluctuated between 89% and 99%, and most of the time it was lower than 95%.

It also means the existence of mild hypoxemia, which corresponds to the concentration of carbon dioxide in the blood of the monkeys in the experimental group exceeding the normal physiological range.

 

The brain is an organ with a very vigorous metabolism. It is highly dependent on the ATP generated by aerobic glycolysis for energy supply. Long-term or intermittent reduction in blood oxygen saturation will cause cerebral hypoxia, energy metabolism disorders, and affect nerve cell activity. , eventually leading to nerve cell death and brain damage.

 

The evidence of cerebral hypoxia after infection with the COVID-19 is that compared with the control group, the expression of hypoxia-inducible factor HIF-1a in multiple brain regions of the monkeys in the experimental group increased significantly, and the brain cells Purkinje neurons that are very sensitive to hypoxic conditions and The surrounding cells degenerate and go to apoptosis.

 

 

Finally, the researchers tried to find traces of the new coronavirus in the brains of infected monkeys. Similar to the results of human autopsy, they could only find very few new coronaviruses in the blood vessels, suggesting that the brain tissue lesions of the monkeys in the experimental group were unlikely to be directly caused by the new coronavirus. caused by intrusion into the brain.

 

Based on the above findings, researchers believe that cerebral hypoxia plays an important role in the process of COVID-19 infection to neurological symptoms. This cerebral hypoxia may be caused by systemic hypoxemia combined with cerebrovascular damage. It can be very mild, but as long as it takes a long time, it will cause nerve cell damage and death.

 

More importantly, cerebral hypoxia did not only appear in those severe cases of dyspnea, but also in those infected with no obvious respiratory symptoms. A ubiquitous feature.

 

As with all ages, with or without complications, people with post-infection disease severity are at risk of developing COVID-19 neurological symptoms.

 

“Because the infected people did not show obvious respiratory symptoms, no one expected that these infected people might have potential brain damage,” said researcher Tracy Fischer.

 

She hopes that this study and more future research on the new coronavirus and the brain can point the way to treating and improving the neurological symptoms of the COVID-19 during the acute phase and the long-term COVID-19.

 

 

 

 

 

 

 

references

1. Rutkai, I., Mayer, MG, Hellmers, LM et al. Neuropathology and virus in brain of SARS-CoV-2 infected non-human primates. Nat Commun 13, 1745 (2022). https://doi.org /10.1038/s41467-022-29440-z
2. Spudich S, Nath A. Nervous system consequences of COVID-19. Science. 2022;375(6578):267-269. doi:10.1126/science.abm2052
3. Matschke J, Lütgehetmann M, Hagel C, et al. Neuropathology of patients with COVID-19 in Germany: a post-mortem case series. Lancet Neurol. 2020;19(11):919-929. doi:10.1016/S1474 -4422(20)30308-2
4. Merkler AE, Parikh NS, Mir S, et al. Risk of Ischemic Stroke in Patients With Coronavirus Disease 2019 (COVID-19) vs Patients With Influenza. JAMA Neurol. 2020;77(11):1366–1372. doi: 10.1001/jamaneurol.2020.2730

Mild symptoms of COVID-19 may cause potential brain damage

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