- What effects can a corona infection have on the brain?
- Researchers in the USA have investigated this question.
- Here we explain why their study is important and what the result could also mean for the treatment and prevention of Long COVID.
US researchers from the National Institute of Neurological Disorders and Stroke use autopsy material from corona dead to show the consequences of an infection SARS-CoV-2 can have on the nerve tissue. After that, less of that seems Virus itself, but rather a misguided immune response to be responsible for the death of nerve cells and the formation of tiny blood clots in the microvessels of the brain.
Why the study is important
Soon after the start of the pandemic, it became clear: COVID-19 is not just a respiratory disease. In addition to the lungs, other organs can also be damaged by the corona infection – such as the heart, blood vessels, kidneys, brain, liver. The virus itself can destroy tissues as it multiplies in cells. But the immune system is also involved in the damage when it attacks virus-infected cells.
Some patients with a corona infection develop neurological complications. This can happen during the acute phase of the disease or later. Many complain of difficulty concentrating, sleep disorders, headaches, Fatigue, sensory problems or even get a stroke close to the corona infection. COVID-19 may be able to do that risk of Alzheimer’s dementia increase or accelerate the course of the disease.
It is not yet clear how the virus damages nerve cells and what exactly triggers the neurological symptoms. In order to develop strategies for therapy or prevention, it is absolutely necessary to better understand the disease processes.
What the researchers did
Avindra Nath is a neuroimmunologist who has studied the neurological consequences of viral infections, particularly HIV/AIDS and influenza, for decades. Nath and his team from the National Institute of Neurological Disorders and Stroke in Bethesda, USA, published their first one a year and a half ago Observations on patientswho died of COVID-19 during the first corona wave. The researchers had examined the brain of the deceased with the MRI. In some of them, they discovered conspicuous tissue injuries scattered over the examined brain areas.
In the current investigation, the Americans tried to find out how the damage could have happened. To do this, they prepared tissue sections from different regions of the brain. Using special staining and other detection methods, they examined the tissue for the presence of immune cells, signaling substances, tiny blood clots and SARS-CoV-2.
The autopsy material came from two women and seven men, ages 24 to 73, who died from COVID-19 from March to July 2020. Five of them died very suddenly, only one had been treated in intensive care because of a severe course of the disease.
What the results of the study look like
Although the deceased carried the virus at the time of their death, SARS-CoV-2 was not detected in any of the brain samples examined. However, Avindra Nath’s team found clear signs of destruction of the protective blood-brain barrier in the damaged areas of the brain in all of the deceased. The protein fibrinogen, normally found in blood serum, had leaked into brain tissue.
The wall cells that line the microvessels of the brain were activated, immune complexes of antibodies and components of the “complement cascade” (a defense system that supports the elimination of pathogens) had accumulated, inflammatory cells had migrated, some of the tiny vessels were blocked by blood clots. Nerve cells had died off in the vicinity of these foci of inflammation. The US team discovered most lesions in the so-called hindbrain, which also includes the cerebellum and brainstem.
The researchers suspect that antibodies against the virus or autoimmune antibodies triggered the immune cascade and caused the damage.
What weaknesses does the study have?
Despite various technical efforts, the researchers were unable to detect the coronavirus in brain tissue. This does not necessarily mean that the virus was not present in the brain at a specific point in time, which the study does not record. The negative result may have been caused by extremely small amounts of virus below the detection limit or methodological errors. Because most of those affected were found dead, there was insufficient data on the medical history or the course of the COVID-19 disease.
The probability that the virus and the triggered immune reaction are responsible for the damage is extremely high. Nevertheless, it cannot be completely ruled out that the injury to the blood-brain barrier (with clot formation and inflammation) is not also due to other events outside of the corona infection, Avindra Nath and his colleagues restrict their results.
What the result means
Actually, because of the damage to the brain tissue, he expected to detect the corona virus on the spot, says Avindra Nath. Some other previous studies had also found no or extremely little virus material in the central nervous system. According to the neuroimmunologist, these virus quantities, if they were only small at all, were by no means sufficient to explain the observed effects on the brain and the neurological consequences opposite the magazine “Science”.
It may have been the immune reaction to the infection that (partly) caused the death of those affected. Had the patients survived, the processes triggered might have led to long COVID, Avindra Nath speculates. It is possible that this immune reaction continues to some extent in long-COVID patients and causes the nerve damage and neurological symptoms, says Nath. Therapies that mitigate these adverse events could potentially help those affected. One must prevent immune complexes from being deposited in the blood vessels, which led to the turbulence.
In fact, in the US, under the aegis of Avindra Nath, it begins in these weeks a studywhich tests whether drugs that inhibit the immune response Long-COVID-affected can be helped. The researchers are testing the drug methylprednisolone, which inhibits inflammation, as well as high-dose immunoglobulin preparations that, among other things in certain autoimmune diseases come into use.
It is not yet known exactly why they can mitigate the attack on the body’s own tissue, for example in multiple sclerosis. Presumably, the highly concentrated antibody preparations inhibit the production of auto-antibodies and reduce the release of inflammatory substances.
About which the investigation makes no statements
It is still unknown which antigen triggers the misguided immune reaction. Also, why some people get neurological complications and others don’t. Immune complexes of antibodies and the spike protein of the virus may have formed. These accumulated at the ACE-2 receptor on the vessel wall and thereby triggered the inflammatory processes.
Or in the course of the immune reaction, auto-aggressive antibodies have formed that do not bind to the spike protein of the coronavirus, but to its “opposite”, the ACE2 protein on the vascular wall cells. Whether similar mechanisms actually form the basis of Long COVID can only be speculated on the basis of these study results.
Sources used:
- Oxford University Press: Neurovascular injury with complement activation and inflammation in COVID-19
- Alzheimer’s Association: Alzheimer’s-like signaling in brains of COVID-19 patients
- National Library of Medicine: Microvascular Injury in the Brains of Patients with COVID-19
- Science.org: Here’s what we know about COVID-19’s impact on the brain
- ClinicalTrials.gov: Immunotherapy for Neurological Post-Acute Sequelae of SARS-CoV-2
- Medical journal: Autoimmune diseases: Broader use of immunoglobulins