COVID-19 is generally known as a type of respiratory disease, but there is growing evidence suggesting that the infection can severely affect other organs, including the brain. Ádám Dénes and his colleagues were among the first researchers in the world to examine the brains of people whose death is related to the coronavirus infection. Their results might lead to the development of treatment methods that are different from previous ones.
Severe pneumonia, artificial respiration, chronic illness, high rate of mortality among elderly people − these are the major keywords appearing in the news every day in connection with the outcome of coronavirus-related diseases. The virus was named SARS-CoV-2, and the first half of the acronym comes from the abbreviation of the severe acute respiratory syndrome. As the name suggests, the primary symptoms affect the respiratory tract and the lungs.
However, as more and more clinical data is available on the disease, growing evidence suggests that both the nervous system and the brain may be involved in the infection, and research in this area might be crucial in the most severe cases. Ádám Dénes, a researcher at the Institute of Experimental Medicine (abbreviated KOKI in Hungarian), and his colleagues, including neuropathologist Tibor Hortobágyi, wanted to map the possible neurological effects of the current coronavirus infection, MTA reported.
When we have an infection, our immune system reacts specifically to pathogens and foreign substances, such as the cell wall of bacteria and the genetic material or the protein shell (capsid) of viruses. The entry of these pathogens causes inflammatory reactions in the human body. In response to this reaction, our liver starts to produce acute-phase reactants that prepare our body for defence. By switching to “emergency mode,” the body is forced to retune many of its systems that function properly in a normal situation. Similar processes occur in the case of other diseases; for example, certain chronic diseases, such as high blood pressure (hypertension) or diabetes, already keep the body’s inflammatory system under constant stress.
Inflammatory changes in the body are also perceived by our nervous system, and through the reaction of some of our brain centres, especially the hypothalamus, the well-known symptoms of malaise, loss of appetite, fever, and other common symptoms start to develop. However, the impact of viral infections can go even further.
The overproduction of inflammatory factors can also trigger processes that can affect brain centre circulation and the respiratory centre. This phenomenon might stand behind the clinical observations in which the respiration of some COVID-19-infected patients collapsed in a way that would not otherwise be justified by the condition of their lungs.
Similar processes caused by systemic inflammation − including circulatory collapse, cardiac arrest, liver, kidney, or other organ dysfunction, and various neurological symptoms − can be observed in septic conditions caused by bacteria or viruses.
However, there is an even more alarming way to explain such symptoms: the virus enters the brain.
“Previous, non-pandemic, but dangerous coronaviruses, such as SARS (Severe Acute Respiratory Syndrome, identified in 2003) and MERS (Middle East Respiratory Syndrome), were shown to be able to cause nervous system infections. A number of symptoms can be identified, such as loss of taste and smell, headache, confusion, sudden fever or stroke, seizures, and spasms, which suggests that the novel coronavirus has this ability,” Ádám Dénes explained.
The loss of smell can also indicate that the virus can reach the olfactory bulb located in the brain along the nerve pathways. However, it can also reach the medulla oblongata, the respiratory centre, the hypothalamus, or areas of the brain next to the ventricles through the peripheral nerves or the walls of cerebral vessels.
The possibility of brain infection is also increased by the fact that the angiotensin-convertase enzyme-2 (ACE2), serving as the main entry point into cells for some coronaviruses, is attached to the cell membranes of cells in the lungs, arteries, heart, kidney, and the nervous system. Additionally, it is not unusual for viruses to be able to spread through the synapses (junctions) of nerve cells.
The involvement of the nervous system is further confirmed by the latest research of the Hungarian network scientist, Albert-László Barabási. In the Network Medicine Framework for Identifying Drug Repurposing Opportunities for COVID-19, he adapts a network-based toolset to COVID-19 to analyse the relationship of viral and human proteins. (“SARS-CoV2 infects human cells by hijacking the host’s translation mechanisms to generate 29 viral proteins, which bind to multiple human proteins to initiate the molecular processes required for viral replication and additional host infection,” said Barabási.)
Ádám Dénes, his colleagues (researchers at the Institute of Experimental Medicine), and Tibor Hortobágyi, a neuropathologist, were among the first researchers in the world to start the preparations and the licensing process facilitating the examination of nervous tissue samples of patients who died of COVID-19. Their goal is to find out whether the virus can infect the nervous system and, if so, which areas of the brain may be affected.
If the mechanisms of the cerebral effects of the virus can be revealed, some antiviral drugs could improve the chances of patients by reducing cerebral viral infection.
This research could also provide a chance to inhibit the inflammatory processes in the brain caused by the novel coronavirus, possibly with drugs that are already on the market to ensure safety. In addition, the study of the long-term effects of infection and associated inflammatory processes on the nervous system could play an important role in rehabilitation and the understanding of patients’ mental status.