People with severe COVID-19 seem to have an imbalance in a key immune system signaling pathway.
This may be why they have such a severe form of the disease.
The article, “Severe COVID-19 is associated with an imbalance in an important immune system signaling pathway,” by Anna Julia Pietrobon and Maria Notomi Sato, published in Frontiers in Immunology, found that severe COVID-19 is associated with an imbalance in the signaling system and a dysfunction in the regulation of these components, which in turn leads to a pro-inflammatory state and a potentially fatal systemic inflammation known as a cytokine storm. The researchers found that cell-surface ectonucleotidases that cleave ATP to be less expressed in cells from both mild and severe COVID-19 patients, but particularly the latter. In fact, they concluded that the higher the ATP level, the more severe the disease. The researchers also investigated possible alterations in immune system cells. They found that some immune cells, especially B lymphocytes, expressed less CD39 and CD73, enzymes that break down ATP. Lymphocyte levels generally tend to be low in COVID-19 patients, but in their study not only the levels of B cells in blood from severe patients were low, but these cells also expressed lower amounts of both enzymes, contributing to less ATP metabolization and hence less production of adenosine, the anti-inflammatory component that would try to regulate this response. Given this finding, the researchers decided to isolate the B cells present in the blood samples and provide them with ATP. However, they found that the build-up of ATP in conjunction with low
Researchers at the University of São Paulo (USP) in Brazil have found that severe COVID-19 is associated with an imbalance in an important immune system signaling pathway.
The discovery helps explain at the molecular level why some people infected by SARS-CoV-2 develop a potentially fatal systemic inflammation.
The study, published in Frontiers in Immunology, found that severe COVID-19 is associated with an imbalance in the signaling system and a dysfunction in the regulation of these components, which in turn leads to a pro-inflammatory state and a potentially fatal systemic inflammation known as a cytokine storm. The researchers found that cell-surface ectonucleotidases that cleave ATP to be less expressed in cells from both mild and severe COVID-19 patients, but particularly the latter. In fact, they concluded that the higher the ATP level, the more severe the disease.
The researchers also investigated possible alterations in immune system cells. They found that some immune cells, especially B lymphocytes, expressed less CD39 and CD73, enzymes that break down ATP. Lymphocyte levels generally tend to be low in COVID-19 patients, but in their study not only the levels of B cells in blood from severe patients were low, but these cells also expressed lower amounts of both enzymes, contributing to less ATP metabolization and hence less production of adenosine, the anti-inflammatory component that would try to regulate this response. Given this finding, the researchers decided to isolate the B cells present in the blood samples and provide them with ATP. However, they found that the build-up of ATP in conjunction with low
The increase in unmetabolized ATP, according to the article, produces a pro-inflammatory state and triggers a potentially fatal systemic inflammation known as a cytokine storm.
Severe COVID-19 patients had higher levels of ATP in their blood and lower levels of adenosine.
As the researchers explain, ATP is a molecule that provides energy to cells. It is constantly being produced and broken down in the body. However, in order for ATP to be broken down, it needs to be converted into adenosine by enzymes called ectonucleotidases.
In people with severe COVID-19, there is an imbalance in this process. The cell-surface ectonucleotidases that cleave ATP to produce adenosine are less expressed in cells from both mild and severe COVID-19 patients, but particularly the latter. This means that there is a build-up of unmetabolized ATP in the body.
ATP is not only a source of energy for cells, but it also has other functions. For example, it plays a role in immune system signaling. When ATP accumulates outside of cells, it can bind to receptors on immune cells and trigger a pro-inflammatory response. In fact, the researchers found that the higher the ATP level, the more severe the disease.
This pro-inflammatory response can lead to a potentially fatal systemic inflammation known as a cytokine storm. Cytokine storms are characterized by an overproduction of inflammatory cytokines and can cause organ damage and failure. They are often seen in people with severe infections or autoimmune diseases.
The researchers also investigated possible alterations in immune system cells. They found that some immune cells, especially B lymphocytes, expressed less CD39 and CD73, enzymes that break down ATP. Lymphocyte levels generally tend to be low in COVID-19 patients, but in their study not only were the levels of B cells in blood from severe patients low, but these cells also expressed lower amounts of both enzymes, contributing to less ATP metabolization and hence less production of adenosine.
Given this finding, the researchers decided to isolate the B cells present in the blood samples and provide them with ATP. They found that when they did this, the B cells from patients produced less adenosine than those from healthy controls indicating that there was indeed an imbalance in ATP metabolism in these patients.
It should be noted that the researchers do not yet know if the alteration in ATP metabolization causes or is caused by the exacerbated inflammatory response to SARS-CoV-2. However, this is an important discovery that helps explain at the molecular level why some people infected by the virus develop a potentially fatal systemic inflammation. The researchers plan to investigate this in future projects.
In the study, the researchers measured ATP and adenosine levels in blood samples from 88 severe COVID-19 patients collected in 2020-21.
None of the patients had been vaccinated.
Given this finding, the researchers decided to isolate the B cells present in the blood samples and provide them with ATP.
The B cells from patients produced less adenosine than those from the healthy controls.
It should be noted that the researchers do not yet know if the alteration in ATP metabolization causes or is caused by the exacerbated inflammatory response to SARS-CoV-2.
They plan to investigate this in future projects.