New clinical data confirms BG scientists’ hypothesis of COVID-19 complications

Studies by scientists at the Institute of Biology and Immunology of Reproduction (IBIR) at the Bulgarian Academy of Sciences (BAS) suggest that the overreaction of a complex protein complex called the NLRP3 inflammasome is at the root of the severe complications of COVID-19, BAS reported on April 29.

The inflammasome is a molecular sensor in cells that responds to a meeting with a pathogen and/or cellular damage, resulting in the release of inflammatory signals and a particular type of cell death - pyroptosis.

In doing so, the cells burst and release a huge amount of inflammation and danger signals to which neighbouring tissue cells and cells of the immune system respond. Normally, dead cells are eaten by cells of the immune system, such as macrophages, but in this case, the signals travel much further.

The inflammasome is part of the mechanisms of the innate immune response and for many years was thought to be present only in immune cells.

It has recently become apparent that such a complex is present in other cells, such as those in the respiratory tract, as well as the cells that build the blood vessels.

Prof. Dr. Soren Hayrabedyan and Prof. Krasimira Todorova of IBIR-BAS show for the first time in 2016 the possibility that this inflammasome can be activated even in epithelial cells, which create an immunological tolerant environment, leading to signals for inflammation and cellular death.

Two years later, this data was also confirmed in patients from a team led by Ludwig Maximilian University at Max Planck.

The first evidence of severe respiratory failure resulting from the so-called cytokine storm and sepsis led us to believe that this complex molecular complex may be related to this, since blocking the inflammasome in experimental models of sepsis stops the process, the scientists say.

At higher viral loads or in hereditary predisposition to a stronger than normal response, the inflammasome in the epithelial cells of the lung as well as in the cells of the small vessels may be activated.

It is strange that in lung cells this can lead to the release of inflammatory signals, but at the same time it strengthens the contact between them. However, with adjacent micro vessels, the effect can be dramatic - significant cell death, with a burst, which can cause gas or blood flow abnormalities.

All-new scientific articles from April 20-23, 2020 confirm this in patients with COVID-19, showing severe blood clotting phenomena in small vessels.

Inflammasomes are associated with various diseases in which the immune system is involved, incl. diabetes, multiple sclerosis, chronic ulcerative colitis, rheumatoid arthritis, gout and sepsis. Models of sepsis are interrupted by blocking the inflammasome with an inhibitor.

Chloroquine, which has been investigated as a potential agent against COVID-19 and given in patients with rheumatoid arthritis and lupus, is a direct blocker of the same inflammasome and may suppress a sepsis pattern. Most often, its mechanisms of action, established in the 80-90 years of the last century, are cited, since inflammasomes were only discovered recently.

The hypothesis of the two IBIR scientists could explain both the cases in young people - the over-activation of inflammasomes and the more severe course in people with high blood pressure, diabetes, atherosclerosis, since in the latter, it is precisely the cells of the small vessels are affected.

It is important to note that inflammasomes are involved in the pathogenesis of diabetes and atherosclerosis and are already active. The blockage of inflammasomes leads to the stoppage of vessel inflammation patterns in Kawasaki disease, with coronary vessels inflammation and fever.