One of the mysteries of the pandemic COVID-19 is why it causes few or no symptoms in some people, while others, usually older, may succumb to it. This small percentage of patients develops a series of severe symptoms that can cause death. Among them is the formation of thrombi and damage to the wall of blood vessels, which can cause heart attacks, strokes or kidney failure, among other serious problems.
What has been learned about the disease indicates that these symptoms are not caused by the direct action of the virus, but by the excessive activation of a particular component of the immune system. This component is called the complement system.
This system is capable of killing many bacteria and rendering many viruses useless. It is made up of 25 proteins found in blood plasma and in the fluids that bathe cells and tissues. These proteins are organized into three branches of action, each specialized in activating in a different way against microorganisms.
Two of these branches need one or the other microorganism to be detected in order to activate and act against it. In one of the branches, detection is carried out by proteins produced by the liver and released into the blood by the liver. This branch acts to stop the infection in its early stages, as soon as the infectious microorganism is detected. If this is not achieved, days later antibodies against the microorganism will be formed which, when detected, will trigger the second branch. Thus, one of these branches is immediate, while the other first requires the generation of antibodies to be able to activate.
However, these two activation branches are not enough to keep infections at bay. Therefore, the third branch is continuously activated, whether infectious microorganisms have been detected or not. This third branch, better called the third pathway of activation of the complement system, has been called the alternative pathway, but, in reality, it is the main pathway of action of this defense system. The problem with it is that it puts into operation molecules that are not only deadly to microorganisms, but can also kill our own cells. The “poison” that this route is continuously generating needs, therefore, an “antidote”.
Microorganisms cannot manufacture this “antidote”, but it is continuously produced by our cells, which are thus always protected from the toxic action of the alternative complement pathway.
Researchers at John Hopkins University School of Medicine, in a series of experiments, discover that the S protein of the coronavirus SARS-CoV-2, which is key to allowing the virus to enter cells, needs to bind to a cell membrane molecule to which one of the antidote molecules against complement activation must also bind. In severe infections, this can block the binding of antidote molecules to cells, and cells are thus affected by the uncontrolled action of complement.
In addition, excessive activation of this system triggers, as we say, a generalized inflammatory reaction that affects blood circulation. This reaction can generate thrombi that, depending on where chance wants them to occur, may affect one organ or another to a greater or lesser extent. If the affected organ is vital, death may even occur.
The most interesting and useful aspect of this new knowledge is that there are already drugs capable of modulating the level of activation of the alternative pathway of complement. Some of these drugs have been effective in cells grown in the laboratory to prevent the activity of this pathway in the presence of the S protein of the virus. SARS– CoV-2.
Jia Yu, et al. (2020). Direct activation of the alternative complement pathway by SARS-CoV-2 spike proteins is blocked by factor D inhibition. Blood.
Jorge Laborda, October 27, 2020.
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