When we hear or read about the status of severe COVID-19 patients, one of the terms we have heard the most about is ‘cytokine storm’. But what are cytokines? Why this chemical surge can kill critical patients infected by the SARS-CoV-2 coronavirus? During an interview conducted for Muy Interesante, Dr. Francisco José Roig Vázquez, pulmonologist at the 12 de Octubre hospital in Madrid, illustrated us about this process, which he qualifies as the most frequent cause of death in critical cases of COVID-19, and offers us clues on how to control it.
First of all, let’s put ourselves in the situation. When the coronavirus enters the respiratory tract, the first thing it does is come into contact with epithelial cells and with cells called type 2 pneumocytes. So that this virus can invade cells, it injects its RNA into them, and then this genetic material multiplies, as much as that from a single cell some 10,000 copies can come out.
For this process, the coronavirus uses several ‘allies’, which are the ACE2 receptor and the CD147 receptor, present in our body. This coronavirus ‘tricks’ the immune system, because, in order to enter the cell, it blocks both receptors and leaves them permanently open; “It is like a key that breaks several locks and leaves the doors open,” explains Roig. With these receptors blocked, the virus penetrates more easily, and the more receptors there are and open at the same time, the more infection there will be in the body.
When the coronavirus infects our cells, the innate immune system kicks in. As if we were inside the classic animation Once upon a time in the human body , we must imagine how various types of cells come into action to defend the organism, among them, macrophages, leukocytes, interferon, NK lymphocytes (called killer cells). The most important are macrophages, which target the coronavirus RNA to kill it, and they devise the action of proteins called cytokines, responsible for fighting the invading genome.
“At this moment two things can happen: the first is that, thanks to the release of these cytokines and the blocking action of interferon, our body can defeat the virus; hence there are patients with coronavirus with hardly any complications and who have not needed any type of medication, “explains the doctor. “But there are around 5 or 10% of patients, we still don’t know why, whose cytokine response is magnified. The discharge of cytokines is very intense, and our immune system, which is the main tool we have to defend ourselves, then becomes our worst enemy ”, he continues.
We therefore understand that the controlled release of cytokines is not only not harmful, but is necessary to fight infection; only when this reaction gets out of control, and can pose a threat to the body itself , are we talking about a ‘cytokine storm’.
During a cytokine storm, a kind of autoimmune reaction is created, a fight against our own body, which causes inflammation in several organs: at the level of the lung, liver, kidneys … Specifically in the lung, this cytokine storm causes an edema, a buildup of fluid, which makes breathing ability much more difficult with respiratory failure. This is the main cause of death for COVID-19 patients: “Most COVID-19 patients who die are because they have reached this situation,” concludes Dr. Roig. “In addition, the interior of the blood vessels becomes inflamed and thrombi are produced, which further aggravate the situation,” he adds.
How to stop the cytokine storm?
If the normalized release of cytokines is a common process in the body every time we have an infection, is there a way to stop it in those patients in whom it is uncontrolled? According to Dr. Roig: “In most patients nothing bad happens, but in those who unleash an uncontrolled cytokine storm, we can only do something in about half.” The reason, he explains, is that many of them have a weakened, aged immune system or other adjacent diseases that complicate everything more. “Whether the patient lives or dies will depend on our being able to control this cytokine storm,” he concludes.
In these cases, treatment is aimed at using respirators, corticosteroids, and heparin to avoid thrombi. But, in addition, there are now monoclonal antibodies capable of blocking this cytokine discharge, which are being tested in clinical trials.
