What is a cytokine storm and does the coronavirus really cause it?

What is a cytokine storm

The term "cytokine storm" (hypercytokinemia) refers to Hypercytokinemia, an overly powerful reaction of the immune system in response to any stimulus - most often an inflammatory process.

In this state, too many cytokines Cytokines, Inflammation and Pain - NCBI - NIH are released into the blood. These tiny proteins are part of Is a “Cytokine Storm” Relevant to COVID-19? so-called innate immunity and play an important role in protecting the body from all kinds of infections - viral, bacterial, fungal.

Cytokines include:

Interferons. These proteins are popular immunomodulators that are often used to prevent colds. Although the effectiveness of these substances against ARVI has not yet been proven Treatment with interferon. But, for example, their ability to improve the condition of patients with chronic hepatitis B, scientists call "encouraging."
Lymphokines are the so-called cytokines that are produced by lymphocyte cells.
Monokins. Their "authors" are monocyte cells.
Interleukins. These are cytokines produced by white blood cells and serve to interact with other white blood cells.
Dozens of other types.

Some cytokines enhance a pre-existing inflammatory response to kill a pathogenic virus or bacterium. Others monitor this reaction and prevent it from becoming too powerful. Still others affect the production of hormones to protect the body in extreme conditions of illness. Others take control of the nervous system, for example by starting or stopping pain.

The interaction of cytokines with each other, as well as with other cells, organs, tissues, is an incredibly complex process and is still poorly understood. One thing is clear: without cytokines, our body could not cope with even the slightest scratch, not to mention more serious injuries and diseases.

But sometimes the immune system fails and too many cytokines are released. The problem is that this reaction is often a cascade: the formed cytokine provokes cells to produce more and more of its "congeners", the amount of pro-inflammatory (causing inflammation) cytokines grows, regulatory proteins do not have time to suppress their activity. Powerful inflammation engulfs various organs and tissues, and the situation becomes unmanageable. This is how a cytokine storm occurs.

Why is a cytokine storm dangerous?

Inflammation interferes with the functioning of the organ that it affects. For example, damage to the lungs prevents the body from breathing normally. And the inflammatory process in the heart and blood vessels leads to insufficient blood supply, increases the risk of severe internal bleeding or thrombosis (which means stroke and heart attack as well).

A cytokine storm causes large-scale inflammation of many organs at once. And as a result, it often leads to multiple organ failure - when neither the lungs, nor the heart, nor the liver, nor the kidneys can perform their functions normally, and all this happens at the same time. Failure of internal organs is highly likely to result in death.

A paradoxical situation arises: in a cytokine storm, the immune response to a disease is more dangerous than Cytokine Storm than the initial infection.

In fact, the body destroys itself.

What are the causes of the cytokine storm

Science is still at a loss for Cytokine Storm to answer this question. There is an assumption that the matter is in the so-called defect in the immune response. In some people, the body is inherently genetically predisposed to overreact to certain stimuli.

The key word here is some. So, if we talk about pathogenic viruses and bacteria, not all of them provoke a cytokine storm. A person can get sick with ARVI and bacterial infections dozens of times, recover easily and quickly. But when it encounters a specific virus, the body will give out hypercytokinemia.

An example of such a virus is the 1918-1919 pandemic influenza. It is assumed that the famous Spanish woman was so lethal precisely because it massively caused a failure of immunity and a cytokine storm in its victims.

Other causes of hypercytokinemia can be:

Certain therapies that increase the activity of the immune system. For example, CAR T cell therapy, which is used to fight cancer.
Autoimmune diseases - systemic lupus erythematosus, rheumatoid arthritis.
Taking some medications.
Sepsis is an extensive infection of organs and tissues with any pathogen. Inflammation, even large-scale, with sepsis is the norm - in this way the body fights the infection. But sometimes infection can be accompanied by a cytokine storm, that is, a sharp uncontrolled increase in the level of cytokines.

Does coronavirus cause a cytokine storm?

This may be surprising, because cytokine storms are often talked about in conjunction with the severe course of COVID-19, but it seems that there is no Cytokine elevation in severe and critical COVID-19: a rapid systematic review, meta-analysis, and comparison with other inflammatory syndromes. Recent studies show that blood levels of cytokines are not so high during coronavirus infection. Is a “Cytokine Storm” Relevant to COVID-19? so that we can talk about hypercytokinemia.

Rather, the powerful, destructive inflammation that some COVID-19 victims are experiencing is sepsis. The coronavirus infects organs and tissues more actively than previously thought, and with the help of the resulting inflammation, the body is trying to destroy the pathogen.

What are the symptoms of a cytokine storm

The signs of Cytokine Storm cytokine storm in almost all patients are the same and do not depend on what exactly caused the immune overreaction.

Fever. Temperatures often exceed 39 ° C and are not knocked out by standard means.
Respiratory symptoms - cough, shortness of breath, breathing problems. They can worsen to acute respiratory distress syndrome (ARDS), which requires oxygen therapy. And in severe cases - artificial lung ventilation (ALV).
Weakness, dizziness, headaches.
Clouding of consciousness up to its loss, neurological disorders.
Pain in muscles and joints.
Diarrhea.
Rash.

However, you should not rely on symptoms in this case. The fact is that even doctors find it extremely difficult to understand what exactly caused the deterioration of the patient's condition. The same signs can indicate both a cytokine storm and the effect of the underlying disease. A good example is COVID-19: as we said above, scientists today assume that severe manifestations of the disease are associated with sepsis, and not with hypercytokinemia.

There are few symptoms to diagnose cytokine storm. More research is needed: blood tests for cytokine levels and markers of the acute phase of inflammation (for example, C-reactive protein and ferritin), laboratory assessment of kidney and liver function, and other tests.

This examination is so difficult that it can only be carried out in a hospital setting. Most often, given the severity of the symptoms, this occurs in intensive care.

How to treat a cytokine storm

Only in intensive care! A person with a cytokine storm needs constant supportive therapy, including oxygen, and health monitoring, A look within cytokine storms.

Hypercytokinemia itself, as a rule, is tried to be stopped with the help of immunosuppressive drugs. These include, for example, drugs based on tocilizumab and hydroxychloroquine. They reduce the activity of inflammatory cytokines. But we will repeat again: it makes sense to use such means only if the diagnosis “cytokine storm” is unambiguously made.

Because COVID-19 may not be associated with a cytokine storm, drugs to suppress immunity are sometimes not helpful in coronavirus.

However, even if the diagnosis is correct, and the treatment was started on time, it is not always possible to defeat the cytokine storm. We, humanity, still know too little about how our body works. Therefore, we find ourselves powerless even before the smallest protein molecules - cytokines.