COVID-19 Cytokine Storms
COVID-19 Cytokine Storms

COVID-19 comes with a host of symptoms. They can vary dramatically from patient to patient depending on age, preexisting health factors, and in some cases, for no discernible reason at all. However, in severe and critical cases, the majority of patients experience what is called a "cytokine storm".

What Is a Cytokine Storm?

"Cytokine storm" has no firm definition. Instead, it’s a general term applied to a situation in which the body’s immune system improperly releases unregulated cytokines in response to a threat. This condition also goes by several other names, including cytokine release syndrome, hemophagocytic lymphohistiocytosis, and macrophage activation syndrome.

Cytokines are so-called killer cells designed to stop an invader and destroy it. However, it doesn’t always work that way. According to the University of Alabama at Birmingham,

"Killer cells are often defective, resulting in increased production of inflammatory proteins that can lead to organ failure and death."

The National Cancer Institute offers the following definition:

"A severe immune reaction in which the body releases too many cytokines into the blood too quickly. Cytokines play an important role in normal immune responses, but having a large amount of them in the body all at once can be harmful."

What Causes a Cytokine Storm?

Ultimately, the underlying cause of a cytokine storm is an infection or other stimuli. However, the problem is the body’s overproduction of cytokines and their unregulated release in an attempt to stop the invader. In short, too many immune cells are activated within a single place in the body, which causes serious problems and can lead to dangerous, even deadly complications. In some cases, a cytokine storm can lead to sepsis, multi-organ failure, and death.

The National Cancer Institute weighs in by explaining,

"A cytokine storm can occur as a result of an infection, autoimmune condition, or other disease. It may also occur after treatment with some types of immunotherapy."

The exact trigger of cytokine storms remains elusive, though.

What Are the Symptoms of a Cytokine Storm?

Cytokine storm symptoms vary from patient to patient. However, there are some commonalities seen across the board. Some of the most widespread symptoms include the following:

  • High fever
  • Inflammation
  • Extreme fatigue
  • Nausea
  • Organ failure with lung failure
  • ARDS
  • Kidney failure
  • Cardiovascular collapse or shock

How Have Cytokine Storms Been Treated in the Past?

Physicians have struggled to treat cytokine storms in the past. However, anti-inflammatory treatments have shown significant promise. For instance, anakinra, a treatment developed for patients with rheumatoid arthritis, has been shown to help treat cytokine storms in some clinical trials. Immunomodulators have also been used to help reduce the viral load, which is thought to be responsible for cytokine storms in the first place. Corticosteroids have also been used as an anti-inflammatory treatment and to treat symptoms of cytokine storms. However, no single treatment has shown to be particularly effective.

What Role Might Stem Cells Play in Treating Cytokine Storms?

Stem cells have proven anti-inflammatory capabilities, which makes them well-suited for treating cytokine storms stemming from COVID-19, as well as other conditions related to the disease. As mentioned by The New York Times,

"Certain kinds of stem cells can secrete anti-inflammatory molecules. Over the years, researchers have tried to use them as a treatment for cytokine storms, and now dozens of clinical trials are underway to see if they can help patients with COVID-19."

At this time, approximately 50 clinical trials are running that involve stem cells to treat COVID-19 symptoms. The sheer number of stem cell-focused trials is a testament to the immense potential offered by mesenchymal stem cells. However, the NYT cautions patients to temper their expectations, saying,

"But these stem cell treatments haven’t worked well in the past, and it’s not clear yet if they’ll work against the coronavirus."

With that being said, stem cell therapy is still very promising. As explained by the authors of the study, The pathogenesis and treatment of the Cytokine Storm in COVID-19, published in April 2020,

"As an important member of the stem cell family, mesenchymal stem cells (MSC) not only have the potential of self-renewal and multidirectional differentiation but also have strong anti-inflammatory and immune regulatory functions. MSC can inhibit the abnormal activation of T lymphocytes and macrophages, and induct their differentiation into regulatory T cell (Treg) subsets and anti-inflammatory macrophages, respectively. It can also inhibit the secretion of pro-inflammatory cytokines, such as IL-1, TNF-α, IL-6, IL-12, and IFN-γ, thereby reducing the occurrence of cytokine storms. At the same time, MSC can secrete IL-10, hepatocyte growth factor, keratinocyte growth factor, and VEGF to alleviate ARDS, regenerate and repair damaged lung tissues, and resist fibrosis. Therefore, many functions of MSC are expected to make it an effective method for the treatment of COVID-19."

Allogeneic vs. Autologous Stem Cells

One important note can be drawn from the list of current stem cell-related COVID-19 trials currently underway in the United States. The trials are split between allogeneic stem cells and autologous stem cells. Of the two, allogeneic stem cells perform better with fewer (or no) side effects. This is largely due to the differences between the two types of cells.

Autologous stem cells are sourced from the patient’s own body. This means that those cells are the same age as the patient, and have accumulated significant damage and wear during those decades of life. There is a potential for a negative immune system response when implanting those stem cells in the patient, as well.

Allogeneic stem cells, on the other hand, are sourced from umbilical cord blood and tissue. They’re free of defects and damage, and are highly energetic, allowing them to proliferate throughout the body faster and more easily transform into other cell types needed for healing and regeneration. They’re also immune system naïve and, as such, do not create negative effects when implanted.

A Promising Therapy

Stem cell therapy holds a great deal of promise for treating cytokine storms in COVID-19-positive patients. However, the FDA has not approved any stem cell therapy, and any such treatment should be considered experimental.


Coronavirus Drug and Treatment Tracker
The Role of MSC to Treat Coronavirus Pneumonia and ARDS
Clinical Trials Results: Stem Cell | COVID-19 | Phase 1, 2, 3, 4
The pathogenesis and treatment of the Cytokine Storm in COVID-19
Definition of Cytokine Storm
What causes a cytokine storm?
Playbook for stopping deadly cytokine storm syndrome

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