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T Cell Immune Response and Cytokine Storm in COVID-19 Patients

February 2021

COVID-19

T Cells and COVID-19

The body is naturally equipped with a variety of T lymphocytes that work together to fend off harmful pathogens. The human immune system routinely battles mild diseases with recognizable antigens. By attacking the source of a virus or bacteria, damage to healthy cells can be minimized.

The T cell immune response to COVID-19 is different because it’s caused by an RNA virus (SARS-CoV-2). RNA viruses insert themselves into host cells and rapidly produce more molecules using the mechanisms of the healthy cell. This rapid duplication of cells also causes an increased mutation risk, making it difficult to generalize the treatment of a population.

Without help from any external agents, the immune system uses cytokines to combat infection. Cytokines are proteins released by cells that signal other cells to assist or retreat from a target area. Specific cytokines, called interferons (IFNs), are particularly important in their relationship to COVID-19. IFNs inhibit viral replication at the site of infected cells and therefore reduce the necessary immune response. When IFNs are not working properly, more and more cells will be called to deal with the virus, causing an inflammatory immune response. This inflammatory response can grow out of control and damage healthy cells in what’s called a cytokine storm.

What is a Cytokine Storm?

A cytokine storm occurs when excessive amounts of immune proteins are released into the body during an overwhelming inflammatory response. While this does not occur in all patients with severe COVID-19 symptoms, it is linked to many cases that result in related respiratory diseases. Those who experience a cytokine storm from SARS-CoV-2-related problems are more likely to die or suffer the most. This is because the chaos of cytokine storms results in the immune cells attacking healthy areas of the body.

In severe cases of COVID-19, cytokine storms are likely to occur in the lungs. These immunological misfires cause blood vessels to leak and clot. As blood pressure starts to plummet, other organs can fail as they aren’t receiving sufficient oxygen and other nutrients. If a cytokine storm is identified early in the process it can be treated with steroids and other immunosuppressants. However, if the immune system is dialed back too much, there will be no T cells to defend against the original virus.

COVID-19 Immune Response

Similar to other diseases, the body recognizes COVID-19 as a harmful foreign substance. Due to its unique RNA nature, the best way to combat the virus is by inhibiting the replication in infected host cells. The next part of the immune response is to remember the pathogen, making a repeated exposure less of a threat.

When it comes to developing a COVID-19 immunity, multiple types of T cells come into play. Assuming a successful immune response, the infected cell will undergo apoptosis, or internal cell death, and fragments of the virus will release into the surrounding bloodstream. These fragments have proteins on them that can bind to antigen-presenting cells (APCs). APCs code the proteins from the virus into receptors the immune system can recognize for future references.

APCs with coronavirus fragments on them can signal cytotoxic T cells to seek out and destroy any infected cells with the same protein. Helper T cells function in conjunction with APCs to release cytokines and hormones that trigger different levels of the immune response. Lastly, B cells that collide with the APCs or the free-floating protein fragments can attach to them and begin to form antibodies. When the B cells are activated by specialized helper T cells, the B cells release coronavirus antibodies that will mark the virus for destruction and block fragments from infecting other cells.

These differentiated cells can survive in the body and continue fighting pathogens for months. This is why those who recover from COVID-19 develop a temporary immunity.

COVID-19 Symptoms

COVID-19 can take a multitude of different forms. Although the list of possible related ailments is constantly being expanded, some are more common than others. Symptoms are often divided into three categories:

  • Mild: Low fever, sore throat, dry cough, and body aches.
  • Moderate: Fever above 100.4 F, shortness of breath, more persistent cough.
  • Severe: Constant chest pain or difficulty breathing, confusion, respiratory failure, trouble staying awake.

Those exposed to coronavirus can also be contagious without showing any of these symptoms. Somebody experiencing mild or moderate COVID-19 symptoms must take precautions to prevent the development of more severe symptoms.

Effect of T Cell Variations on COVID-19

Research on the coronavirus has led to the discovery that varying levels and types of T cells can have a significant impact on a patient’s response to the virus and to treatment. Depending on whether a patient has a depleted T cell count, a highly activated T cell population, or is immunodeficient, different outcomes are more likely than others.

Depleted

When an individual has fewer T cells than the average patient, they run a higher risk of not being able to control the COVID-19 virus naturally. T cell depletion can happen for a multitude of reasons, whether from another ailment or a genetic predisposition, and it hinders the immune system’s ability to fight all diseases. This makes it harder for the individual to fend off the virus and other illnesses simultaneously.

Highly Activated

Activation of T cells can be a good or bad thing. A high level of activation in helper T cells is observed in patients who have recovered from COVID-19. However, the previously mentioned cytokine storms are caused by over-activation of immune cells. Severe cases of COVID-19 can tamper with the antiviral mechanisms of a cell, causing a reduction in certain proteins, such as perforin. Perforin is released to create pores in a cell that ultimately leads to its death. When mechanisms like this are deterred or blocked, the over-activation of T cells can cause large numbers of lymphocytes to attack healthy cells nearby.

Immunodeficient

The term immunodeficient represents any faults in the immune system. Depleted numbers of T cells and overactive T cells are both immunodeficiencies. If the immune response is absent or at all compromised, a patient can be labeled as immunodeficient. Interestingly, the type of hindrance can make a difference in how the body handles coronavirus.

For example, research shows that a majority of patients who die or experience severe COVID-19 symptoms do so as a result of cytokine storms. Injuries such as acute respiratory distress syndrome that cause organ failure or fluid in the lungs that stem from COVID-19 are from the immune system attacking itself. This means that patients with highly-active immune systems—especially those that do not function properly—are at a greater risk of death or severe symptoms than those with more subdued immune responses.

However, it makes sense that those with depleted T cells or an immune system that doesn’t sustain a strong enough response are more likely to engage in a prolonged response that could leave the body exhausted, resulting in greater vulnerability to other diseases.

The Importance of Cell Separation

The way the immune system responds to COVID-19 depends on the level of exposure, the specific strand, and even the genome of the person who was exposed. Such a large variety of factors can have an impact on the effects of the disease. Even though vaccines are currently being administered, there continues to be aspects of this virus that mystify us and require more research. Studying T cells and how they react to COVID-19 is one of the primary strategies that scientists are using to gain additional insight to the virus.

Studying T cells can be an arduous task depending on the techniques a lab uses to isolate and separate them from unwanted peripheral mononuclear blood cells. Akadeum Life Sciences has developed an innovative technology that harnesses the buoyant properties of microbubbles to enable fast and incredibly gentle T cell enrichment that maintains the health and physiology of T cells of interest. Buoyancy-activated cell sorting, or BACS, is a simple and cost-effective way to get a highly-enriched population of T cells that are ready for downstream processing.

Studying T cells provides scientists with insight on how the virus actually behaves, and that information will put us closer to getting it under control.  Explore our line of T cell Isolation kits and discover the simple and elegant power of microbubbles, or view past webinars to get an in-depth look at the microbubble technology and how it’s being used to overcome existing barriers in sample preparation.

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