Friday, June 19, 2020

Ch 5. A storm is coming - immunity to coronaviruses in context of COVID-19

What will this section talk about?
Cytokine storm, a hyper-immune reaction that can cause damage.

Readability grade 7
Reading time approximately 4:25 minutes

In the previous sections we have seen two possible outcomes. One, seen in majority of cases, is an appropriate immune response which eliminates the virus (Chapter 4). The other, if there is no or poor immune response to virus infection, virus overwhelms quickly causing death (Chapter 2). There is a third possible outcome which has gotten much attention and can also be problematic. This is an intense immune response to the virus called "cytokine storm", and damages organs. These outcomes are represented in figure below
Outcomes depending on immune response to virus infection

What other conditions can cytokine storm happen in?
The cytokine storm is an excessive and uncontrolled immune response. The abnormal immune response damages the health of the host and can lead to death. Besides COVID-19, it is also seen in other medical conditions. These other conditions can be other infections or non-infectious. Reports suggest that even some medications can be cause of cytokine storm. At the heart of the “cytokine storm”, are powerful chemicals called cytokines.

What do cytokines do?
The cells of immune system make cytokines for help with immune response. For example, an early immune cell will communicate with helper cell (Chapter 3) by cytokines. This signal may say to helper cell that infection is bacterial. The helper cells then, through different cytokines inform others (B-cells) to make antibodies. Thus, in the simplest of terms, cytokines are language, a communication between immune cells. Every unique immune cell type has its ability to signal and relaying it forward. A cytokine "storm" then is an excessive chaotic communication. This leads to hyper-activation and damage from this uncontrolled immune activity.

Are there different types of cytokines?
There are 5 major types of cytokines based on their function.
1. Some regulate early immune response, have anti-virus properties. (Interferons, discussed in Chapter 1)
2. Some promote inflammation. (Interleukins)
3. Some help direct movement of immune cells (Chemokines).
4. Some help different types of immune cells grow and survive (stimulating factors).
5. Some cause direct damage to diseased cells. A virus infected cell or cancer cells are examples. (tumor necrosis factor).

How does a cytokine storm start?
The start of a cytokine storm is local inflammation spilling over into the rest of the body. This happens by spreading of the immune cells and cytokines through blood. Many are familiar with the symptoms of local inflammation. For example, a local infection such an abscess or boil causes the affected part feels 1. Warm, there is 2. Redness, 3. Pain, 4. Swelling, and 5. Loss or reduced function. All 5 effects are results of immune system trying to remove the threat of local infection

How does a cytokine storm damage tissue?
In a rapid infection or an overstimulated immune system, the effects occur all over the body. Factors responsible for local symptoms spill over into other organs via blood. The lung and kidneys due to their high blood flows are at high risk from damage. Sepsis, a condition of excessive immune response to blood stream infection, is similar. In COVID-19, the lung gets affected three times. First, from infection of the virus in lung cells. Second, from immune response to kill the virus infected lung cells. Third, if cytokine storm occurs, immune damage to lung. This may be a basis for the severe and sudden cause of respiratory failure in COVID-19.

How common is a cytokine storm?
Cytokine storm is a less common outcome even in COVID-19 infection. Not every one will end up with a cytokine storm outcome. Evidence suggests genetic factors could increase or decrease the risk developing cytokine storm. These genetic differences are in genes responsible for “danger signal” detection (Chapter 1 and Chapter 3) , or cytokine production.

How can a cytokine storm be treated?
At present most treatment is symptom based. The goal of treatment for cytokine storm is to support vital organs like circulation (heart pump machine), respiratory (ventilators), kidneys (dialysis) etc until body recovers. Some medications like dexamethasone are corticosteroids (commonly known as steroids) and have shown benefit by calming down inflammation from over active immune system. Other medications to block cytokines are also available but their benefit is not clear.

Previous section: Ch 4. A favorable outcome - immunity to coronaviruses in context of COVID-19
Next Section: Ch 6. Candidate treatments for COVID-19 infection
List of all chapters 

Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, Katze MG. Into the eye of the cytokine storm. Microbiol. Mol. Biol. Rev.. 2012 Mar 1;76(1):16-32.

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