Researchers have learned a lot about COVID-19 since the beginning of the pandemic, but there is still a lot we do not know. One of the things that makes this virus and the disease it causes so threatening is that, in some cases, the immune system becomes overreactive in response to this infection.

This abnormal immune response has been associated with more severe infection that can lead to long-term consequences and even prove fatal.

Normal Reaction

Most of the time, the immune system works like a fine-tuned machine, fixing, healing, and repairing the body. The process by which it does so is complicated, but it involves a balance of pro-inflammatory and anti-inflammatory responses.

Researchers are unsure why, but in people with severe COVID-19, these responses are unbalanced, resulting in excessive viral replication and inflammation.

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COVID Interferon Responses

Interferons are signaling proteins made by infected cells that warn other cells to increase their anti-viral efforts. Studies show that COVID alters the immune system's response by affecting interferons. This effect seems particularly damaging when it involves type I interferon. The Sars-Cov-2 virus seems to suppress type I, causing more inflammation.

Research shows that patients with a robust type I interferon response at the beginning of a COVID-19 infection clear the virus more effectively and quickly. A muted response often leads to severe, persisting disease.

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Sars-Cov-2 and Cytokines

Another way that COVID alters the normal immune response is by affecting the release of cytokines, proteins that allow the cells in the body to communicate.

When a Sars-Cov-2 infection affects the type I interferon and causes increased inflammation, the body releases a large number of pro-inflammatory cytokines, which cause widespread damage.

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Cytokine Storm

Researchers do not yet fully understand the mechanisms COVID uses to initiate a cytokine storm, but studies show a direct relationship between the number of pro-inflammatory cytokines in the blood and the severity of the infection. Experts believe that the virus uses an enzyme called ACE2 to enter the lungs, where it replicates rapidly while simultaneously releasing cytokines, leading to systemic inflammation and organ dysfunction.

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Multisystem Inflammatory Syndrome in Children

Multisystem inflammatory syndrome in children (MIS-C) is another example of what happens when COVID overtakes the immune system. While most children experience mild infections, those who develop MIS-C have severe inflammation in the organs and tissues, including the digestive system, skin, eyes, blood vessels, and brain.

Much is unknown about MIS-C, though researchers believe it results from an excessive immune response to COVID-19. Though it is rare, children with this syndrome can rapidly decline, which puts their lives at risk.

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Autoimmune Response

Time is of the essence when the immune system responds to the Sars-Cov-2 virus or any other invader, but it must also attack the right target. In some cases, COVID-19 makes the body attack itself.

While inflammation response is likely partially responsible for this reaction, studies also show that the body sometimes produces auto-antibodies that attack white blood cells, including B and T cells, which the body needs to kill the virus. Research also shows that these antibodies are not present at the beginning of the infection, indicating that the virus directly acts on the immune system to make them.

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Sluggish Response

Other research shows that some people may have a sluggish immune response from the innate immune system.

This system includes the physical barriers that prevent infection, like the skin and mucous membranes, and mobilizes the acquired immune system, which has a much more specific response. The innate immune system is inherited, meaning that some people have one that immediately recognizes and responds to the virus and others do not.

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Bacterial Debris

Researchers have also found bacterial debris in the blood of people with severe COVID-19. This debris consists of things like bacterial DNA and cell walls, and the more that is present in the blood, the more severe the infection.

Researchers believe that bacterial debris comes from beneficial bacteria in the lungs, throat, and intestines, implying that it is making its way into the bloodstream in severe infections and possibly increasing inflammation.

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Dendritic Cells

One study shows that COVID has a prolonged effect on dendritic cells, specialized immune system cells that play a role in immunity and stimulate the T cells that fight disease.

This study showed that COVID-19 survivors have a long-lasting reduction in dendritic cells, which may increase the risk of secondary infections and long-term management of symptoms.

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Long-Term Effects

COVID may have other long-term effects on immunity. Some researchers believe that lingering fatigue, pain, and neurological symptoms after infection may result from pieces of the virus hiding in the organs. These viral pieces may also trigger an excessive immune reaction and long-term inflammation, though the person is likely no longer able to infect other people.

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