Why some people with COVID-19 have severe inflammation

Credit: CC0 Public Domain

In a recent study from the University of Pittsburgh and Cedars-Sinai, researchers found why some people with COVID-19 develop severe inflammation.

They found how the molecular structure and sequence of the SARS-CoV-2 spike protein—part of the virus that causes COVID-19—could be behind the inflammatory syndrome in infected patients.

The study is published in PNAS. One author is Moshe Arditi, M.D.

In the study, the team started searching for features of the SARS-CoV-2 virus that might be responsible for Multisystem Inflammatory Syndrome in Children (MIS-C), a condition that includes persistent fever and severe inflammation that can affect a host of bodily systems.

They created a computer model of the interaction between the SARS-CoV-2 viral spike protein and the receptors on human T cells, the foot soldiers of the immune system.

Under normal circumstances, T cells help the body fight off infection, but when these cells are activated in abnormally large quantities, as is the case with superantigens, they produce massive amounts of inflammatory cytokines—small proteins involved in immune system signaling—in what’s known as a “cytokine storm.”

Using this computer model, the team was able to see that a specific region on the spike protein with superantigenic features interacts with T cells.

Then, they compared this region to a bacterial protein that causes toxic shock syndrome and found striking similarities in both sequence and structure.

Importantly, the proposed SARS-CoV-2 superantigen showed a high affinity for binding T cell receptors—the first step toward touching off a runaway immune response.

The researchers also found that those who experienced severe symptoms had a T cell response similar to what is seen in people exposed to superantigens and very different from the T cell response in patients who had only mild symptoms.

They are now trying to search for and test antibodies specific to the SARS-CoV-2 superantigen, with the goal of developing therapies that treat MIS-C and cytokine storm in COVID-19 patients.

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