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Study finds possible cause of severe inflammation that increases death in COVID-19 patients

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As clinical evidence suggests that the most common cause of death in COVID-19 patients is a potentially fatal condition known as a cytokine storm, University of Alberta researchers have identified a protein in the blood that may be to blame.

The researchers discovered that COVID-19 patients have significantly higher levels of a protein known as galectin-9 in their blood plasma. Perhaps more importantly, they discovered a link between galectin-9 levels and pro-inflammatory cytokines released in the blood, which can cause a cytokine storm.

Shokrollah Elahi, an associate professor in the Division of Foundational Sciences at the School of Dentistry, led the study.

Elahi and his colleagues examined the blood plasma of 120 patients with COVID-19, building on their previous work with HIV, AIDS, and cancer patients. They discovered that galectin-9 levels were significantly higher in those patients than in HIV and cancer patients.

When they compared the levels of galectin-9 in COVID-19 patients to HIV and cancer patients, they were able to easily distinguish the COVID patients.

The findings suggest that galectin-9 levels in the blood could be used as a biomarker to diagnose COVID-19, potentially providing another non-invasive tool for COVID-19 testing. The levels could also be used to determine the severity of the disease, according to the author, though more research is needed in this area.

The discovery of elevated galectin-9 levels in COVID-19 patients is significant due to the protein’s positive correlation with a wide range of pro-inflammatory cytokines.

Cytokines, which are small cell-signaling proteins, play a role in immune system checks and balances; they can turn on or off certain cells to regulate the immune system. 

The problem in the context of COVID is that there is a dysregulation of cytokine production—they are released very quickly and at high levels. That is referred to as a cytokine storm.

By binding to immune cells and compelling them to produce pro-inflammatory cytokines in response to COVID-19 infection, the team discovered that galectin-9 is responsible for instructing immune cells to rapidly release pro-inflammatory cytokines.

Additionally, as tissues are damaged by inflammation, more galectin-9 is released from cells, activating additional immune cells and releasing additional cytokines in a vicious cycle.

The study explained that the resulting cytokine storm damages tissue and organs, causes severe inflammation, and can result in death. Even if patients survive the storm, immune dysregulation can have long-term consequences and may be associated with post-COVID-19 syndrome or long COVID.

The next step, according to the study’s author, is to develop treatments that block or inhibit the protein. While there are some compounds that may be used, such as lactose or anti-galectin-9 antibodies, there are currently no treatments available for blocking galectin-9 in humans.

The study was published in the American Society for Microbiology journal, mBio.

Image Credit: Angus Mordant/Bloomberg via Getty Images

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