Calming the cytokine storm

Fall 2020

In severe cases, COVID-19 causes a patient’s immune system to go into overdrive. Termed the ‘cytokine storm,’ this creates hyperinflammation which wreaks havoc on the body. While therapies are currently limited, researchers at Lawson Health Research Institute are exploring novel treatments that could calm the cytokine storm and improve patient outcomes.

Treating COVID-19 using specialized dialysis

Researchers are using a modified dialysis machine to treat critically ill COVID-19 patients at London Health Sciences Centre (LHSC).

Dialysis machines, called dialyzers, are known for filtering and purifying the blood of patients with chronic kidney disease. This new study uses a modified version of a dialyzer called an extracorporeal leukocyte modifying device. It gently removes the patient’s blood, targets and transforms white blood cells associated with inflammation, and then releases those cells back to circulation. The hope is that these ‘reprogrammed’ cells will now fight hyperinflammation - rather than promoting it - in affected organs like the lungs.

“Working in the intensive care unit (ICU), I was acutely aware that more treatment options were needed in the fight against COVID-19,” says Dr. Chris McIntyre, Lawson Scientist and LHSC Nephrologist. “This led us to consider treating a patient’s blood outside of the body. If successful, we could alter the immune response by reprogramming white blood cells associated with inflammation.”

The clinical trial will include up to 40 critically ill patients at LHSC’s Victoria Hospital and University Hospital. Research participants will be randomized to receive either standard supportive care or standard supportive care in combination with this novel therapy. The research team will compare patient outcomes to determine if the new treatment is effective.

“The ultimate goal is to improve patient survival and lessen their dependency on oxygen and ventilation,” explains Dr. McIntyre. “If effective, it’s possible that this treatment could be combined with other therapies. For example, this could be used to reduce inflammation while an antiviral drug is used to fight the virus.”

Harnessing a human protein to treat sepsis

For the most severely ill COVID-19 patients, hyperinflammation can lead to sepsis, acute respiratory distress syndrome (ARDS) and multi-organ failure, all of which can ultimately result in death.

“Sepsis is a life-threatening condition associated with hyperinflammation,” says Dr. Claudio Martin, Associate Scientist at Lawson and Intensive Care Physician at LHSC. “Many critically ill COVID-19 patients develop sepsis one to two days before ARDS, suggesting that sepsis is a major contributor to the development of respiratory and multi-organ failure.”

In another trial, Dr. Martin is collaborating with his colleagues to study a manufactured form of annexin A5 – a human protein that has strong anti-inflammatory properties – as a potential therapy for COVID-19 patients with sepsis.

Patients will be randomized to receive either the drug at two different doses or a placebo. Their outcomes will be compared to assess whether the drug is effective.

“The ultimate goal is to determine whether this drug reduces the respiratory and multi-organ failure associated with sepsis in COVID-19 patients,” explains Dr. Martin.

The team also suspects that annexin A5 could reduce the formation of blood clots in COVID-19 patients – occurring as a result of the cytokine storm – by coating the inside of injured blood vessels.

This is the first time annexin A5 will be tested as a potential sepsis treatment in patients with COVID-19. The research builds on findings of a preclinical study from Dr. Qingping Feng, Lawson Scientist. His team previously found that annexin A5 can inhibit inflammation and improve organ function and survival when treating sepsis in animal models.

“Annexin A5 is a naturally-occurring protein with great potential as a therapy for sepsis, whether caused by COVID-19 or a different infection,” says Dr. Feng, co-investigator on the project. “If our initial trial is successful, we hope to run a large multi-centre trial to further examine the drug’s potential as a sepsis treatment.”

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Dr. Chris McIntyre