Organ-on-a-Chip Platform Helps Devise Strategy to Treat Severe COVID-19 Complications

They happen when the body releases a large number of signaling proteins called cytokines in the blood. Too many cytokines push the immune system into overdrive and can lead to vascular complications, multi-organ failure and even death. One of the greatest challenges for clinicians during the COVID-19 pandemic has been to understand why some people infected by the SARS-CoV-2 virus experience cytokine storms, while others do not. Using their novel organ-on-a-chip platform, researchers have now identified a molecule with the potential to combat cytokine storms, one of the most severe complications of COVID-19 infections.

The research team at the University of Toronto (Ontario, Canada) leveraged their expertise in organ-on-a-chip technology to identify the molecule, a novel anti-inflammatory peptide called QHREDGS that does not act on the virus directly. Instead, it works to prevent cytokine storm, a potentially life-threatening immune reaction. The team comprises experts in growing functional cardiac tissue outside the human body. These lab-grown tissues allow researchers to model diseases and understand how genetic mutations in cardiac tissues can cause cardiac failures.

The research team had recently carried out a study using a specific model tissue platform known as integrated vasculature for assessing dynamic events (InVADE). Using the InVADE platform, they infected a microfabricated perfusable blood vessel-on-a-chip with SARS-CoV-2 to understand how the virus triggers inflammation and vascular dysfunction. They also screened five compounds with anti-inflammatory properties that had been previously tested by clinicians to see if any of them showed promise in preventing the cytokine storm.

QHREDGS is a peptide that had previously been found to improve cardiomyocyte metabolism and enhance endothelial cell survival. In the study, the researchers found that it enhanced vascular functions and repaired the harmful effects of SARS-CoV-2. For example, the function of a vascular structure known as the endothelial barrier was improved by 62% compared with endothelial cells without the peptide, and the secretion of some cytokine storm molecules had been decreased between 1,000 to 10,000 times.

The InVADE platform is being used for many other investigations by the researchers, including a study that explores why cancer is rarely found in the heart. The team is also using the vasculature-on-a-chip system to better understand the causes of myocarditis that have been seen in COVID-19 patients, as well as in some individuals who have been vaccinated against the disease. The team is currently collaborating with other clinicians and researchers to find unique biomolecular markers associated with myocarditis. The researchers hope this type of organ-on-a-chip system will enable researchers to predict and better respond to future public health events.

“During the pandemic, we repurposed our cardiac tissue platforms to understand how the SARS-CoV-2 virus can cause vascular dysfunction,” said Rick Lu, a PhD candidate. “Vascular dysfunction can allow SARS-CoV-2 to penetrate into a person’s organs, such as the heart, liver and intestine. By improving vascular function and reducing inflammation in the body, we hope to prevent the kind of organ failure that has been seen in COVID-19 patients.”

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