Treatment for COVID-19-induced heart damage

COVID-19 vaccines are providing long-awaited hope, but they are not a ‘silver bullet’ to end the pandemic. As you may have read in Professor Sudha Rao’s opinion piece, we will require multiple tools in our toolbox to fight this insidious disease.

Peter was a 60-year-old Type 2 diabetic living in New York who in January 2021 contracted COVID-19. Peter was diagnosed with severe COVID-19 pneumonia, and was quickly intubated in hospital. His oxygen levels were a moving target, and he was treated with rendicivor and steroids over several weeks. Even with a ventilator, his oxygen levels and blood pressure kept dropping. At one point, it looked like Peter was going to pull through. His condition went from critical, to acute, to stable. He even started texting family and friends and sent a selfie from his hospital bed. The doctors believed him well enough for a tracheostomy, however just a day after the surgery, Peter suffered a cardiac arrest. The doctors tried to revive him, but nothing could be done.

There is still so much work to do with developing drug treatments to amplify the effectiveness of the vaccine, and to stop people from dying all over the world, and in Australia. While patients lungs are typically the site of damage, there are also those with COVID-19 complications including kidney and heart failure.

For those that are lucky enough to recover, there is a growing body of research that suggests up to two-thirds of patients who have recovered from severe COVID-19 will have experienced some form of heart inflammation or injury.

Our researchers have discovered some of the ways COVID-19 damages the heart, and identified a class of drugs that could potentially protect or reverse this cardiac injury.

In severe cases of COVID-19, the immune system overreacts to the infection, releasing inflammatory molecules called cytokines into the bloodstream. This so-called ‘cytokine storm’ can damage multiple organs, including the heart.

Canadian company Resverlogix has used QIMR Berghofer research findings as the
basis for expanding its clinical trial of the drug, apabetalone, in COVID-19 patients.

Apabetalone belongs to a new class of drugs that has been in clinical trials for cardiovascular disease for more than 3 years. It has received breakthrough therapy designation from the US regulator, the Food and Drug Administration. Resverlogix initially planned to study apabetalone to improve clinical status in SARS-CoV-2 infected patients, but will now also examine protection from heart damage in these patients.

The head of QIMR Berghofer’s Cardiac Bioengineering Research lab, Associate Professor James Hudson, said his team used thousands of lab-grown, miniature human heart organoids to understand how COVID-19 causes cardiac damage.

‘We wanted to find out exactly how the cytokine storm causes cardiac damage by identifying the proteins responsible, and then try to repurpose existing drugs targeting those proteins,’ Associate Professor Hudson said.

As he explained, ‘We thought understanding the biological basis of the heart damage was critical for identifying drugs with a much higher chance of success.

We exposed the bioengineered, stem-cell-derived heart tissue to COVID-19 patient blood and found it caused dysfunction even when the virus didn’t infect the tissue.

These experiments revealed which inflammatory factors are potentially causing the cardiac problems.

Researchers then used our mini heart organoids to screen several existing drugs that inhibit this protein and found they can prevent and reverse the damage.

One of these drugs was apabetalone, which was also effective at blocking the inflammatory response. Because it is already in phase III clinical trials for treating cardiovascular disease, it could be available sooner to treat COVID-19 patients.

It’s great to be working with Resverlogix to progress this research to a clinical trial to test if apabetalone can be safely used to prevent the terrible organ damage seen in COVID-19 patients around the world.’

The President and CEO of Resverlogix, Donald McCaffrey, said it had been a pleasure to work with the QIMR Berghofer team and stressed the importance of working together.

‘Collaborations such as this serve to quickly move our research forward for the benefit of patients.’

We at QIMR Berghofer are excited to see this research contributing to the expansion of a clinical trial, which we hope will help prevent heart injury in COVID-19 patients, in Australia and throughout the world, as we continue to battle the impact of the pandemic. 

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