Identify the cause and potential treatment of heart damage induced by COVID-19

QIMR Berghofer 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 heart damage.

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 several organs, including the heart.

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

Apabetalone belongs to a new class of drugs that has been in clinical trials for cardiovascular disease for more than five years. It received the Revolutionary Therapy designation from the US regulator, the Food and Drug Administration. Resverlogix originally planned to study apabetalone to improve the clinical condition of patients with SARS-CoV-2, but will now also consider whether it can treat heart damage.

The head of QIMR Berghofer’s cardiac bioengineering research group, Associate Professor James Hudson, said his team had used thousands of laboratory-grown miniature human cardiac organoids to understand how COVID-19 causes damage cardiac.

“We wanted to find out exactly how the cytokine storm is causing heart damage by identifying the responsible proteins, and then trying to reuse existing drugs targeting those proteins,” Associate Professor Hudson said.

“We thought that understanding the biological basis of heart damage was essential to identify drugs with a much higher chance of success.

“We exposed the bioengineered heart tissue derived from stem cells to the blood of the COVID-19 patient and found that it caused dysfunction even when the virus did not infect the tissue.

“These experiments revealed which inflammatory factors are potentially causing heart problems. These factors activate the bromodomain 4 protein in the heart, which we have found to be the primary driver of damage from the cytokine storm.

“We then used our cardiac mini-organoids to screen several existing drugs that inhibit this protein and found that they could prevent and reverse the damage.

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

Associate Professor Hudson said laboratory tests have shown that apabetalone also decreases the expression of the ACE2 receptor protein, which is found on the surface of cells and is used by the SARS-CoV-2 virus to infect cells. cells.

“Inhibition of ACE2 receptor expression with apabetalone also led to weaker viral infection, which in turn decreased heart damage in our laboratory experiments,” he said.

“It’s great to work with Resverlogix to advance this research into a clinical trial to test whether apabetalone can be used safely to prevent the terrible organ damage seen in COVID-19 patients around the world.”

Resverlogix President and CEO Donald McCaffrey said it has been a pleasure working with the QIMR Berghofer team.

“We are delighted to finally be able to publicly share some of the incredible early results of our collaborative COVID-19 research program,” said McCaffrey.

“Apabetalone treatment not only reduces SARS-CoV-2 infection in cardiomyocytes, it also prevents cardiac dysfunction induced by the cytokine storm.

“These results present the unique dual mechanism of apabetalone as a potential treatment for COVID-19 and provide strong support for human clinical trials.

“Collaborations like this allow us to rapidly advance our research for the benefit of patients.”

Australian Health Minister Greg Hunt said it was gratifying to see research funded by the Medical Research Future Fund (MRFF) helping identify potential new treatments for COVID-19.

“We have ramped up funding for the MRFF to help Australian researchers contribute to the global effort against this disease,” Hunt said.

“It’s wonderful to see this research contributing to the expansion of a clinical trial, which I hope will help prevent heart injuries in COVID-19 patients.”

Queensland Minister of Health Yvette D’Ath said the state had provided Professor Hudson’s team nearly $ 1 million to continue their research to find new treatments for COVID-19 .

“Professor Hudson’s cardiac organoid research is world-leading and provides a way to quickly test potential new drugs,” Ms. D’Ath said.

“We are fortunate to have world leaders in this area of ​​research working in our state, and the Queensland government is proud to support this research.”

A growing body of research suggests that up to two-thirds of patients who have recovered from severe COVID-19 have experienced heart inflammation. About a quarter of patients hospitalized with severe COVID-19 have suffered some form of cardiovascular injury.

Professor Hudson’s research results have been posted on the pre-print server, bioRxiv, at the request of the scientific journal.

Provided by QIMR Berghofer Medical Research Institute