A new study by Mater Research and University of Queensland scientists has identified a key cause of severe COVID-19 infections and paved the way for an entirely new treatment of the disease.
The researchers tested an existing drug which blocks cholesterol receptors on immune cells and found that it significantly lessens the severity of the disease in mice infected with SARS-CoV-2. The drug also significantly reduced viral loads in the mice.
Associate Professor Katharina Ronacher of Mater Research said the study was a “very significant” step towards developing a successful new treatment for both existing and future variants of COVID-19.
“The problem we now face when treating COVID-19 is that drug-resistant variants are emerging,” Dr Ronacher said.
“However, this drug is not an anti-viral – it does not attack the virus.
“It works by targeting the host’s own immune system and could be used as new viral variants emerge that are resistant to anti-viral drugs.
“This is a very exciting study; one which we hope could significantly improve the future treatment of patients with severe COVID-19.”
Associate Professor Katharina Ronacher and her team, PhD student Cheng Xiang Foo and post-doctoral fellow Dr Stacey Bartlett (pictured), found that SARS-CoV-2 infection triggers the production of oxidised cholesterols, which in turn cause immune cells to migrate to the lung via a cholesterol-sensing receptor named GPR183.
While immune cells are important to fight the infection, excessive infiltration of inflammatory cells known as macrophages (white blood cells which eliminate foreign substances) is a hallmark of severe COVID-19.
The researchers tested a drug that blocks GPR183 on immune and inflammatory cells and found that this drug specifically reduced infiltration of macrophages into the lung of SARS-CoV-2 infected mice.
Mice that received the treatment had less inflammation in the lung, significantly lower viral loads and overall less severe disease compared to mice receiving a placebo.
To determine whether oxidised cholesterols play a role in human COVID-19, the researchers analysed immune cells collected from the lungs of healthy controls and COVID-19 patients with moderate and severe disease.
They found that the enzymes that produce the oxidised cholesterols and the cholesterol receptor are significantly elevated in COVID-19 patients and are especially associated with severe cases of COVID-19.
“This suggests that the drug will also be effective in humans and warrants human clinical trials,” Dr Ronacher said.
The team’s study, ‘GPR183 antagonism reduces macrophage infiltration in influenza and SARS-CoV-2 infection’, has just been published in the prestigious European Respiratory Journal.
The study was a collaboration between Mater Research, The University of Queensland and the University of Copenhagen and was funded by the Mater Foundation, the Australian Infectious Disease Research Centre and Diabetes Australia.
It is hoped that clinical trials of the oxysterol receptor drug will be undertaken by the pharmaceutical industry, while Associate Professor Ronacher’s team will continue research into how the drug reduces viral loads in mice.
