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03 May 2023

Researchers uncover the key to fighting out of control inflammation in severe COVID-19 infection

New research into our immune system opens the door to new treatment that could prevent runaway inflammation in patients with severe COVID-19.

Macrophages are one of the most important cells of the immune system. While they play a central role in defending the human body against infection, they can also contribute to the excessive inflammation that characterises severe COVID-19 infections, and may also help facilitate viral replication and spread throughout the body.

In a study published in Science Signaling, scientists from the University of Queensland’s Institute for Molecular Bioscience (IMB) and the Peter Doherty Institute for Infection and Immunity (Doherty Institute) took a deep dive in the immune system to understand how macrophages interact with the SARS-CoV-2 virus.

They discovered that most macrophages are not infected with the virus. In fact, instead of triggering a protective, anti-viral response to eliminate the virus, uninfected macrophages detect damage and death in neighbouring cells and trigger a strong inflammatory response resulting in widespread inflammation.

The University of Queensland Dr Larisa Labzin, first author of the study, said that the problem is we end up with too many immune cells coming to the site of infection causing a whole lot of collateral damage – too much inflammation and not enough virus fighting.

“It's a double-edged sword for the body: the immune system tackling an infectious disease early on is protective, but when it's prolonged or excessive, it can really drive chronic inflammation,” Dr Labzin explained.

The University of Melbourne Dr Sarah Londrigan, Laboratory Head at the Doherty Institute and joint senior author of the research, said that this study reveals key differences in our immune response to SARS-CoV-2 compared to other respiratory viruses like influenza A virus.

“This finding that most macrophages (immune cells) are not infected with SARS-CoV-2 is in direct contrast to our ongoing studies with influenza A virus, which is able to infect these cells very well,” Dr Londrigan said.

“This information is another piece in the puzzle towards understanding why some respiratory viruses cause such severe disease.”

With the new understanding of how macrophages recognise and respond to the virus, researchers are investigating new therapeutic strategies to reduce the incidence of severe COVID.

Anti-inflammatory drugs are currently given to patients hospitalised with COVID-19 after the virus has peaked, to calm down the overactive immune response but the drugs make patients susceptible to secondary infections.

The key will be to develop treatment targeting macrophages without compromising the body’s ability to fight against the virus, like anti-inflammatories that can be administered earlier, to prevent inflammation getting out of control.

The University of Queensland Professor Kate Schroder, joint senior author of the paper, said understanding more of the fundamental biology behind the immune system will help us help our bodies fight more strongly against infections.

“We have vaccines and anti-virals in the fight against COVID-19 but the virus keeps mutating, so this is a way to future-proof ourselves against new variants and also future pandemics and infections.”

Dr Londrigan concluded that, while this work is the fruit of collaboration with the University of Queensland’s IMB and the Doherty Institute, other teams also played a crucial role in this research.

“I really want to acknowledge the important and ongoing collaborations between miney and Professor Kanta Subbarao’s teams with Associate Professor Daniel Steinfort and colleagues at the Royal Melbourne Hospital.”

Peer review: Science Signaling

Funding: National Health and Medical Research Council (NHMRC), Doherty Institute COVID-19 Agility Fund, National Heart Foundation of Australia