People who escape the worst symptoms of COVID-19 infection may be having the right balance of a type of immune cell called macrophages, suggests a new study.

Since SARS-CoV-2 first began storming around the world in early 2020, COVID-19 has claimed six million lives and counting, according to the World Health Organization. And yet, the vast majority of people who have contracted COVID, some 99 per cent of the more than 500 million confirmed cases, have survived their brush with the disease.

The study of the COVID virus in the lung led by Boston University researchers suggests 11 "protection-defining genes" may have helped these people avoid the worst symptoms. White blood cells found in every tissue, macrophages, the guards of the immune system, are healers. Besides being crucial in wound repair, they also take on invaders, gobbling up and digesting anything that looks like it doesn't belong in the body, from dead cells to harmful bacteria.

Evidence has been growing that many COVID deaths are caused by a hyper-immune response: rampaging macrophages attacking not just the virus, but also our bodies, causing excessive inflammation and damaging heart and lung tissue.

In the study published in Cell Reports, researchers examined COVID's impact on those who get dangerously sick and those who don't. The findings could help efforts to develop new drugs that better prime immune systems for taking on the virus.

"If you can understand why most people are protected against COVID and how their body protects them, then you could potentially harness this knowledge to develop therapeutics and other advances," said Florian Douam, assistant professor of microbiology at BU's School of Medicine.

For the study, the team developed a new model with human lung tissue and bolstered it with a human immune system derived from stem cells, for monitoring the different stages of SARS-CoV-2 infection and COVID-19 disease.

"We were barely seeing any virus in the lungs. The lung was protected," Douam said, adding that's how they "found the macrophages". Further, the team found that with a more diverse macrophage population that has both regulatory and inflammatory macrophages, one could more effectively regulate the signals driving antiviral responses, shutting them off when appropriate.

The researchers tied this positive antiviral response to a set of 11 genes they called "protection-defining genes". In cases of effective resistance, these genes were working harder, or what's known as upregulated. Douam noted that the study helped them understand that "macrophages can promote protection in the lung tissue.

"We also know the key set of genes that these macrophages need to express to protect the lung," he said. But future studies are needed to understand why some people can put a diverse mix of macrophages to work while others can't.