Rare structural gene variants involved in body processes, like inflammation, which the virus needs to be successful, may explain the tremendous range of responses to infection with the COVID-19 virus from symptom-free to critically ill, suggests a research study.

"The virus has to attach to our cells, it has to get inside our cells and it has to multiply inside our cells. It also has to attract inflammation," said Dr Ravindra Kolhe, director of the Georgia Esoteric and Molecular Laboratory at the Medical College of Georgia at Augusta University.

"We have identified genes with structural changes in very sick individuals that are part of all four of these essential processes," he added. In the study, the team used optical genome mapping, to get a thorough, three-dimensional assessment of the genome of 52 severely ill patients with COVID-19.

In nine of the sickest patients, they identified seven rare structural variants affecting a total of 31 genes involved in key pathways mediating the response between a person, or host, and a virus.

These include innate immunity, our frontline immune defence against invaders like viruses, the inflammatory response, a key response to an infection that, gone awry, can also destroy the lungs of some of the sickest patients, and the ability of a virus to replicate and spread.

As an example, one variant they identified can lead to overexpression of keratin genes. Keratins are proteins that are the structural components of things like our hair and nails, but that also have been identified as key to the transmission of both flu viruses and the COVID virus between cells and are known to be upregulated in the respiratory tract during an infection.

"It's a hyperactivation of the normal systems," said Kolhe, in the study published in the journal Science. "Millions of people get infected, and fortunately only a very small percentage become symptomatic, and a very small percentage of the symptomatic individuals require oxygen and a small percentage of those individuals are hospitalised and die," Kolhe said. "But even a small percentage amounts to millions of people and that is too many."

"Our data show that large (structural variants) identified using optical genome mapping might further explain the inter-individual clinical variability in response to COVID-19," the researchers said.