Imagine taking a genetic test that can tell you about your risk of complications and death from a particular disease, such as cancer, heart disease, or COVID. A translation of such tests is available — though incomplete.
Genome-wide association (GWAS) studies are increasingly common to assess COVID risk. This technique has the potential to fight the disease by identifying areas, or loci, in the human genome that put a person at a higher or lower risk of serious illness. Scientists hope that it may eventually open the door to new therapies.
“The genome sequence allows you to examine every single base in the genome,” said Athanasios Kousathanas, chief scientist of genomics data at the London-based company Genomics England. “And this allows you to identify genes that may be involved with high accuracy.”
However, some experts warn that GWAS alone is not enough to assess the risks of COVID accurately. They argue that genomic analysis may be challenging to break free from harmful substances in society and leave health systems vulnerable to discrimination.
Manuel Ferreira, a researcher at the genetic company Regeneron, is part of a team that uses GWAS to hunt down COVID-related areas by filtering out thousands of genomes in four integrated databases. In their most recent study, published in March in Nature Genetics, Ferreira and his co-authors combined the numbers and found that people with rare ACE2 levels appeared to be at 40 percent lower risk than most people with severe seizures. COVID. “This is the ‘strong effect,'” Ferreira said.
The ACE2 gene encapsulates the specific ACE2 protein found in the cell. Protein often helps control blood pressure and inflammation by allowing specific proteins to enter or leave the cell. But it also provides SARS-CoV-2, the old COVID virus, a cellular entry point for infection. When the virus interacts with the ACE2 protein, it attaches itself to its external protein as a burr snatched from a sock. From there, the virus enters the target cell.
But Ferreira found that people with genetic variants of ACE2 had less than 39 percent protein receptors in the cell membranes. Researchers speculate that, as a result, fewer SARS-CoV-2 viruses have been able to invade these bodies, significantly reducing their risk of severe COVID. “Somehow, it is not surprising at all, because we know that this virus needs [these] receptors to enter the cell,” Ferreira said.
Kenneth Baillie, a research doctor at the University of Edinburgh, recently collaborated with Kousathanas of Genomics England on a study that identified 16 new areas linked to COVID’s high risk. Others, Baillie believes, are more likely to be victims of new therapies. “I am convinced that there are many medical targets that we do not fully understand biology to date,” he said.
But some researchers warn that when predicting severe COVID, it is almost impossible to differentiate genetic risks from social risk factors such as access to health care and working conditions, even using genome-wide analysis.
Elsie Taveras is a pediatrician at Massachusetts General Hospital. But when the epidemic hit, he – like many others in his field – was rushed to the intensive care unit to help treat the flow of patients. Suddenly, he saw a pattern among those with severe COVID: Most were people of color from low-income communities, and many did not speak English.
“I never thought that the most important thing I could bring to the caregiver team was not my medical skills,” Taveras said. “I was able to attend because I could help the group with my Spanish.”