Would you like to have your DNA tested to predict how hard COVID-19 would hit? Should you? | Science

The pandemic coronavirus only makes a few of the people it infects seriously ill, and one company says its saliva test can predict who is most at risk.

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By Jocelyn Kaiser

ScienceThe COVID-19 reporting is supported by the Heising-Simons Foundation.

For people not yet vaccinated against COVID-19 or still nervous about venturing into a crowd, the sales pitch can be appealing: drool in a tube to provide your DNA and send it by mail. to see how likely you are to be among the 10% to 15% of people who will end up in hospital or die from a SARS-CoV-2 infection. That’s the promise of a test that an Australian company launched last week in the United States. It combines genetic data with a person’s age, gender, and pre-existing medical conditions to predict their risk of becoming extremely ill from COVID-19.

The $ 175 test is based on genetic markers linked to severe COVID-19, as well as other risk factors, and the company says it developed its predictions using data from thousands of COVID-19 patients at UK. This may be a precursor to similar risk tests: An academic team recently detailed a simpler genetic test to help determine how aggressively some people with SARS-CoV-2 should be treated.

Yet several genetics experts say Science that how a person’s genes influence the course of COVID-19 remains too obscure to deploy such risk assessments. “I think it’s premature to use a genetic test to predict the likely severity of a person’s COVID-19. We don’t understand exactly what these genetic variants mean or how they affect the disease, ”says genetic epidemiologist Priya Duggal of Johns Hopkins University. She doesn’t think clinicians would change the way they treat an infected person based on these tests. And she hopes unvaccinated people wouldn’t engage in riskier behavior if the company’s test suggested they are less vulnerable to COVID-19.

Duggal and others also say the company’s test could be unnecessary at a time when most Americans can get a highly effective COVID-19 vaccine, or even deter some from getting the vaccine. Richard Allman, scientific director of the company behind the test, Melbourne-based Genetic Technologies, said people should heed public messages to get vaccinated, but adds that the test could also come in handy before as immunity does develop and later after its decline.

Genetic Technologies, which previously focused on cancer risk testing, developed the new test based on studies examining the DNA of thousands of COVID-19 patients for genetic variants that could help explain how much they got sick. The variants can influence a person’s resistance to the virus, for example, or their susceptibility to an excessive and fatal immune response. A global data-pooling effort called the COVID-19 Host Genetics Initiative has found tentative links between dozens of common genetic markers, basic differences in DNA called single nucleotide polymorphisms (SNPs), and higher risk than an infected person develops severe covid-19. – from doubling the risk to small increases, say from 15% risk to 16%.

Seven SNPs unearthed by the initiative form the basis of the new test. To narrow them down from a larger list of applicants, the developers at Genetic Technologies turned to data from UK Biobank, a research database made up mostly of white UK residents aged 50 to 84 who have provided medical information and had their DNA analyzed for thousands of people. of known SNPS. The company compared around 2,200 UK biobank participants who had been hospitalized with COVID-19 with 5,400 who also had the virus but ended up with mild symptoms or no illness. He was combining information about their SNPs with other risk factors for severe COVID-19, such as being elderly, male, obese, or diabetic.

The result was a “substantial improvement” in predictive power over using age and gender alone, the company concluded in a report. preprint posted in March. While the average risk of serious illness from the coronavirus for someone 50 or older is 27%, it is as low as 4% for some people over 50, the company’s model suggests. For others, according to biostatistician and first author of Genetic Technologies, Gillian Dite, the risk is “really, really high” – up to 98%, which means that an unvaccinated person infected with SARS-CoV – 2 is almost guaranteed to develop severe COVID-19.

Infinity BiologiX (IBX), the US partner of Genetic Technologies, now offers the test to adults 18 years and older. “By understanding who among us is most at risk of developing a serious illness, we can be more attentive to the safety protocols and the personal risks we are willing to take for ourselves and our loved ones,” the company explains on the IBX website. Even with the vaccine rollout, “companies would find this to be a valuable tool” for prioritizing unvaccinated people who could return to the workplace, Allman says.

However, the test begins in a regulatory gray area. The two companies did not seek U.S. Food and Drug Administration (FDA) approval for the validity of the test because, according to Allman, it is not a direct-to-consumer product that falls under its review. . Once a client has received results from federally approved labs from IBX, they may see a “telehealth” physician. But the FDA has at times exercised its authority over genetic risk tests ordered by consumers, as many of the the personal genomics society 23 & Me. (The FDA did not respond to a request for comment.)

Several geneticists who reviewed the company’s pre-release said Science the test must be validated in other populations more diverse than those detailed in the UK Biobank. They also wonder if his predictions are reliable for people infected with new variants of SARS-CoV-2. “It’s a good start, but it’s by no means calibrated or validated enough to say it’s a test I would take or my wife should take,” says cancer geneticist Stephen Chanock of the US National Cancer Institute, which is aware of other companies working on a similar test.

Said says it has been difficult to find large datasets with clinical information on COVID-19 patients. Her company has decided to go ahead, she adds, “because we don’t know when further validation will be possible, and because of the importance of a rapid response to the ongoing pandemic” . The test asks if anyone is of non-European ancestry, which suggests the data increases the risk of severe COVID-19, so Dite believes this is relevant to American minorities.

Some members of the COVID-19 Host Genetics Initiative have proposed using a single SNP on chromosome 3 to predict the risk of serious illness in infected people under the age of 60 who seek medical attention; one version of this SNP increases a person’s risk 2.6 times, they report in a preprint posted in March. (The authors declined to discuss the study until it was published in a journal.)

The study is “well designed,” says Massachusetts General Hospital physician-researcher Amit Khera, who combines SNPs into polygenic risk scores that attempt to gauge a person’s chances of developing common illnesses. Still, that doesn’t mean that a chromosome 3 SNP test will quickly find medical use, Khera adds. “There are hardly any examples” of doctors or emergency room staff giving patients rapid genetic testing to guide treatment, he notes. “I don’t think this is very likely to be implemented in practice.”

Yet many geneticists, including Chanock, who himself researches genetic risk factors for COVID-19, believe such tools are worth developing. But, Chanock notes: “How and in what way a test like this is going to be useful is still an open question.”


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