DNA test to predict odds of severe COVID-19 draws scrutiny

scienceThe COVID-19 reporting by is supported by the Heising-Simons-Stiftung

Some people may want to know how vulnerable they are to severe COVID-19 before venturing into crowds.

PHOTO: APU GOMES / AFP / GETTY IMAGES

For people who haven’t yet been vaccinated against COVID-19 or are still nervous about venturing into crowds, the sales pitch can be tempting: drool in a tube to provide your DNA and mail it off to see How likely you are in the 10 to 15% of people who end up in hospital or die of SARS-CoV-2 infection. That’s the promise of a $ 175 test that an Australian company launched in the United States last week. It combines genetic data with a person’s age, gender, and previous medical history to predict their risk of getting extremely sick with COVID-19.

The company developed its test using data from thousands of COVID-19 patients in the UK. It could be a precursor to similar risk tests: an academic team recently detailed a simpler genetic test to determine how aggressively some people infected with SARS-CoV-2 should be treated.

However, several genetic experts warn that the influence of a person’s genes on the course of COVID-19 remains too unclear to conduct such risk assessments. “I think it is premature to use a genetic test to predict a person’s likely COVID-19 severity. We don’t understand exactly what these genetic variants mean or how they affect disease, ”says Johns Hopkins University genetic epidemiologist Priya Duggal.

Duggal and others also suggest that at a time when most people in the United States can get a highly potent COVID-19 vaccine, the company’s test may be pointless and even incentivize vaccination. People should get vaccinated, emphasizes Richard Allman, Chief Scientific Officer of Genetic Technologies from Melbourne, the developer of the test. But he says the test might be useful before immunity develops and later after it wears off.

The company relied on studies that combed the genomes of thousands of COVID-19 patients for common DNA base differences called single nucleotide polymorphisms (SNPs). For example, the genetic variants can affect a person’s resistance to the virus or susceptibility to a fatal immune overreaction. A global data pooling initiative called the COVID-19 Host Genetics Initiative has found tentative links between dozens of SNPs and a higher risk that an infected person will develop severe COVID-19 – from a doubling to a small increase, say 15% in risk to 16%.

Genetic Technologies included seven of the SNPs in a test after evaluating candidate markers using the UK Biobank, a research database of mostly white UK residents aged 50 to 84. The company compared about 2,200 of the biobank participants hospitalized for COVID-19 with 5,400 who had mild symptoms or no illness after infection. The test also takes into account COVID-19 risk factors such as old, male, obese, or diabetic.

The SNP-based result was a “significant improvement” in predictive power just using age and gender, the company concluded in a preliminary print in March. While the average risk of developing serious illness from the coronavirus for a person over 50 is 27%, it is only 4% for some people over 50, according to the company’s model. For others, says Genetic Technologies biostatistician Gillian Dite, the risk is “really, very high” – up to 98%, which means an unvaccinated person infected with SARS-CoV-2 is almost guaranteed to have severe COVID -19 developed.

However, the test debuts in a regulatory gray area. The Australian company and its US partner Infinity BiologX (IBX) have not applied for approval from the US Food and Drug Administration because, according to Allman, the test is not a direct product that requires regulatory review. After a customer has received the results of the IBX state-approved laboratories, they can contact a “telemedicine” doctor.

Several geneticists who have reviewed the company’s preprint indicate that the test needs to be checked in other, more diverse populations and possibly for new SARS-CoV-2 variants. “It’s a good start, but it’s by no means calibrated or validated enough to say this is a test I or my wife should take,” says cancer geneticist Stephen Chanock of the US National Cancer Institute.

Dite said it was difficult to find large datasets of clinical information on COVID-19 patients for additional validation and the company went “because of the importance of responding quickly to the pandemic”. The test asks if someone is of non-European descent, which appears to increase their risk of developing severe COVID-19, so it believes this is relevant to US minorities.

Members of the COVID-19 Host Genetics Initiative have proposed using only a single SNP on chromosome 3 to predict the risk of serious illness in infected people under 60 who seek medical help; A single copy of this SNP increases a person’s risk 2.6 times, the group reported in a preprint in March.

Even this single SNP test may not find medical application as quickly, says Amit Khera, a physician and scientist at Massachusetts General Hospital. “There are almost no examples” where doctors or emergency rooms give patients a rapid genetic test to guide treatment, he notes.

Still, many geneticists, including Chanock, who himself is looking for genetic risk factors for COVID-19, believe such tools are worth developing. But he states: “How and in what way such a test makes sense is still very open.”

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