A new method can quickly diagnose COVID-19 more accurately than existing approaches. The technique is based on how the body expresses genes in response to infections. When a gene is expressed, different segments of the gene create different mRNA isoforms. Mixing these isoforms changes the types of proteins produced, including proteins involved in fighting viruses. By measuring the relative abundance of various isoforms, the new method can confidently identify when the body mounts an immune response to the COVID-19 virus. Credit: Kouzou Sakai/Simons Foundation
By monitoring the body’s molecular response to a viral attack, the new method developed by Flatiron Institute researchers and their colleagues can diagnose even asymptomatic patients with 98.4%
Most of the existing COVID-19 tests “are based on the same principle, that you have accumulated a detectable amount of viral material, for example, in your nose”, explains the study’s lead author, Frank Zhang, who worked on the project as a Flatiron researcher. Fellow of the Flatiron Institute’s Center for Computational Biology (CCB) in New York. “It poses a challenge when it’s early in the time window for infection and you haven’t accumulated a lot of viral material, or you’re asymptomatic.”
The new technique is instead based on how our body mounts an immune response when invaded by 
An infographic explaining a new method for diagnosing patients with COVID-19. Credit: Lucy Reading-Ikkanda/Simons Foundation
The researchers adjusted their method using blood samples from a 2020 study of US Navy recruits taken before and after the participants caught COVID-19. The researchers’ computational framework identified more than 1,000 disease-associated mRNA variant ratio changes.
When tested using real blood samples, the new method yielded an impressive 98.4% accuracy rate. This is all the more impressive as the approach works so well on asymptomatic patients, for whom rapid antigen tests can be less than 60% accurate. “It was really surprising that it worked so well,” says Zhang, now an assistant professor at Cedars-Sinai Medical Center in Los Angeles. “It is a promising alternative and complementary approach to conventional PCR testing.”
The new approach isn’t ready for prime time yet, Zhang says. He and his colleagues only tested blood samples rather than the more common and practical nasal samples for diagnosing COVID-19. Also, they need to make sure they can distinguish between the body’s reaction to COVID-19 and its response to infections caused by other viruses, such as the common cold.
The researchers say they are optimistic, however, as other research groups have already made progress on tests that examine only which genes turn on. Those same tests could easily add the mRNA analysis developed in the new study, producing even better results, Zhang says. “Anything they can do, we can probably explore and join forces,” including finding cases within hours of initial exposure.
Reference: “Blood