A team of researchers has developed a method of monitoring the body’s molecular response to the SARS‑CoV‑2 virus that they believe can diagnose even asymptomatic patients with near-perfect accuracy.
The innovation, described on Monday in Cell Reports Methods, may also potentially catch infections hours after exposure -- far earlier than current COVID-19 tests used to detect the virus.
Most existing tests rely on the accumulation of a detectable amount of viral material in the nasal passages. However, this poses a challenge early in the infection when not much viral material has accumulated, and/or people are asymptomatic. The new technique is based instead on how the body's immune system expresses genes in response to an infection.
"The role of RNA alternative splicing in [host-response assays (HRAs)] remains unexplored, as existing HRAs are restricted to gene expression signatures," the authors wrote. "We report a computational framework for the identification, optimization, and evaluation of blood [alternative splicing]-based diagnostic assay development for infectious disease."
When invaded by SARS-CoV-2, the virus that causes COVID-19, specific genes turn on. Different segments of the genes create different mRNA molecules, called isoforms, that guide the building of proteins. The particular combination of those mRNA 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 identify when the body is mounting an immune response to the SARS-CoV-2 virus, and can diagnose COVID-19 sooner and more accurately than existing approaches. It works equally well on asymptomatic patients, for whom rapid antigen tests can be less than 60% accurate.
Using real-world blood samples from a 2020 study of U.S. Marine 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. The new method yielded an impressive 98.4% accuracy rating.
Since the researchers only utilized blood samples rather than the more common and convenient nasal samples used in most COVID-19 tests, the new approach is not yet ready for public use. Additional research is also needed to ensure that the test can distinguish between the body’s reaction to COVID-19 and infections caused by other viruses.
Other research groups are working on tests that look solely at which genes turn on following COVID-19 infection. The researchers say those tests could easily add the mRNA analysis developed in their new study, thereby producing even better results.
“It was really surprising that it worked so well,” said lead author Frank Zijun Zhang, PhD, in a statement. Zhang, a former Flatiron research fellow, now an assistant professor at Cedars-Sinai Medical Center, added, “It’s a promising alternative and complementary approach to conventional PCR tests."