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. The mix of those 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 is mounting 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 percent accuracyHow close the measured value conforms to the correct value.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>accuracy.
By inspecting the body’s immune response at a molecular level, a research team has developed a new way to test patients for COVID-19First identified in 2019 in Wuhan, China, COVID-19, or Coronavirus disease 2019, (which was originally called "2019 novel coronavirus" or 2019-nCoV) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has spread globally, resulting in the 2019–22 coronavirus pandemic.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>COVID-19. Their method can potentially catch infections a matter of hours after exposure — far earlier than current COVID-19 tests can detect the virusA virus is a tiny infectious agent that is not considered a living organism. It consists of genetic material, either DNA or RNA, that is surrounded by a protein coat called a capsid. Some viruses also have an outer envelope made up of lipids that surrounds the capsid. Viruses can infect a wide range of organisms, including humans, animals, plants, and even bacteria. They rely on host cells to replicate and multiply, hijacking the cell's machinery to make copies of themselves. This process can cause damage to the host cell and lead to various diseases, ranging from mild to severe. Common viral infections include the flu, colds, HIV, and COVID-19. Vaccines and antiviral medications can help prevent and treat viral infections.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>virus — with near-perfect accuracy. The team describes their innovation, which is still in the early stages of development, in the February 27 issue of the journal Cell Reports<em>Cell Reports</em> is a peer-reviewed scientific journal that published research papers that report new biological insight across a broad range of disciplines within the life sciences. Established in 2012, it is the first open access journal published by Cell Press, an imprint of Elsevier.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>Cell Reports Methods.
Most existing COVID-19 tests “rely on the same principle, which is that you have accumulated a detectable amount of viral material, for example, in your nose,” says study lead author Frank Zhang, who worked on the project as a Flatiron research fellow at the Flatiron Institute’s Center for Computational Biology (CCB) in New York City. “That poses a challenge when it’s early in the infection time window and you haven’t accumulated a lot of viral material, or you’re asymptomatic.”
The new technique is instead based on how our bodies mount an immune response when invaded by SARS-CoV-2Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the official name of the virus strain that causes coronavirus disease (COVID-19). Previous to this name being adopted, it was commonly referred to as the 2019 novel coronavirus (2019-nCoV), the Wuhan coronavirus, or the Wuhan virus.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>SARS-CoV-2, the virus that causes COVID-19. When the assault starts, specific genes turn on. Segments of those genes produce mRNA molecules that guide the building of proteins. The particular blend of those mRNA molecules changes the types of proteins produced, including proteins involved in virus-fighting functions. The new method can confidently identify when the body is mounting an immune response to the COVID-19 virus by measuring the relative abundance of the various mRNA molecules. The new study is the first to use such an approach to diagnose an infectious disease.
An infographic explaining a new method for diagnosing patients with COVID-19. Credit: Lucy Reading-Ikkanda/Simons Foundation
The researchers tuned their method using 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.
When put to the test using real-world blood samples, the new method yielded an impressive 98.4 percent accuracy rating. That’s especially impressive as the approach works just as well on asymptomatic patients, for whom rapid antigen tests can be less than 60 percent 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’s a promising alternative and complementary approach to conventional PCR tests.”
The new approach isn’t ready for prime time yet, Zhang says. He and his colleagues only tested blood samples rather than the nasal samples that are more common and convenient 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 colds.
The researchers say they’re optimistic, though, as other research groups have already made progress on tests that look solely at which genes turn on. Those same tests could easily add the mRNA analysis developed in the new study, thereby producing even better results, Zhang says. “Anything they can do, we can probably explore and join forces on,” including catching cases within hours of initial exposure.
Reference: “Blood RNARibonucleic acid (RNA) is a polymeric molecule similar to DNA that is essential in various biological roles in coding, decoding, regulation and expression of genes. Both are nucleic acids, but unlike DNA, RNA is single-stranded. An RNA strand has a backbone made of alternating sugar (ribose) and phosphate groups. Attached to each sugar is one of four bases—adenine (A), uracil (U), cytosine (C), or guanine (G). Different types of RNA exist in the cell: messenger RNA (mRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA).” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>RNA alternative splicing events as diagnostic biomarkers for infectious disease” by Zijun Zhang, Natalie Sauerwald, Antonio Cappuccio, Irene Ramos, Venugopalan D. Nair, German Nudelman, Elena Zaslavsky, Yongchao Ge, Angelo Gaitas, Hui Ren, Joel Brockman, Jennifer Geis, Naveen Ramalingam, David King, Micah T. McClain, Christopher W. Woods, Ricardo Henao, Thomas W. Burke, Ephraim L. Tsalik, Carl W. Goforth, Rhonda A. Lizewski, Stephen E. Lizewski, Dawn L. Weir, Andrew G. Letizia, Stuart C. Sealfon and Olga G. Troyanskaya, 12 January 2023, Cell Reports Methods.
DOI: 10.1016/j.crmeth.2023.100395
Zhang worked on the computational aspects of the project along with CCB research fellow Natalie Sauerwald and CCB deputy director for genomics Olga Troyanskaya. Stuart Sealfon of the Icahn School of Medicine at Mount Sinai in New York City led the work on the study’s biological components, with Standard BioTools in San Francisco developing the testing setup.
Source: SciTechDaily
