A team of scientists and doctors studied more than 150 rugby players at England’s highest level between 2017 and 2019, comparing saliva samples collected before the season with samples collected as players were assessed for concussions or an injury to another part of their body. The researchers found the genetic markers in saliva determined with 94 percent accuracy which players had been diagnosed with concussions and which had not, co-author and University of Birmingham professor Antonio Belli said.
At present, a diagnostic test for concussions does not exist. Doctors diagnose them by interpreting behavior, symptoms and, in a hospital setting, imaging tests. The new findings could change how concussions are diagnosed in sports and beyond, helping patients that range from football players to victims of traffic accidents to soldiers on a battlefield.
“It is now possible to accurately identify concussions simply by analyzing players' saliva, extending the ability to safeguard the brains of injured players outside professional ranks,” co-author Valentina Di Pietro said in an email.
The University of Birmingham team, with assistance from Rugby Football Union and Marker Diagnostics, relied on recent technological advances in gene sequencing. They used a statistical composite of 14 small non-coding RNAs (sncRNAs), which provide the cellular blueprint for certain proteins, to determine whether a player had suffered a concussion.
“What’s exciting about this is we not only found a very accurate way of identifying brain trauma, but also we found it in saliva, which is not invasive,” Belli said. “Everybody, including myself, has been looking at blood for many years. We’ve never really seen anything so exciting for mild traumatic brain injury.”
Two outside experts — Concussion Legacy Foundation co-founder Chris Nowinski and New York University director of neuropsychology William Barr — reviewed the study at The Post’s request before publication. Both said it relied on sound, strong science and represented exciting progress.
“Everybody is looking for a concussion test,” Barr said. “The diagnosis of concussions is really based on clinical findings. A lot of that is based on what a person reports. What we’ve always been looking for is: Is there something objective? Because, in a lot of cases, they’ll deny [feeling symptoms]. That’s what this really adds.”
For sports, the endpoint of the study would be an instant test that could be taken on the sideline to validate a trainer’s concussion diagnosis. Barr outlined how it could help in a familiar scenario: If a player resisted a physician’s concussion diagnosis, the physician could use a saliva test as validation.
“Is there something you can measure in a [sideline] time frame?” Marker Diagnostics research scientist Patrick O’Halloran, one of the researchers for the study, said during a virtual news conference. “This research demonstrates that, yes, you can measure it. There is a signal you can measure. The second component, then, is: Do you have the technology to actually measure it outside of a laboratory setting?”
Right now, there is not. It takes a working day to get test results. But researchers could find the technology in a handful of years or less — benefited indirectly by the coronavirus pandemic. O’Halloran said Marker scientists are discussing ways to make the instant test, an effort that may be expedited by advancements created in the past year as scientists sought more efficient and more accurate coronavirus tests.
Even without a sideline test, experts could see the testing making a major impact on the NFL. Nowinski envisioned testing every player after every game to identify players who suffered concussions but either did not know or were hiding symptoms.
“We know a significant share of concussions are not diagnosed during the game, and players may or may not report them after the game,” Nowinski said. “We could finally get to the bottom of how many concussions are being missed.”
A diagnostic concussion test also could improve how NFL teams handle players after they suffer a potential concussion. Nowinski pointed to the high-profile example of Kansas City Chiefs quarterback Patrick Mahomes in last season’s playoffs. Mahomes wobbled with glassy eyes after taking a hit around the neck and left the game. While he was placed in the concussion protocol, reports indicated the Chiefs never fully determined whether Mahomes had suffered a concussion. A test could have provided a more scientific determination, clarifying Mahomes’s recovery process.
One crucial aspect of the study is that only male rugby players were tested, which means more study is required before a test would be applicable for women, including female athletes. Research suggests women respond to and experience concussions differently than men, O’Halloran said, citing the specific example of differing inflammatory markers. Female and male athletes, he said, may have different sncRNA markers.
“The research we’re currently doing in female athletes may show us there’s some overlap, but it’s possible we’d just need a different modeling to diagnose female athletes compared to males,” O’Halloran said. “We don’t think it would be effective to try and transpose the markers found in male athletes based on what we’ve seen so far. We think of ourselves as being a step behind where we are with men’s athletes at the moment for female athletes.”
The Food and Drug Administration would need to approve any tests before they are used in the United States. The British researchers said they hope to submit a test for use in hospital settings for FDA approval in the near future.