Word that a saliva test can accurately identify whether an individual has sustained a concussion has created quite a buzz in recent weeks. The news comes from scientists at the University of Birmingham in the United Kingdom who studied saliva samples from some of the top rugby players in the country over the course of two seasons.1

Researchers compared saliva samples taken during the preseason with samples taken from players undergoing standard head injury assessments during regular season play. They also studied saliva samples taken from players assessed for injuries affecting other parts of the body.

They found specific micro RNAs or biomarkers in the saliva leave a distinctive signature for concussion, accurately identifying the players who were diagnosed with concussions with 94% accuracy.

Much of the discussion surrounding these findings has focused on how a saliva test could help sports coaches quickly determine when it is safe for athletes to safely return to active play following a blow to the head. Beyond the playing field, such a test would provide an important new tool to frontline providers in their assessments of patients who present to medical facilities with head injuries.

“Right now in the ED, we still don’t have a completely objective tool for diagnosing concussion,” explains Steven Hicks, MD, PhD, clinical director of the pediatric clinical research office at Penn State Health. “Imaging just helps you identify if [a patient is suffering from] a severe TBI [traumatic brain injury].”

Consequently, emergency clinicians must rely on largely subjective assessments and feedback from the patient. Particularly in the case of an athlete or student who wants to resume actively participating in sports, this type of feedback may not be entirely reliable.

That is why an objective measure could be critical in confirming or ruling out a concussion, a valuable supplement to subjective assessments and head injury protocols already in place. “You could potentially run a saliva sample or a blood sample, if someone replicates this work in blood, and have a supporting, objective answer within an hour or so of seeing a patient,” Hicks observes.

Consider Gender

The test out of the United Kingdom has received considerable attention, but the saliva-based test that Hicks and colleagues have been developing in the states for concussion works in a similar fashion.

“In terms of the technology used to measure the molecules in saliva, [the two tests] are pretty much the same,” he says. “The difference is the exact markers within each of our panels.”

Further, Hicks notes the U.K. researchers looked specifically at male athletes, so the results of their study are not generalizable to other populations yet. Conversely, in a study of their saliva test published in October 2020, Hicks and colleagues included a wider range of participants in terms of age, gender, and occupation. For instance, some participants had experienced military-related head trauma.2

“We were able to use the same algorithm to differentiate the concussed and the non-concussed participants in our study, whether they were male or female,” Hicks says. “Knowing how concussions can affect women differently than men — it is really important to ensure that your test works in both sexes.”

One strength of the U.K. study was the inclusion of a control group comprised of rugby athletes who had been hit in the head but were cleared through concussion exams and protocols. “A lot of studies out there will just use healthy controls,” Hicks notes. “I think that is one of the things that study did nicely that is likely to move the field forward.”

Expedite Results

Where do these saliva tests stand now? Hicks and colleagues received a large grant from the National Institutes of Health to validate the findings they published last year.3 “It is a three-year grant. It is specifically to develop a CLIA [Clinical Laboratory Improvement Amendments]-approved test,” Hicks says. “Our hope is to that within three years, we can develop an objective, saliva-based test for concussion. I think the group in the U.K. is probably working along a similar timeline.”

To make such a test practical and useful in the clinical setting and for coaches on the playing field, technology must be developed to analyze the saliva samples quickly. Hicks explains he and colleagues are already working with engineers at the Penn State College of Medicine to produce portable technology capable of meeting this need.

The U.K. research group is reportedly planning to submit a saliva test for use in hospital settings for FDA approval soon, although a precise timeline is unclear.4 The U.K. researchers also indicate they are conducting research with female athletes to see if the same test is effective at identifying concussion in women, or whether modifications are needed to produce a consistent level of accuracy.5 

REFERENCES

  1. Di Pietro V, O’Halloran P, Watson CN, et al. Unique diagnostic signatures of concussion in the saliva of male athletes: The Study of Concussion in Rugby Union through MicroRNAs (SCRUM). Br J Sports Med 2021 Mar 23;bjsports-2020-103274. doi: 10.1136/bjsports-2020-103274. [Online ahead of print].
  2. Hicks SD, Onks C, Kim RY, et al. Diagnosing mild traumatic brain injury using saliva RNA compared to cognitive and balance testing. Clin Transl Med 2020;10:e197.
  3. Quadrant Biosciences. Quadrant Biosciences awarded $2.3M NIH grant to develop rapid saliva test for concussion in children. Sept. 14, 2020.
  4. Kilgore A. Concussions can be diagnosed through a saliva test, British researchers find. The Washington Post. March 23, 2021.
  5. National Institute for Health Research. Rugby study led by the University of Birmingham through the NIHR SRMRC identifies new method to diagnose concussion using saliva. March 25, 2021.