Salivary MicroRNAs: A Promising Biomarker for Persistent Post-concussive Symptoms in Children With Concussion

Salivary MicroRNAs: A Promising Biomarker for Persistent Post-concussive Symptoms in Children With Concussion 1024 768 Lauren Dembeck

The multidisciplinary study used children’s saliva and genomic analysis to identify promising biomarkers for persistent post-concussive symptoms.

Predicting clinical recovery of children with concussion is challenging. While concussion symptoms typically resolve within one to three weeks, up to one-third of children develop persistent post-concussive symptoms (PPCS), including headache, nausea, dizziness, blurred vision, and sensitivity to light and/or sound. Compared with children without PPCS, children with PPCS are at increased risk of experiencing disruption to their daily routines and functioning, such as missed school days, depressed mood, loss of social activities, leading to lower quality of life.

“The diagnosis of concussion is based on self-report,” explains senior author Jingzhen Ginger Yang, PhD, MPH, a principal investigator at the Center for Injury Research and Policy of the Abigail Wexner Research Institute at Nationwide Children’s Hospital. “Currently, there are no biomarkers to objectively predict who is going to recover sooner or later. If physicians could identify children at risk for prolonged recovery, they may be able to intervene earlier, providing personalized concussion care, to improve patient recovery.”

A growing body of literature suggests that salivary microRNAs – small single-stranded non-coding RNA molecules that regulate post-transcriptional gene expression – may serve as potential biomarkers to identify children with concussion who are at increased risk of PPCS. However, no studies have focused exclusively on children, and it remains unknown whether and how salivary miRNA expression levels differ over time between children with or without PPCS.

Using longitudinal assessment of microRNAs, Dr. Yang and colleagues demonstrated that the expression levels of 13 salivary microRNAs differ over time following concussion in children with versus without PPCS. The findings are published in Frontiers in Public Health.

To identify microRNAs and evaluate their predictive value in children with concussion, the researchers conducted a prospective cohort study. With parental consent, the team recruited 60 children between 11 and 17 years of age who were diagnosed with a concussion by a physician at Nationwide Children’s. They collected saliva at up to three timepoints (within one week of injury, one to two weeks post-injury, and four-weeks post-injury) and participants’ daily post-concussion symptom ratings throughout their enrollment using the Post-concussion Symptom Scale. PPCS was defined as symptoms (score ≥ 5) that persist at 28 days post-concussion.

“Concussion is a type of brain injury, and it can be difficult for children, especially those who are very young, to describe their symptoms following injury,” says Dr. Yang.

“The approach we used for sample collection is very promising because it is noninvasive and easy, for both the investigator and the patient, to collect the sample.  The lack of pain and convenience is appealing to families,” explains co-first author James MacDonald, MD, MPH, a physician for Nationwide Children’s Division of Sports Medicine.

The researchers measured expression levels of 827 salivary microRNAs in 135 saliva samples collected from the 60 children. They compared the longitudinal expression levels of the microRNAs in children with versus without PPCS using statistical models with repeated measures. Of the 827 microRNAs analyzed, the team identified 91 that had expression levels above a background threshold, and of those 91 microRNAs, they identified 13 with significantly different expression levels across the three timepoints post-concussion between children with and without PPCS.

“This research is an excellent example of the team science approach and what can be accomplished with multidisciplinary collaborations,” adds co-first author Katherine Miller, PhD, a principal investigator in the Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children’s. “The project required access to the genomic analysis technologies and assistance from the technical experts and biostatisticians. It also involved coordination and collaboration with the emergency department physicians and neurologists to diagnose concussions and collect samples. Most importantly, we also needed the patients and their parents or caretakers, who arrived at the emergency department at various times following injury, to consent and volunteer to participate in the study.”

“Everyone on our team was dedicated and contributed to the success of this study,” says Dr. Yang, who is also a professor of Pediatrics at The Ohio State University College of Medicine. “We put together the individual expertise of all the team members to come out with something greater.”

Among the 13 microRNAs identified by the team, one (hsa-miR-203a-5p) was also found to have significantly different expression levels between children with and without PPCS in a prior study.

“The value of our publication is that our findings come from multiple time points. We need more studies like this to continue to track how these microRNAs change over time and home in on those that are most consistent across patient populations,” says Dr. Miller, who is also research assistant professor of Pediatrics at Ohio State.

“Though there is a lot of research to be done still, salivary microRNAs show a lot of promise as becoming one of the first objective biomarkers clinicians may have access to help them with the diagnosis and management of concussion,” says Dr. MacDonald, who is also a professor in the Department of Pediatrics and Family Medicine at Ohio State.

The research was supported by Nationwide Children’s Intramural Funding Program awarded to Dr. MacDonald and Dr. Yang and by The Ohio State University’s Discovery Theme Initiative in Chronic Brain Injury.



Miller KE, MacDonald JP, Sullivan L, Rao Venkata LR, Shi J, Yeates KO, Chen S, Alshaikh E, Taylor HG, Hautmann A, Asa N, Cohen DM, Pommering TL, Mardis ER, Yang J, on behalf of the NCH Concussion Research Group. Salivary miRNA expression in children with persistent post-concussive symptoms. Frontiers in Public Health. 2022;10:890420.


Image credit: Adobe Stock

About the author

Lauren Dembeck, PhD, is a freelance science and medical writer based in New York City. She completed her BS in biology and BA in foreign languages at West Virginia University. Dr. Dembeck studied the genetic basis of natural variation in complex traits for her doctorate in genetics at North Carolina State University. She then conducted postdoctoral research on the formation and regulation of neuronal circuits at the Okinawa Institute of Science and Technology in Japan.