ATLANTA (Sept. 27, 2021) – Previously there was no scientific evidence for a biomarker, a molecular indicator of disease severity enabling accurate treatment from onset, for COVID-19 positive children or multisystem inflammatory syndrome in children (MIS-C). Recently, the Children’s Healthcare of Atlanta Pediatric Neurotrauma Lab serendipitously discovered elevated levels of plasma osteopontin, an inflammatory biomarker they use to follow traumatic brain injuries (TBI) and concussions, were also elevated in COVID-19 positive and MIS-C patients. Findings from their initial pilot study were published today in the peer-reviewed journal, Experimental Biology and Medicine.
“As new scientific detail about COVID-19 emerged during the pandemic, the Pediatric Neurotrauma Lab at Children’s noticed similarities between our traumatic brain injury (TBI) biomarkers and what we are learning about COVID-19,” said Andrew Reisner, MD, Medical Director of Neurotrauma and Pediatric Neurosurgeon at Children’s. “We wanted to see if the biomarker we were studying for TBI could also identify those kids with COVID-19.”
Dr. Reisner, who also serves as the Elaine and John C. Carlos Chair for Neurotrauma at Emory University School of Medicine, led a multi-disciplinary team from Children’s and Emory, including Laura Blackwell, PhD, Stacy Heilman, PhD, Iqbal Sayeed with the Pediatric Neurotrauma Lab, and infectious diseases physicians Evan Anderson, MD, Andi Shane, MD and Christina Rostad, MD. The team reviewed residual blood samples of 26 children ages 0 to 21 years-old admitted to Children’s from March to May 2020. The patients were divided into a control group, mild or moderate COVID-19, severe COVID-19 and those who met U.S. Centers for Disease Control and Prevention’s (CDC) criteria for MIS-C. Levels of the plasma osteopontin biomarker were correlated with clinical data and were significantly elevated in children with moderate and severe COVID-19 and MIS-C, compared to mild or asymptomatic children. Furthermore, plasma osteopontin was uniquely correlated with clinical levels of severity in COVID-19 while other inflammatory markers were not.
Funded by the Elaine and John C. Carlos Chair Fund and a grant from the National Institutes of Health (NIH), the results led Dr. Reisner and his team to conclude that plasma osteopontin may be a biomarker of COVID-19 severity and MIS-C in children with potential future clinical uses. While larger follow-up trials are needed to determine the specificity and predictability of this marker for widespread clinical use, it is stable, easily accessible through a blood test, and can be quickly and affordably measured at the point of care.
“The osteopontin levels may potentially tell us the severity levels of COVID-19, maybe even before a patient deteriorates to the point that hospitalization and ventilator support are needed,” said Dr. Reisner. “We are hopeful that verification from follow up clinical trials will lead us there.”
Observed neurological similarities between TBI and COVID-19 included a primary event and secondary cascading events. For TBI the primary event may be a hard fall, while with COVID-19 it is entrance of the virus into the brain that leads to various inflammatory pathway activations in the brain. Both also cause injury to the nerves, glial cells and blood-brain barrier. The most striking similarities were inflammation, an immune response, and a cytokine (proteins that activate the immune system) storm. Coincidently, the Pediatric Neurotrauma Lab had been studying inflammatory and immune responses to trauma through an NIH grant years before the onset of the pandemic.