Children’s and Emory studies show evidence of COVID-19 and MIS-C biomarkers

Link to original article: Children's Healthcare of Atlanta | Sept. 27, 2021

Two inflammatory biomarkers, secretory phospholipase 2 and plasma osteopontin, were observed in patients with moderate to severe COVID-19 and multi-system inflammatory condition in children (MIS-C).

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). MIS-C often results in PICU admission, with complications including a weakening of the heart, cardiorespiratory failure, and even death. Currently, MIS-C is thought to be a post-infectious response to SARS-CoV-2. Moreover, it appears that MIS-C often affects previously healthy children who have no underlying comorbidities, resulting in a growing number of COVID-19-related PICU admissions. Being able to identify severe COVID-19 and MIS-C cases more quickly would help lead to improved patient care. 

Recently, the Children’s Healthcare of Atlanta and Emory University Pediatric Neurotrauma Lab and researchers from the Center for Childhood Infections and Vaccines and the Center for Clinical and Translational Research discovered multiple potential biomarkers for MIS-C. Both biomarkers, elevated levels of secretory phospholipase 2 and plasma osteopontin, are inflammatory biomarkers often identified in relation to Kawasaki disease or following traumatic brain injuries, respectively. Children's and Emory researchers discovered that these biomarkers were also elevated in COVID-19 positive and MIS-C patients. Findings from these studies were both published in the peer-reviewed journal, Experimental Biology and Medicine

The first study, published in July 2021 and funded by the Wilbur and Hilda Glenn Family Foundation, Michael and Natalie Beinenson, the Woodruff Health Sciences Center Synergy Award, and an Emory COVID-19 Cure award, led by Claudia Morris, MD, FAAP and Children's and Emory researchers to conclude that secretory phospholipase 2 may be a potential biomarker of COVID-19 severity and MIS-C in children. The second study, published in September 2021 and funded by the Elaine and John C. Carlos Chair Fund and a grant from the National Institutes of Health (NIH), led Dr. Reisner and his team to conclude that plasma osteopontin may also be a biomarker. While larger follow-up trials are needed to determine the specificity and predictability of this marker for widespread clinical use, these discoveries open the door to the development of new treatments for such patients, as well as the identification of an early biomarker of the severity of the disease. 

“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.”

A multi-disciplinary team from Children’s and Emory, including Dr. Reisner, Laura Blackwell, PhD, Stacy Heilman, PhD, and Iqbal Sayeed, PhD with the Pediatric Neurotrauma Lab, Dr. Morris in CCTR, as well as CCIV physicians Evan Anderson, MD, Andres Camacho-Gonzales, MD, MScAnn Chahroudi, MD, PhD, Preeti Jaggi, MDChristina Rostad, MD, Andi Shane, MD, and Jens Wrammert, PhD, led the way for this discoveries. The teams 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 secretory phospholipase 2 and plasma osteopontin biomarkers were significantly elevated in children with moderate and severe COVID-19 and MIS-C, compared to mild or asymptomatic children. Furthermore, both secretory phospholipase 2 and plasma osteopontin were uniquely correlated with clinical levels of severity in COVID-19 while other inflammatory markers were not.

“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.”