Plasma osteopontin may offer 'reliable biomarker' to predict COVID-19, MIS-C severity
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Plasma osteopontin levels are significantly higher in children hospitalized with moderate to severe COVID-19 and MIS-C than in those with mild or asymptomatic cases, suggesting a potential biomarker for disease severity, researchers said.
“There are currently no reliable biomarkers for COVID-19 or multisystem inflammatory syndrome, or MIS-C,” Andrew Reisner, MD, of Children’s Healthcare of Atlanta and the Emory University School of Medicine, told Healio Rheumatology. “A biomarker, like glucose levels or A1C in a diabetic patient, can help us predict the severity of a disease. Identifying if someone has a moderate or severe form of COVID-19 will help us inform the patient of what to expect over the course of their illness. Accordingly, we would know how to more accurately treat them.”
To examine plasma osteopontin as a potential biomarker for COVID-19 severity and MIS-C in children, Reisner and colleagues conducted a retrospective analysis of children and young adults who were admitted to Children’s Healthcare of Atlanta with COVID-19 between March 17 and May 26, 2020. The analysis included 26 patients aged 0-21 years. The researchers classified the patients into one of three categories based on COVID-19 severity: asymptomatic of minimally symptomatic, mild-to-moderate, and severe. Patients who were Asymptomatic of minimally symptomatic were made the control group.
In addition, the researchers established a fourth category for patients who met the CDC’s definition for MIS-C. They analyzed residual blood samples for osteopontin using commercial ELISA kits, with results correlated with clinical data.
According to the researchers, who published their findings in Experimental Biology and Medicine, plasma osteopontin levels significantly differed across the groups (P < .05). Osteopontin was “significantly elevated” in patients with moderate or severe COVID-19 and MIS-C, at a median of 430.32 ng/mL and 598.11 ng/mL, respectively, compared with those in the mild or asymptomatic groups.
In addition, osteopontin differentiated among levels of severity in COVID-19, while other inflammatory markers — including maximum erythrocyte sedimentation rate, C-reactive protein and ferritin, minimum lymphocyte and platelet counts, soluble interleukin-2R, and interleukin-6 — did not.
“The management of patients with SARS-CoV-2 infection would be facilitated with a reliable biomarker that is biologically stable, easily accessible, and can be rapidly and inexpensively measured at point of care,” Reisner said. “Osteopontin, a matricellular protein with diverse physiologic and pathologic functions in a variety of inflammatory and immune processes, has these features.”
“This study demonstrates that osteopontin is significantly upregulated in the plasma of hospitalized children with SARS-CoV-2 infection and MIS-C versus mild or asymptomatic children,” he added. “Further, osteopontin levels correlate with clinical severity of COVID-19, also with statistical significance. These new data suggest that osteopontin is a putative biomarker to guide risk stratification, prognostication, and clinical management of children with COVID-19 and MIS-C. The clinical utility of osteopontin as a COVID-19 biomarker requires validation in larger studies.”
Perspective
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While COVID-19 cases in children may not have reached the same level as the adult population, children have died from COVID-19 as well as MIS-C, a hyper-inflammatory response that can be seen in children following COVID-19 infection. As more data and research emerges surrounding COVID-19, as well as MIS-C, many clinicians are hopeful that this research will help shed light on patients who are at higher risk for severe disease, either COVID-19 or MIS-C.
This study evaluates the potential correlation between levels of osteopontin and severe COVID-19 and MIS-C in pediatric patients. While a small sample size, levels were noted to be increased with severe disease and even higher in children with MIS-C. More research is needed, but studies such as this could provide critical insight for providers caring for pediatric patients, identifying children at risk for severe disease and providing guidance for the best treatment to improve patient outcomes.
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