Osteopontin Biomarker Evaluated for COVID-19 Severity and MIS-C

Multisystem inflammatory syndrome in children (MIS-C) is a serious condition that appears to be linked to coronavirus disease 2019 (COVID-19). Most children who become infected with the COVID-19 virus have only a mild illness.

Osteopontin (OPN) is a highly phosphorylated glycophosphoprotein having acidic characteristics and rich in aspartic acid. OPN, a multifunctional protein, has important functions on cardiovascular diseases, cancer, diabetes and kidney stone diseases and in the process of inflammation, biomineralization, cell viability and wound healing.


Pediatricians at the Emory University School of Medicine (Atlanta, GA, USA) and their colleagues evaluated the candidacy of plasma osteopontin (OPN) as a biomarker of COVID-19 severity and multisystem inflammatory condition in children (MIS-C) in children. They conducted a retrospective analysis of 26 children (0–21 years of age) admitted to Children’s Healthcare of Atlanta (Atlanta, GA, USA) with a diagnosis of COVID-19 between March 17 and May 26, 2020.

The patients were classified into three categories based on COVID-19 severity levels: asymptomatic or minimally symptomatic (control population, admitted for other non-COVID-19 conditions), mild/moderate, and severe COVID-19. A fourth category of children met the Centers for Disease Control and Prevention's case definition for MIS-C. Residual blood samples were analyzed for OPN, a marker of inflammation using commercial ELISA kits (R&D Systems, Minneapolis, MN, USA), and results were correlated with clinical data.

The investigators reported that plasma osteopontin levels significantly differed across the groups. 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.

Andrew Reisner, MD, a Neurosurgeon and first author of the study, said, “This study demonstrated that osteopontin is significantly upregulated in the plasma of hospitalized children with SARS-CoV-2 infection and MIS-C versus mild or asymptomatic children. Further, osteopontin levels correlated 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 authors concluded that OPN is a potential biomarker of COVID-19 severity and MIS-C in children that may have future clinical utility. The specificity and positive predictive value of this marker for COVID-19 and MIS-C are areas for future larger prospective studies. The study was published on September 26, 2021 in the journal Experimental Biology and Medicine.

Related Links:
Emory University School of Medicine
Children’s Healthcare of Atlanta
R&D Systems