Doctors May Identify Which Kids' COVID-19 Cases are Severe Before Progressing

Sick girl in hospital bed

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Key Takeaways

  • A new study finds that certain protein levels in children can be a predictor of severe COVID-19 or MIS-C symptoms.
  • The findings may help doctors treat kids before their illness becomes severe.
  • The small study yields promising results, but more research is needed.

Sneezing and coughing are hallmarks of the fall season, especially in kids. With common colds, the flu, and COVID-19 running rampant, the return to in-person schooling has introduced an additional opportunity for germs to spread. Previously, there was no way to know if a child who is COVID-19 positive may endure severe symptoms. However, thanks to the scientists and doctors who have looked for ways to determine severity, a new study suggests we may have an indicator. 

The pilot study, published in the peer-reviewed journal Experimental Biology and Medicine in September 2021, found that increased blood levels of a specific protein—called plasma osteopontin (OPN)—were found in children with severe cases of COVID-19 and Multisystem Inflammatory Syndrome (MIS-C). Let's take a look at how these findings may help doctors treat kids before acute symptoms and hospitalizations occur.

Children who have recovered from MIS-C should make sure to stay on top of their COVID vaccinations. Research published in January 2023 showed patients with a history of MIS-C had no adverse reactions to the vaccine. One caveat—if your child has had MIS-C, they should wait 90 days after diagnosis to receive the vaccine.

What is OPN, and Why Is it Important?

Firstly, osteopontin is a protein found in human body fluids. Studies have shown that there is an increased amount in malignancies (abnormal cells that divide and spread throughout the body uncontrollably) and that it can stimulate some cancerous cells. Levels of plasma OPN have been linked to tumors and are also associated with significant injuries.

“We found that children with more severe injury to the brain have higher levels of osteopontin, potentially indicating more severe neurological disease and inflammation response to injury,” says Laura Blackwell, PhD, a senior neuropsychologist at Children’s Healthcare of Atlanta, and a co-author of the study.

Andrew Reisner, MD

This study demonstrates...that plasma osteopontin levels obtained on hospital admission are related to the clinical severity of COVID-19 in children.

— Andrew Reisner, MD

Dr. Blackwell notes that armed with this knowledge, researchers believe that children with severe COVID-19 symptoms and the neurological effects from MIS-C may also have elevated levels of the protein. The study at hand indicates that the ability to track the increased presence of OPN may help doctors know how serious a child’s COVID-19 illness will become, and what level of care may be needed.

“If a child is suspected of having COVID-19 and receives a positive test, then their blood can be tested at that point of care to evaluate their levels of plasma osteopontin immediately following the positive test,” says Andrew Reisner, MD, medical director of neurotrauma and a pediatric neurosurgeon at Children’s Healthcare of Atlanta. Dr. Reisner is the lead author of the study.

All About the Study

Researchers with Children’s Healthcare of Atlanta collected pediatric blood samples from 26 participants from March 17 to May 26, 2020. The randomly-selected kids ranged from newborn to 21 years old. They were grouped according to the level of their COVID-19 illness: mild or symptomatic, moderate, or severe.

Participants also included children diagnosed with MIS-C. Children who develop MIS-C have often had the virus that causes COVID-19, or have been exposed to others with the virus.

Researchers then analyzed the amount of plasma osteopontin in the blood samples and were able to equate the severity of the COVID-19 illness with the amount of OPN found.

“The severe COVID-19 and MIS-C groups had significantly higher levels of osteopontin at the time of collection compared to the other two groups,” explains Dr. Reisner. “This study demonstrates with statistical significance that plasma osteopontin levels obtained on hospital admission are related to the clinical severity of COVID-19 in children, with the highest levels noted in children with MIS-C.”

Experts note that OPN levels elevate as an inflammatory response to a fall, injury, or trauma. Since COVID-19 can cause inflammation, the heightened OPN levels could serve as a biomarker of COVID-19 and MIS-C in children. These markers can help medical professionals diagnose ailments, such as COVID-19, and/or their severity.

The results are striking, but with only 26 kids involved and no control group, it is a small study. The study also did not provide insight as to whether children with other severe diseases may also have this increased level of osteopontin. Despite those limitations, the initial findings are still hopeful.

“[The study] adds to an increasing body of work showing possible biomarkers for MIS-C that may help doctors recognize this condition early and treat patients before they become critically ill,” states Grant Schulert, MD, PhD, an assistant professor of pediatrics in the division of rheumatology at Cincinnati Children’s Hospital Medical Center.

Outlook For Future Care

The study authors acknowledge that larger sample sizes and longer testing time frames would strengthen the findings. The hope, however, is that this initial discovery could lead medical personnel on a path to more successful outcomes for children in the fight against COVID-19.

Laura Blackwell, PhD

Our study results show that children with more severe COVID-19 infection and symptoms...may be able to be identified earlier on with the support of this novel biomarker.

— Laura Blackwell, PhD

“Our study results show that children with more severe COVID-19 infection and symptoms and possibly with more complicated neurological disease may be able to be identified earlier on with the support of this novel biomarker, which could lead to earlier interventions and treatments,” Dr. Blackwell concludes.

What This Means For You

It's best to minimize your child's risk of contracting COVID-19 by ensuring that they are vaccinated, wear a face mask, wash their hands thoroughly, and practice social distancing. However, if your child does become infected, having their OPN levels tested as soon as they receive a positive COVID-19 diagnosis can help determine if their case may become severe. More research is needed, but the initial findings can help doctors better treat each child, or even prevent a downward spiral before it starts.


3 Sources
Verywell Family uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Reisner A, Blackwell LS, Sayeed I, et al. Osteopontin as a biomarker for COVID-19 severity and multisystem inflammatory syndrome in children: A pilot study. Exp Biol Med (Maywood). Published online September 26, 2021:15353702211046836. doi:10.1177%2F15353702211046835

  2. Elias MD, Truong DT, Oster ME, et al. Examination of adverse reactions after covid-19 vaccination among patients with a history of multisystem inflammatory syndrome in children. JAMA Netw Open. 2023;6(1):e2248987. doi:10.1001/jamanetworkopen.2022.48987

  3. Hao C, Cui Y, Owen S, Li W, Cheng S, Jiang WG. Human osteopontin: Potential clinical applications in cancer (Review). International Journal of Molecular Medicine. 2017;39(6). doi:10.3892/ijmm.2017.2964

By LaKeisha Fleming
LaKeisha Fleming is a prolific writer with over 20 years of experience writing for a variety of formats, from film and television scripts, to magazines articles and digital content. She has written for CNN, Tyler Perry Studios, Motherly, Atlanta Parent Magazine, Fayette Woman Magazine, and numerous others. She is passionate about parenting and family, as well as destigmatizing mental health issues. Her book, There Is No Heartbeat: From Miscarriage to Depression to Hope, is authentic, transparent, and providing hope to many.Visit her website at