New immune biomarkers could help predict the requirement for ICU admission in children developing systemic inflammatory syndrome after COVID-19

Although most children recover from COVID-19 with no or mild symptoms, in rare cases, weeks after the infection, their immune system reacts disproportionately and causes multisystem inflammatory syndrome (MIS-C). This rare but serious disease can affect the heart, lungs, or digestive system and, in some cases, requires ICU admission.

A new study published in Pediatric Research has now identified blood soluble biomarkers that could anticipate which patients are at higher risk of developing more severe outcome, allowing for rapid intervention and evidence-based clinical decision-making. The work was led by the IrsiCaixa team –a center jointly supported by the “la Caixa” Foundation and the Department of Health of the Generalitat of Catalonia– and included collaboration with the Hospital Sant Joan de Déu and the Barcelona Institute for Global Health (ISGlobal).

MIS-C is a severe inflammatory disorder that usually appears two to six weeks after a SARS-CoV-2 infection. In Catalonia, between 2020 and 2022, 152 cases were recorded, most of them in children aged 4 to 11. Although it is rare –and even more so since the arrival of the Omicron variant– when it occurs, it can be life-threatening.

Six markers that predict severity

By measuring 92 inflammatory molecules in the serum of 22 pediatric patients who had experienced MIS-C, the study identified six markers –IL-2, IL-33, CD244, SCF, TNFRSF9 (soluble), and CD8α (soluble)– that can predict with good accuracy which patients will require ICU admission. In particular, lower levels of CD244 and TNFRSF9 were associated with longer hospital stays. “These markers form an ‘immune signature’ capable of distinguishing between more and less severe cases,” says Tetyana Pidkova, a predoctoral researcher at IrsiCaixa and the study’s first author.

Additionally, the researchers compared the immune markers of children with MIS-C at diagnosis with those of children who had recovered from COVID-19 weeks earlier. The study identified 29 altered biomarkers, including cytokines, chemokines, and immune regulators. This finding helps to better understand which immune system processes are specifically involved in MIS-C. “What we observed is that in this disease, the immune ‘alarm system’ is triggered uncontrollably, causing widespread inflammation that can damage multiple organs. Identifying the specific biomarker signature associated with MIS-C will help decipher the immune disregulation responsible for the disease,” emphasizes Benjamin Trinité, an associate researcher at IrsiCaixa.

Patient follow-up showed that all altered markers returned to normal within two months of starting treatment, confirming that current anti-inflammatory therapies are effective and that the immune response does not leave significant medium-term sequelae.

Anticipating risk and better understanding MIS-C

Having specific immune markers opens the door to early identification of patients who are more likely to develop a severe condition, allowing medical interventions to be prioritized before complications arise. “The study provides us with a precise and validated molecular basis to guide clinical practice,” explains Julià Blanco, principal investigator at IrsiCaixa and IGTP. “At the same time, it helps us better understand how MIS-C works, a disorder we still know little about, but which remains one of the biggest challenges COVID-19 has left in pediatric care.”