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Published on: December 10, 2013
HMGB1 in Pediatric COVID-19 Infection and MIS-C: A Pilot Study
Laura Petrarca1,2, Valeria Manganelli3, Raffaella Nenna1
1Maternal Infantile and Urological Sciences Department, Sapienza University of Rome, Rome, Italy.
Insights
High-mobility group box 1 (HMGB1) serum levels were significantly elevated in children with multisystem inflammatory syndrome (MIS-C) compared to COVID-19 survivors and healthy children. This suggests HMGB1 may be a potential biomarker for severe illness in MIS-C.
Area of Science:
- Pediatrics
- Immunology
- Infectious Diseases
Background:
- The coronavirus disease 2019 (COVID-19) pandemic has led to the emergence of multisystem inflammatory syndrome in children (MIS-C), a novel condition in previously healthy children.
- High-mobility group box 1 (HMGB1), a pro-inflammatory molecule, is hypothesized to play a role in the pathogenesis and clinical presentation of MIS-C.
Purpose of the Study:
- To describe the clinical characteristics of MIS-C patients.
- To compare serum levels of HMGB1 in MIS-C patients with those of children with a history of SARS-CoV-2 infection and healthy controls.
Main Methods:
- Serum HMGB1 levels were determined using Western blot in 46 children.
- Participants were categorized into three groups: five MIS-C patients, 20 children with a history of SARS-CoV-2 infection, and 21 healthy children (controls).
Main Results:
- Median HMGB1 serum levels were significantly higher in MIS-C patients compared to both COVID-19 survivors (1,151.38 vs. 545.90 DU, p=0.001) and controls (1,151.38 vs. 320.33 DU, p=0.001).
- HMGB1 levels in MIS-C patients with coronary involvement were slightly higher than in those without coronary dilatation (1,225.36 vs. 1,030.49 DU, p=0.248).
- Follow-up HMGB1 levels in two MIS-C patients decreased to levels comparable to the control group.
Conclusions:
- The elevated HMGB1 protein levels in the serum of MIS-C and COVID-19 patients indicate its involvement in inflammatory processes.
- HMGB1 may serve as a potential biomarker and therapeutic target for severe illness in MIS-C patients.
Objective:
Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, a novel syndrome known as a multisystem inflammatory syndrome in children (MIS-C) was reported in previously healthy children. A possible pro-inflammatory molecule, high-mobility group box 1 (HMGB1), may be assumed to play an important role in the pathogenesis and clinical presentation of MIS-C. We described the clinical picture of patients with MIS-C and we also aimed to test and compare HMGB1 serum levels of MIS-C patients with those of patients with previous SARS-CoV2 infection and healthy children.
Study Design:
We determined HMGB1 levels by Western blot in 46 patients and divided them into three groups, namely, five patients with MIS-C (median age: 8.36 years), 20 children with a history of SARS-CoV-2 infection (median age: 10.45 years), and 21 healthy children (controls) (median age: 4.84 years), without evidence of respiratory infection in the last 3 months.
Results:
The median level of HMGB1 in the serum of five patients with MIS-C was found to be significantly higher compared with both patients with a recent history of COVID-19 (1,151.38 vs. 545.90 densitometric units (DU), p = 0.001) and control (1,151.38 vs. 320.33 DU, p = 0.001) groups. The HMGB1 level in MIS-C patients with coronary involvement had a slightly higher value with respect to patients without coronary dilatation (1,225.36 vs. 1,030.49 DU, p = 0.248). In two of the five children with MIS-C that performed a follow-up, the HMGB1 value decreased to levels that were superimposable to the ones of the control group.
Conclusion:
The significantly high level of HMGB1 protein found in the serum of COVID-19 and patients with MIS-C supports its involvement in inflammatory manifestations, suggesting HMGB1 as a potential biomarker and therapeutic target in patients with severe illness.

