HMGB1 in Pediatric COVID-19 Infection and MIS-C: A Pilot Study

Abstract

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.

Keywords: COVID–19; HMGB1 (high mobility group box 1); MIS-C multisystem inflammatory syndrome in children; SARS–CoV2; infection - immunology.

Figure 1

(A) Western blot analysis of high-mobility group box 1 (HMGB1) expression in the serum of patients with the multisystem inflammatory syndrome in children (MIS-C), children with a recent history of COVID-19, healthy donors, and in two of the five children that performed a follow-up as indicated by square brackets. A representative blot for each group is shown. Patients with MIS-C (n = 5), children with recent history of COVID-19 (n = 2), healthy donors (n = 2), and follow up (n = 2). HMGB1 levels were detected by Western blot using rabbit anti-HMGB1 polyclonal Ab, and proteins were detected using ECL reagents. HMGB1 standard was included in the blot as an internal control. (B) Blot membrane was stained for total protein with Red ponceau, as a control for loading and transfer. The kDa indicates the approximate region of the blot where albumin would be expected.

Figure 2

High-mobility group box 1 levels were detected by Western blot in the sera of patients with MIS-C (n = 5), children with a recent history of COVID-19 (n = 20), healthy donors (n = 21), and in two of the five children that performed a follow-up. Densitometric values of HMGB1 levels are represented and summarized by Scatter plot analysis. Serum HMGB1 levels from both MIS-C children and pediatric subjects with a recent history of COVID-19 were compared to healthy donors. ****p < 0.0001.