Combination of Corticosteroids and IVIG Appear Effective in the Treatment of Children With MIS-C

Combining the corticosteroid methylprednisolone with intravenous immunoglobulin (IVIG) was shown to improve course of fever in patients with multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 infection, according to a study published in JAMA.

Although children only account for between 1% and 2% of hospitalized patients with COVID-19, severe systemic hyperinflammatory disease was reported in children in Europe and the United States, occurring 2 to 4 weeks after SARS-CoV-2 infection. The novel condition, MIS-C, presents a range of clinical features, including persistent fever, digestive symptoms, rash, bilateral nonpurulent conjunctivitis, mucocutaneous inflammation signs, and frequent cardiovascular involvement. Further, the condition is often associated with hemodynamic failure, with acute cardiac dysfunction requiring hemodynamic support in 60% to 75% of cases, and it is sometimes associated with death.

MIS-C is the most severe pediatric disease associated with SARS-CoV-2 infection, and according to the authors of the study, the optimal therapeutic strategy for this potentially life-threatening condition is currently unknown. The investigators examined 106 reported cases of suspected MIS-C that fit the WHO definition of the condition, and who received either IVIG alone or a combination of IVIG and methylprednisolone. The goal was to analyze and compare treatment failure percentage between the 2 treatment arms, with failure defined as a persistence of fever 2 days after starting the treatment or recurrence of fever 7 days after treatment.

Among the 106 patients assessed, 34 received the combination treatment while 72 received IVIG alone. None received any other immunomodulatory treatment before the initial therapy, and the dosage of IVIG was 2 g/kg for all patients. Patients who received the combination therapy tended to have a more severe initial presentation.

According to the study authors, 9% of the children receiving the combination therapy did not respond to treatment, compared to 51% of children receiving IVIG alone. Treatment with IVIG and methylprednisolone vs IVIG alone was associated with a more favorable fever course and less severe acute complications, including acute left ventricular dysfunction and hemodynamic support requirement. The investigators concluded that the apparent efficacy of corticosteroids in the treatment of MIS-C could be similar to their usefulness in the treatment of acute respiratory distress syndrome related to SARS-CoV-2 infection in adults.

The researchers mention a number of limitations to the current study, including a lack of randomization, the lack of complete certainty that all patients observed had MIS-C, and the variation in dosage in the combination arm. They also warn that patients with initial MIS-C may show symptoms of septic shock, and initial treatment with IVIG and methylprednisolone has a theoretical risk of worsening an unrecognized bacterial infection. Finally, the investigators said that additional studies are warranted to understand the mechanisms underlying this possible corticosteroid effect in MIS-C and in severe forms of COVID-19.

REFERENCE

Ouldali N, Toubiana J, Antona D, et al. Association of intravenous immunoglobulins plus methylprednisolone vs immunoglobulins alone with course of fever in multisystem inflammatory syndrome in children. JAMA. 2021;325(9):855-864. doi:10.1001/jama.2021.0694