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Favorable Outcomes Possible With IVIG Treatment for Multisystem Inflammatory Syndrome in Children
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Further trials are required to examine the long-term feasibility of intravenous immunoglobulin (IVIG) for multisystem inflammatory syndrome.
Investigators found that favorable outcomes in children with multisystem inflammatory syndrome (MIS-C) can potentially be achieved with intravenous immunoglobulin (IVIG) monotherapy. However, the authors of the study published in the Egyptian Pediatric Association Gazette noted that supportive treatments such as vitamin D and C require further analysis to determine their efficacy.1
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Exhibiting similarities with Kawasaki disease, MIS-C began to emerge in April 2020, as the COVID-19 pandemic was in its early stages. The condition presents itself about 1 month following a COVID-19 infection and can result in cardiac complications in children who were previously healthy. Critically, a study showed that as more organ systems are impacted by MIS-C, factors such as mortality, length of hospital stay, and adverse medication events increase in likelihood of occurrence.1,2
An analysis of case studies involving MIS-C have found that children may present signs of acute neurological symptoms, and that immunomodulatory agents such as IVIG can provide a positive prognosis. Based on previous observations like these and the clinical features of MIS-C, the investigators sought to demonstrate the positive outcomes that can be obtained with IVIG monotherapy.3
The study was conducted during the early phase of the COVID-19 pandemic, from May 2020 to March 2021. In total, 95 patients who met multiple case definitions for MIS-C were included in the trial; SARS-CoV-2 antibody positivity was found in 94 patients (98.9%). Most patients (76.8%) had involvement of 4 or more organ systems, signifying potentially advanced disease.1,2
IVIG was administered at 2 g/kg in 77 patients (81%); due to sustained high inflammatory markers and unresponsiveness to the initial therapy, 66.3% of patients received an additional IVIG dose. Supplementally, all patients received vitamin D and C. Perhaps due to the high doses of IVIG, no steroids were necessary for any patient.1
In addition to IVIG, high-dose aspirin was administered to 81% of patients in the trial. Most of the patients (65.3%) continued anticoagulation with low-dose aspirin following the resolution of their fever. Six patients underwent plasmapheresis due to cardiac involvement or cerebral infarction due to MIS-C.1
The study authors determined that their findings suggest a positive impact in patients with MIS-C treated with a combination of IVIG and vitamin D and C supplementation. Importantly, this trial did not directly assess the outcomes of the children who were administered IVIG in the trial, and the investigators clarified that further research would be required to fully evaluate the outcomes of this and other immunomodulatory treatments.1
One unique sequence motif within the SARS-Cov-2 spike protein could be the key to IVIG’s potential effectiveness for MIS-C. According to the investigators, the motif shares similarities with bacterial superantigens, triggering a pathway leading to toxic shock syndrome that resembles Staphylococcal enterotoxin B. IVIG has been previously demonstrated to show a high affinity for Staphylococcal enterotoxin B. Its effectiveness for that treatment indication led the investigators to discuss IVIG’s potential as an effective therapy for MIS-C.1
IVIG displayed a particular benefit in patients with COVID-19-associated myocarditis, a serious heart condition; however, conflicting evidence exists supporting IVIG’s role in milder cases of MIS-C. Some case reports have demonstrated IVIG failures, with a large portion of patients requiring second doses. Importantly, no significant side effects were observed in patients who received a second dose in the current trial.1
Vitamins and their role in COVID-19 treatment have been thoroughly examined, with inconsistent results yielded. In the current study, 78% of patients had vitamin D levels below 20 ng/ml, with all patients receiving 2000 IU per day of vitamin D during their hospital stay. These preliminary data support the need for vitamin D supplementation in this patient population. However, regarding vitamin C, insufficient data supporting its use in COVID-19 was gathered.1
“Favorable outcomes may be obtained with IVIG monotherapy, while the effectiveness of supportive treatments like vitamin D and C requires further clinical investigation,” the study authors concluded.1
