Multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2: a systematic review
Abrams JY, Godfred-Cato SE, Oster ME, et al. J Pediatr. 2020;226:45-54.e1.
A new rare disease called the multisystem inflammatory syndrome in children (MIS-C) associated with pediatric SARS-CoV-2 infection has recently been reported. Early descriptions were inconsistent and based on a few children with this syndrome, which appears to be a postinfectious inflammatory reaction triggered by SARS-CoV-2 and to have some overlap with Kawasaki disease (KD). Probably most concerning is that MIS-C and KD both have frequent cardiac manifestations.
This study is a systematic review of published reports of MIS-C worldwide, aimed at describing the clinical and laboratory features of children diagnosed with MIS-C.
After a systematic review of the published literature, including Google searching, the authors identified 8 studies of children, involving a total of 440 participants.
All were cohort studies; there were no trials, and data all appear to have been retrospectively collected, although this is not stated directly. Several studies had cardiovascular involvement as an inclusion criterion for diagnosing MIS-C, thus probably distorting the true prevalence of cardiac involvement.
The results indicated that high-quality underlying data are lacking, and the condition appears to truly exist and to be distinct from KD.
The median patient age for MIS-C was approximately 7-10 years, whereas that for KD is usually 2-3 years. MIS-C spikes appeared to be temporally related to SARS-CoV-2 spikes in communities and typically occurred 4-6 weeks thereafter, or 4-6 weeks after the children’s COVID-19 symptoms.
In MIS-C, unlike KS, many children had GI symptoms (87%). Rash was common in both diseases (71% of MIS-C cases), and neurologic and cardiac symptoms were very common in MIS-C. Respiratory symptoms were relatively rare (30-40% of cases) in MIS-C.
Lab abnormalities were very common and often dramatic. The white-blood-cell counts averaged 15,000 cells/μL, with neutrophil predominance. Other inflammatory markers, such as erythrocyte sedimentation rate, C-reactive protein, ferritin, fibrinogen, and D-dimers, were almost always markedly elevated. Interestingly, platelets tended to be low, approximately 140,000 cells/μL, in MIS-C in contrast to KD. KD typically has markedly elevated platelet counts. Troponins were abnormal in approximately two-thirds of the MIS-C cases, whereas brain natriuretic peptide was elevated >90% of the time.
Most children tested negative for SARS-CoV-2 by PCR (only 25% positive), but 80-100% were antibody positive, thus again highlighting that this syndrome appears to occur in reaction to the infection and is not caused by the virus itself.
The treatments were generally intravenous immunoglobulin and steroids, along with general supportive care, although there is no evidence that these treatments result in better outcomes. Clinically, this entity will need to be considered in children with fever, particularly in areas with recent SARS-CoV-2 outbreaks, and in older children (7-10 years) who have a recent history of COVID-19-like symptoms with persistent illness.
EDITOR’S COMMENTARY: MIS-C is an apparently distinct postinfectious inflammatory condition triggered by SARS-CoV-2 infection. The syndrome appears to affect grade-school children several weeks after COVID-19 and is manifested by nonspecific symptoms, most commonly fever, GI symptoms, and rash. Cardiac complications occur, and although we have no high-quality evidence supporting a specific treatment strategy, the overlap between MIS-C and KD is driving treatment for this condition with intravenous immunoglobulin and steroids.
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