Multisystem inflammatory syndrome in children (MIS-C) and “Near MIS-C”: A continuum?

Abstract

IntroductionReports of multisystem inflammatory syndrome in children (MIS-C), following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, have been increasing worldwide, with an incidence varying significantly across studies based on the definition used for the diagnosis. At our tertiary medical center in Lebanon, we encountered several cases that presented a diagnostic challenge because they mimicked MIS-C but did not meet the US Centers for Disease Control and Prevention (CDC) definition. We decided to review these cases and describe their features in comparison with cases that met the CDC criteria of MIS-C and those that had an alternative diagnosis.MethodsThis is a retrospective chart review of subjects aged <19 years old admitted to the American University of Beirut Medical Center (AUBMC) between March 1, 2020, and May 31, 2021, with suspected or confirmed MIS-C, following documented COVID-19 infection, with sufficient or insufficient criteria for diagnosis. Subjects were classified into 3 groups: “MIS-C”, “Near MIS-C” and “Alternative Diagnosis”.ResultsA total number of 29 subjects were included in our cohort. Fever was present in all subjects. In the MIS-C group, evidence for cardiovascular system involvement was the most common feature followed by the mucocutaneous and gastrointestinal systems. In the “Near MIS-C” and “Alternative Diagnosis” group, gastrointestinal symptoms were the most common with only one patient with cardiac abnormalities and none with coagulopathy. Subjects with typical MIS-C presentation had higher inflammatory markers when compared to subjects in the other groups. Almost all the subjects had positive IgG for SARS-CoV-2. Of the 29 subjects, the Royal College of Paediatrics and Child Health (RCPCH) case definition would have identified all suspected cases without an alternative diagnosis as MIS-C, whereas the World Health Organization (WHO) and the CDC definitions would have excluded 6 and 10 subjects, respectively.ConclusionMIS-C presents a diagnostic challenge due to the nonspecific symptoms, lack of pathognomonic findings, and potentially fatal complications. More research is needed to fully understand its pathogenesis, clinical presentation spectrum, and diagnostic criteria. Based on our experience, we favor the hypothesis that MIS-C has a continuum of severity that necessitates revisiting and unifying the current definitions.

Vitamin D Supplementation in Neonatal and Infant MIS-C Following COVID-19 Infection

“…Since April 2020, reports of children presenting with severe hyperinflammatory manifestations after COVID-19, resulting in a critical illness requiring hospitalization, started to appear. This acute condition, generally developing 3-6 weeks after SARS-CoV-2 infection, has been defined as "pediatric multisystem inflammatory syndrome temporally associated with COVID-19" (PIMS-TS) by the Royal College of Pediatrics and Child Health (RCPCH) in UK and "multisystem inflammatory syndrome in children" (MIS-C) by the World Health Organization (WHO) and by the US Centers for Disease Control and Prevention (CDC) [8,[19][20][21].…”

“…To date, there is mounting evidence that a small minority of children infected with SARS-CoV-2 later develop MIS-C, especially in those regions where the COVID-19 burden was higher [16,19,21,22]. According to the CDC diagnostic criteria, MIS-C patients are younger than 21 years, present with fever and laboratory evidence of multisystem involvement (two or more domains involved), and need hospitalization in the absence of an alternative diagnosis.…”

“…Despite the symptoms overlapping mainly with Kawasaki disease, there are some epidemiologic differences, helping clinicians in differentiating between the two conditions. A summary of the currently available diagnostic criteria for MIS-C [19,24,25,35] and KD [36][37][38][39] is shown in Table 1. Moreover, it should be noted that the available evidence accounts for an older age of MIS-C patients compared to KD (median 7-11 years vs. < 5 years of age), and for a higher prevalence of the disease in children of Hispanic and African ancestry compared to the well-known predominance of Kawasaki disease in children of Asian descent.…”

“…A key role in this context is played by vitamins (i.e., vitamin A, vitamin C, and vitamin D) and oligoelements (i.e., zinc, selenium), which deficiency has been shown to affect, to a various extent, immune functions. Moreover, also dietary supplements, such prebiotics and probiotics, are known to be important in supporting immune defenses, as they directly affect microbiota composition and functions [19,47,50,53,54,56,[59][60][61].…”

Manifestaciones cardíacas y hallazgos ecocardiográficos asociados al síndrome inflamatorio multisistémico por COVID-19 en niños

“…The RT-PCR test can accurately detect the virus even at lower concentrations, which is crucial for identifying cases where the infection has passed the acute phase but could still contribute to developing complications such as MIS-C [20]. This differentiated diagnostic approach is vital for ensuring accurate detection of COVID-19 infection and, therefore, for appropriate management and early intervention in patients with MIS-C. Pediatrics [21].…”