Multisystem inflammatory syndrome in children (MIS-C) is a rare but potentially severe post-infectious hyperinflammatory condition associated with SARS-CoV-2. It typically develops several weeks after infection and is characterized by fever, systemic inflammation, and variable involvement of the cardiovascular, gastrointestinal, mucocutaneous, hematologic, and other organ systems [1]-[3]. Although its phenotype overlaps with Kawasaki disease (KD), MIS-C more often affects older children and is more frequently accompanied by gastrointestinal symptoms, shock, myocardial dysfunction, and marked elevations of inflammatory and cardiac biomarkers [2]-[5].

Knowledge of MIS-C has evolved substantially since the first reports in 2020. The Council of State and Territorial Epidemiologists and the US Centers for Disease Control and Prevention (CSTE/CDC) introduced an updated surveillance case definition effective in 2023, emphasizing hospitalization, fever, C-reactive protein ≥ 30 mg/L, and new-onset involvement of at least two specified organ-system categories, together with laboratory or epidemiologic evidence of SARS-CoV-2 infection [6]. Importantly, this definition was designed for surveillance and does not replace clinical judgment [6].

More recent evidence also shows that the epidemiology of MIS-C has changed across SARS-CoV-2 variant and vaccination eras. The risk of MIS-C has been lower during Omicron-predominant periods than during earlier waves, and population-based data suggest declining incidence with increasing pediatric immunity and vaccination [7][8]. Nevertheless, MIS-C continued to occur during the large SARS-CoV-2 wave in China in late 2022 and early 2023. Chinese multicenter and single-center MIS-C series from this period have similarly described hyperinflammation, cardiovascular involvement, and KD-like features [9][10]. MIS-C was also documented among severe/critical pediatric COVID-19 cases during the late-2022 Omicron outbreak in Guangdong [11].

Because early Chinese data remain less abundant than data from Europe and North America, detailed description of cases from the early 2023 wave may help define the clinical spectrum in this setting. We therefore retrospectively summarized the clinical manifestations, laboratory findings, treatment patterns, and short-term outcomes of nine children with MIS-C treated at a tertiary pediatric emergency center in Guangzhou.

This case series describes nine children with MIS-C treated in Guangzhou during January-March 2023, immediately after the major SARS-CoV-2 wave in China. The principal phenotype was fever with prominent mucocutaneous inflammation, relative lymphopenia, markedly elevated inflammatory markers, and frequent cardiovascular involvement. Despite the small sample, this pattern is broadly consistent with contemporary evidence. A 2024 systematic review of 120 studies encompassing 20,881 MIS-C cases found fever to be nearly universal and reported gastrointestinal, dermatologic, inflammatory, coagulation, and cardiac abnormalities as central features of the syndrome [3]. A Chinese multicenter series of 64 children treated between December 2022 and June 2023 and a Beijing series of 11 children after Omicron infection similarly documented substantial systemic inflammation and cardiovascular involvement [9][10].

The cardiovascular signal in our cohort deserves emphasis. Four of nine children had coronary artery thickening/dilatation or ectasia, one had a coronary artery aneurysm, and cardiac biomarkers were substantially elevated at the cohort level. MIS-C can involve myocarditis-like ventricular dysfunction, shock, arrhythmia, and coronary abnormalities, and its cardiovascular phenotype partly overlaps with KD [2][4][5]. However, the two conditions are not interchangeable. Contemporary comparative studies and reviews indicate that MIS-C more often presents with shock, gastrointestinal involvement, myocardial dysfunction, lymphopenia, thrombocytopenia, and marked CRP, D-dimer, troponin, or natriuretic peptide elevation, whereas classic KD has a different age distribution and characteristic coronary vasculitis phenotype [2][4][5][12]. In the updated CSTE/CDC surveillance definition, a final diagnosis of KD by the treating team is considered an alternative diagnosis for surveillance classification, underscoring the need for careful phenotyping rather than labeling every KD-like illness after SARS-CoV-2 as MIS-C [6].

Our laboratory findings also align with the recognized hyperinflammatory phenotype. CRP, procalcitonin, fibrinogen, D-dimer, and IL-6 were elevated, while lymphocyte percentage and albumin were reduced. NT-proBNP and troponin were frequently elevated, supporting the importance of systematic cardiac assessment in suspected MIS-C. Notably, the median TNF-α concentration in this cohort was within the local reference interval; therefore, the data do not support describing TNF-α as uniformly elevated. Recent mechanistic work continues to distinguish MIS-C from severe acute pediatric COVID-19 at the immunologic and myeloid-response levels, reinforcing the concept that MIS-C is a post-infectious immune dysregulation syndrome rather than simply severe acute viral disease [13].

Treatment of MIS-C has evolved since the earliest pandemic period. In our cohort, all children received IVIG and aspirin, whereas only one received corticosteroids. This pattern should be interpreted in the historical and local context of early 2023 and should not be read as a current treatment recommendation. Contemporary reviews generally support IVIG and glucocorticoids as commonly used first-line immunomodulatory therapies, particularly in patients with cardiovascular involvement, although comparative observational studies have not been completely concordant [14]-[18]. A large international propensity-weighted cohort found no significant difference in major outcomes among IVIG alone, IVIG plus glucocorticoids, and glucocorticoids alone [15], while other cohorts have reported cardiovascular advantages with combination therapy [16]. More recent data also suggest that selected mild cases may respond to glucocorticoid-based strategies and that treatment should be individualized by severity and organ involvement [14][17]. Biologic agents are generally reserved for refractory or severe disease, but their optimal role remains uncertain [14].

The epidemiologic context has also changed. MIS-C became less frequent during Omicron-predominant periods, and population-level studies have documented declining incidence as immunity accumulated and pediatric vaccination expanded [7][8]. This is relevant to interpretation of our cohort: the nine cases were concentrated in a short interval following a major community SARS-CoV-2 wave, and the study was not designed to estimate incidence. The series therefore provides a clinical snapshot rather than evidence that MIS-C was common in the underlying pediatric population.

Several limitations should be acknowledged. First, this was a single-center retrospective case series of only nine patients, resulting in substantial imprecision and limiting generalizability. Second, there was no comparator group with KD, acute COVID-19, bacterial sepsis, or other inflammatory disorders, so the study cannot identify discriminative biomarkers or estimate diagnostic performance. Third, laboratory and imaging tests were obtained according to clinical need and were not measured at standardized time points, preventing analysis of biomarker trajectories. Fourth, treatment was not protocolized, and the study cannot compare the effectiveness of IVIG, glucocorticoids, aspirin, or other therapies. Fifth, only in-hospital outcomes were available; longer-term coronary and myocardial recovery cannot be assessed. Finally, because the cohort was assembled during a period when MIS-C definitions were evolving, future studies should prospectively apply a single prespecified case definition and explicitly report the timing and modality of SARS-CoV-2 evidence.

In conclusion, children with MIS-C in this early-2023 Guangzhou case series most often presented with fever, KD-like mucocutaneous inflammation, marked systemic inflammation, and cardiovascular involvement. All patients survived to discharge, but the small sample precludes conclusions about prognosis or treatment effectiveness. Multicenter prospective studies using standardized diagnostic phenotyping, serial cardiac assessment, and longer follow-up are needed to define the contemporary MIS-C phenotype in China and to distinguish it reliably from KD, acute COVID-19, and other hyperinflammatory conditions.

The study protocol was approved by the Clinical Research Ethics Committee of Guangzhou Women and Children’s Medical Center (approval No. 432A01). The requirement for informed consent was waived because of the retrospective observational design.

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

This case series characterizes MIS-C in Chinese children during the early-2023 period following a major community SARS-CoV-2 wave.MIS-C showed a prominent Kawasaki disease-like mucocutaneous phenotype accompanied by frequent cardiovascular involvement.Hyperinflammation, coagulation activation, relative lymphopenia, hypoalbuminemia, and elevated cardiac biomarkers constituted the major laboratory phenotype.All children received IVIG and aspirin, while only one received corticosteroids; all survived to hospital discharge.These findings provide a clinically detailed snapshot of MIS-C in China during a rapidly changing post-Omicron epidemiologic era.

Yining Sun: data curation, formal analysis, and writing—original draft. Li Huang: Study design, manuscript review. Zihao Tan: conceptualization, supervision, and writing—review and editing.