Multisystem inflammatory syndrome in children is a SARS-CoV-2 triggered Kawasaki disease
Bibliographic record
Abstract
BACKGROUND: Multisystem Inflammatory Syndrome in Children (MIS-C) encompasses a spectrum of phenotypes: shock, Kawasaki disease (KD), and fever with hyperinflammation. Whether MIS-C is a new syndrome or SARS-CoV-2-triggered KD remains debated. To explore this, we investigated the relationship between clinical phenotypes and viral variants, and the contribution of pre-pandemic KD incidence to MIS-C reporting. METHODS: Single center, prospective, observational study of 384 patients with MIS-C, from March 2020 to September 2023. Clinical and laboratory features, complications, and outcomes were evaluated across the MIS-C waves. RESULTS: Three clinical phenotypes were identified: shock, KD, and fever with hyperinflammation. KD was most common across all variants, particularly during Omicron, while shock predominated in Delta cohort. Stratifying by phenotype outperformed the WHO MIS-C and RCPCH PIMS definitions in distinguishing subgroups. Countries with low pre-pandemic KD incidence identified MIS-C as a new syndrome, while countries with high KD incidence did not. CONCLUSIONS: MIS-C phenotypes vary accordingly to SARS-CoV-2 variants, with KD being most common. Stratification by clinical phenotypes out-performed MIS-C case definitions for patient identification, highlighting the value of clinical features in managing infection-triggered hyperinflammation. These findings, coupled with the inverse relationship between pre-pandemic KD incidence and MIS-C reporting, support the hypothesis that MIS-C is SARS-CoV-2-triggered KD. IMPACT: KD and MIS-C are not separate entities but different ends of the immune response spectrum. Among the hyperinflammation spectrum, each viral variant induces a distinct MIS-C phenotype, with the Omicron wave resembling KD. Clinical phenotype stratification outperformed MIS-C definitions in identifying patient subgroups, confirming the value of clinical features in managing infection-triggered hyperinflammation. The inverse relationship between pre-pandemic KD incidence and MIS-C reporting supports MIS-C being a SARS-CoV-2-triggered KD, underscoring critical equity and diversity considerations. A pathogen-agnostic approach to post-infectious hyperinflammation would recognize the full spectrum of phenotypes and complications and avoid confusion due to new naming conventions.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".