Pangonis

Editor's Notes

• #6: Most children & adolescence have mild disease or are asymptomatic
• #8: ↑ MIS-C cases noted ~4 weeks after COVID cases increased
• #9: Initial case definition by RCPCH – identified as a unique entity
• #10: Different case definitions exist – UK (RCPCH), WHO & CDC – problematic for multi-country studies Main Differences Age Duration of fever Some specify symptoms
• #11: Initially, most cases were in non-Hispanic AA & Hispanic/Latino patients. This gap between them and Caucasians has been closing in the past few months
• #12: Symptoms vary by age MMWR report (455 cases) – 90% had GI symptoms, 100% had fever
• #13: Oral ulceration & vesicular rash are suggestive of an alternate diagnosis Pulm included pulmonary edema, infiltrates on imaging. May be difficult to separate CV from Pulmonary Most common systems – GI & CV Less common – Cervical LAD
• #14: Data from NY Matches worldwide data
• #15: Fig. 1 | Pathogenesis of multisystem inflammatory syndrome in children: a hypothesis. The timing of the interferon (IFN) response to SARS-CoV-2 infection can vary with viral load and genetic differences in host response. When viral load is low, IFN responses are engaged and contribute to viral clearance, resulting in mild infection. When viral load is high and/or genetic factors slow antiviral responses, virus replication can delay the IFN response and cytokine storm can result before adaptive responses clear the virus, resulting in severe disease including multisystem inflammatory syndrome in children (MIS-C). Adapted with permission from REF. 9, Elsevier.
• #16: Neutrophil-rich inflammation Evidence of complement activation
• #17: Low T- & B-cells Circulating lymphocyte subsets may not reflect [tissue] Anti-Endoglin found in KD & MIS-C patients Autoantibodies identified Causative or result of damage?
• #18: LCA 1 & 3: 60-70% IgG+ PCR- : Latent Class Analysis  Good for grouping syndromes/disorders by unique features. MIS-C cases reported to the CDC were stratified into 3 categories based on similarities & overlapping features with acute COVID and/or KD Based on this analysis, we conclude that Class 1 cases represent true MIS-C, and that many children with acute respiratory COVID-19 and with Kawasaki disease, two conditions that are distinct from MIS-C, were unintentionally included among reported cases because the CDC criteria are overly broad.
• #19: ½ way point CAAs in KD vs. MIS-C (25-60% vs. 18%) CAAs in KD more likely to be permanent & lead to complications  Rupture, MI & Death KD had higher levels of IL-17A ↑ plasma biomarkers of arterial damage in KD vs. MIS-C ↑ autoantibodies to EDIL3  glycoprotein in arterial walls regulated by response to vascular injury  inhibits inflam cell recruitment & extravasation across endothelium
• #20: CAAs in KD vs. MIS-C (25-60% vs. 18%). Aneurysms reported with MISC but rare CAAs in KD more likely to be permanent & lead to complications  Rupture, MI & Death KD had higher levels of IL-17A ↑ plasma biomarkers of arterial damage in KD vs. MIS-C ↑ autoantibodies to EDIL3  glycoprotein in arterial walls regulated by response to vascular injury  inhibits inflam cell recruitment & extravasation across endothelium
• #21: Clinical judgement can supersede criteria if suspicion is strong enough
• #22: + + = mostly class 1 & 3 ANY TEST POSITIVE = 565 / 570 EPI LINK ONLY (NO TESTS DONE) = 5 / 570
• #23: Some institutions give a 2nd dose of IVIG. No data to support this.
• #24: Shorter half-life Shorter duration of neutropenia/leukopenia Toci: Fully humanized monoclonal antibody Data obtained from the package inserts for anakinra and tocilizumab.
• #26: Looking for predictors – mild (non-severe) vs. severe Age & Race entered into model a priori Other variables added if significant from analysis. Backwards elimination model In Cohort studies: The proportion of exposed with disease development compared to proportion of unexposed with disease development
• #28: Heme & resp removed
• #29: Lab criteria met?
• #30: Mild or Severe?
• #37: Cases with similar presentations prior to COVID pandemic may have been labeled as an autoinflammatory syndrome NOS or MAS/HLH Comparing this to KD – clinicians still debate over who fits diagnostic criteria and who should be treated out of caution.
• #39: PRISM study: immunology & long term outcome study Prevail looking for genetic markers of susceptibility
• #42: The supplementary criteria include: ALC < 1000/uL if older than 8 months (< 4500 if age < 8 mo) Platelet count < 150,000/µL Na < 135 mmol/L Neutrophilia (Elevated Absolute neutrophil count) Albumin < 3 g/dl D is the correct answer Total WBC count is not included as a supplementary criteria
• #43: Shock/hypotension Cardiac dysrhythmias ↑ Troponin T Need for invasive or non-invasive respiratory support Concern for rapid progression
• #44: Abdominal pain & GI symptoms are the most common symptoms reported (other than fever which is absolutely required). However, since vomiting has already been counted would not include abd pain. Headache is included as a neurological symptom and is the correct answer Tachycardia is too broad by itself as it can be caused by agitation, fever, etc… Unexplained tachycardia is shock until proven otherwise, so it makes sense to only include shock as a clinical criteria Vesicular rashes & oral ulcerations are more suggestive of viral infections. These are considered exclusion criteria for Kawasaki Disease and thus also considered so for MIS-C