01Approach to the Critical Patient/attcp51

Immediate stabilization

›Airway and breathing

›Respiratory failure indication for escalation

›SpO2 < 92% on room air

›Increased work of breathing with accessory muscle use

›Tachypnea > 40/min in child < 1 year or > 30/min in older child

›Supplemental oxygen titrated to SpO2 >= 94%

›High-flow nasal cannula if standard oxygen inadequate

›Non-invasive ventilation for progressive hypoxemia

›If respiratory failure or altered mental status, prepare for intubation

›RSI with ketamine preferred to avoid cardiovascular depression

›Avoid etomidate in setting of possible adrenal insufficiency

›Circulation and shock management

›Hemodynamic instability features

›HR > 130 in child > 5 years or > 150 in child < 5 years

›SBP < 70 + (2 x age in years) mmHg in child < 10 years

›Capillary refill > 3 seconds or mottled skin

›IV/IO access and fluid resuscitation

›10 mL/kg isotonic crystalloid bolus, repeat to 20–40 mL/kg with reassessment

›Caution with aggressive fluid loading if myocardial dysfunction present

›If no improvement after 20 mL/kg, initiate vasoactive support

›Vasoactive agents required in up to 50–73% of cases

›Norepinephrine 0.05–0.5 mcg/kg/min for vasodilatory shock

›Milrinone 0.25–0.75 mcg/kg/min for cardiogenic component

›Epinephrine 0.05–0.3 mcg/kg/min for refractory shock

Monitoring and targets

›Continuous monitoring bundle

›Cardiac monitoring with continuous ECG

02History/hx63

Cardinal symptoms

›Fever characteristics

›Persistent fever >= 38.0 C for > 24 hours (CDC) or >= 3 days (WHO)

›Universal feature, present in 99% of confirmed cases

›Fever duration 3–7 days typical at presentation

›Timing relative to SARS-CoV-2

›Onset 2–8 weeks after known or suspected COVID-19 infection

›Many had asymptomatic or mild initial SARS-CoV-2 infection

›Gastrointestinal symptoms

›Abdominal pain present in 70–87% of cases

›Severe pain may mimic appendicitis or intussusception

›Mesenteric lymphadenitis and bowel wall thickening on imaging

›Vomiting and diarrhea common

›May precede fever by 1–2 days in some cases

›Persistent vomiting contributes to dehydration and hemodynamic compromise

›Mucocutaneous features

›Rash present in 59% of cases

›Diffuse maculopapular or erythematous distribution

›Less prominent than classic Kawasaki disease

›Conjunctival injection in 57%

›Bilateral and nonpurulent

›Oral mucosal changes in 42%

›Cracked or erythematous lips

›Strawberry tongue

›Cardiovascular symptoms

›Chest pain and palpitations

›Suggests myocardial involvement

›Exercise intolerance or syncope with exertion

03Physical Exam/exam49

Vital signs and general assessment

›Hemodynamic snapshot

›Temperature: fever universal (>= 38.0 C)

›Hypothermia a sign of septic shock

›Heart rate: tachycardia out of proportion to fever

›HR > 130/min in older children suggests shock physiology

›Blood pressure: hypotension in up to 50% at presentation

›Use age-appropriate norms for pediatric hypotension thresholds

›Respiratory rate: tachypnea in 30% requiring ventilatory support

›Perfusion status

›Capillary refill time

›> 3 seconds indicates poor perfusion

›Skin color and temperature

›Mottling, pallor, or peripheral cyanosis

›Cold extremities vs warm extremities suggests different shock physiology

Cardiovascular exam

›Cardiac auscultation

›Gallop rhythm (S3) suggests myocardial dysfunction

›Present in subset with significant LV dysfunction

›Muffled heart sounds suggesting pericardial effusion

›Effusion present in approximately 23% of cases

›Arrhythmias or irregular rhythm

›AV block in up to 20% including progression to 2nd and 3rd degree

›Peripheral perfusion signs

›Jugular venous distension in older children with fluid overload

›Hepatomegaly from venous congestion or hepatitis

›Hypoalbuminemia contributes to ascites and peripheral edema

04Differential Diagnosis/ddx43

Life-threatening mimics

›Bacterial sepsis

›ICD-10 A41.9 — sepsis, unspecified organism

›Positive blood cultures distinguish from MIS-C

›MIS-C cultures sterile despite severe inflammation

›Focal source of infection identifiable in bacterial sepsis

›Pneumonia, urinary tract infection, meningitis

›Toxic shock syndrome

›Staphylococcal TSS: ICD-10 A48.3

›Toxin-producing Staphylococcus aureus identified

›Desquamation typically later than rash in MIS-C

›Streptococcal TSS: ICD-10 A48.3

›Group A Streptococcus identified on culture

›Kawasaki disease

›ICD-10 M30.3 — Kawasaki disease

›Age typically < 5 years vs MIS-C median 8–9 years

›Higher platelet count and lower CRP than MIS-C

›Coronary artery aneurysms more common in KD

›Less shock and LV dysfunction than MIS-C

›Macrophage activation syndrome / HLH

›ICD-10 D76.1 — hemophagocytic lymphohistiocytosis

›Markedly elevated ferritin (often > 10,000 mcg/L)

›Pancytopenia, splenomegaly, hemophagocytosis on bone marrow biopsy

›Can coexist with MIS-C

Cardiac mimics

›Viral myocarditis

›ICD-10 I40.0 — infective myocarditis

›Isolated cardiac involvement without multisystem inflammation

05Laboratory Tests/lt66

Inflammatory markers

›C-reactive protein

›Markedly elevated in MIS-C — median approximately 22 mg/dL (220 mg/L)

›Significantly higher than Kawasaki disease (median 6.7 mg/dL)

›Serial trending every 24–48 hours to assess treatment response

›Erythrocyte sedimentation rate

›Elevated but less discriminating than CRP

›Useful for trend monitoring

›Ferritin

›Often 500–2,000 mcg/L in MIS-C

›Values > 10,000 mcg/L suggest MAS/HLH overlap

›Markedly elevated ferritin triggers MAS scoring

›Procalcitonin

›Elevated but nonspecific

›Helps support hyperinflammatory state but does not confirm bacterial sepsis

Hematology and coagulation

›Complete blood count with differential

›Lymphopenia in majority

›Neutrophilia common

›Thrombocytopenia in 30–40% (< 150 x10^9/L)

›Anemia (mild to moderate, normocytic)

›Thrombocytosis may occur later in disease course

›Paradoxical finding compared to KD which shows thrombocytosis acutely

›Coagulation panel

›D-dimer markedly elevated — median approximately 3,578 ng/mL

›Guides anticoagulation decision-making

›Serial monitoring during hospitalization

›Fibrinogen

06Diagnostic Tests/dt74

Scoring Systems

›CDC case definition for MIS-C

›Criteria required (all must be met)

›Age < 21 years

›Fever >= 38.0 C for >= 24 hours

›Laboratory evidence of inflammation (CRP, ESR, fibrinogen, procalcitonin, D-dimer, ferritin, LDH, IL-6 elevated)

›Multisystem involvement (>= 2 organ systems)

›SARS-CoV-2 PCR positive, serology positive, or antigen positive, or COVID-19 exposure within 4 weeks prior

›No alternative plausible diagnosis

›Sensitivity and specificity comparable to WHO and RCPCH definitions

›WHO case definition

›Additional criterion: fever >= 3 days

›Requires exclusion of other microbial causes

›Validated distinguishing scores

›Scoring tools distinguish MIS-C from COVID-19, Kawasaki disease, and TSS

›AUC 0.87–0.97 in validation cohorts

›Based on age, CRP/platelet ratio, lymphocyte count, BNP, troponin

›MAS/HLH screening — HScore

›Ferritin > 10,000 mcg/L triggers full HLH evaluation

›Bone marrow biopsy for hemophagocytosis

›HScore > 169 yields 93% probability of HLH

MRI

›Cardiac MRI indications

›Indicated 2–6 months post-acute illness if initial LVEF < 50%

›Evaluates myocardial fibrosis and scarring (late gadolinium enhancement)

›Assesses persistent subclinical myocardial dysfunction

›Protocol in MIS-C

›Cine imaging for LVEF and wall motion assessment

›T2 mapping for myocardial edema

›Late gadolinium enhancement for fibrosis detection

›Findings

›Myocardial edema on T2-weighted imaging in acute phase

›Late gadolinium enhancement in subset with significant myocardial injury

›Global longitudinal strain abnormal in 22% with otherwise normal LVEF

›Brain MRI

›Indicated for altered mental status, focal neurologic deficits, seizures

›Findings include encephalopathy, vascular changes, or white matter signal abnormality

›Exclude cerebral venous sinus thrombosis if coagulopathy present

CT

›CT abdomen and pelvis with contrast

›Indications: suspected acute abdomen or surgical emergency

›Differentiates appendicitis from MIS-C mesenteric lymphadenitis

›Findings in MIS-C: mesenteric lymphadenitis, bowel wall thickening, ascites, hepatomegaly

›Sensitivity for appendicitis > 94%

›Avoids unnecessary surgery in MIS-C mimic cases

›CT coronary angiography

›Indicated for suspected distal coronary artery aneurysms not well visualized on echocardiography

›Coronary artery aneurysms in approximately 13% of MIS-C cases

›Used when echo views are suboptimal (obese patients, older children)

›Giant aneurysm defined as internal diameter > 8 mm

›CT chest

›Indicated for respiratory failure evaluation

›Pleural effusions in 35% of cases

›Pulmonary edema from myocardial dysfunction

›Ground-glass opacities if acute COVID-19 pneumonitis coexists

Ultrasound

›Echocardiography — first-line cardiac investigation (essential in all cases)

›Indicated immediately upon MIS-C diagnosis

›Repeat at minimum every 24–48 hours in hemodynamically unstable patients

›Key measurements

›Left ventricular ejection fraction (LVEF)

›LV dysfunction in 20–55% of cases

›Coronary artery z-scores (body surface area-normalized)

›Z-score >= 2.5 indicates dilation

›Z-score >= 10 defines giant aneurysm

›Pericardial effusion assessment

›Present in approximately 23% of cases

›Valvular function (mitral, aortic regurgitation)

›Abdominal ultrasound

›First-line imaging for abdominal pain to exclude intussusception

›Mesenteric lymphadenopathy and bowel wall thickening in MIS-C

›Sensitivity for intussusception 98–100%

›Hepatomegaly and splenomegaly assessment

›Ascites quantification

›Point-of-care cardiac ultrasound

›Rapid LVEF estimation at bedside for hemodynamic decision-making

›Guides fluid resuscitation volume and vasopressor selection

›Identify pericardial effusion with tamponade physiology

07Disposition/dispo34

Admission indications

›Admission criteria — all patients meeting MIS-C case definition require hospital admission

›Abnormal vital signs (fever, tachycardia, hypotension, tachypnea)

›ICU admission required in 60–80% of cases

›Cardiac biomarker elevation (troponin or BNP)

›Any troponin elevation mandates cardiology evaluation

›Organ dysfunction in any system

›Renal, hepatic, hematologic, neurologic involvement

›Inability to maintain hydration orally

›PICU admission indications

›Shock requiring vasoactive agents

›Norepinephrine or milrinone infusion

›Significant LV dysfunction (LVEF < 45%)

›High-risk for cardiorespiratory deterioration

›Respiratory failure requiring non-invasive or mechanical ventilation

›Arrhythmias or conduction abnormalities

›AV block, sustained tachyarrhythmias

›Altered mental status or seizures

Level of care escalation

›ECMO consideration

›Refractory cardiorespiratory failure despite maximal medical therapy

›1.4% of large cohort cases required ECMO

›Venoarterial ECMO for cardiogenic shock

›Transfer criteria

›Transfer to PICU-capable center if ECMO may be required

›Children with severe biventricular failure or refractory shock

›Pediatric cardiac surgery center for giant coronary artery aneurysms

08Treatment/t77

Immunomodulatory therapy — first-line (ACR stepwise protocol)

›IVIG 2 g/kg IV over 10–12 hours

›Dose based on ideal body weight, maximum 100 g

›Do not exceed 100 g regardless of patient weight

›Monitor for IVIG infusion reactions

›Slow infusion rate if hypotension, flushing, or chills develop

›Patients with depressed LV function may need divided dosing

›1 g/kg/day x 2 days rather than single dose to reduce volume overload

›Concurrent furosemide 0.5–1 mg/kg if concern for fluid overload

›Do NOT repeat IVIG if refractory — risk of volume overload and hemolytic anemia

›Escalate to biologics or high-dose steroids instead

›Glucocorticoids — initiated concurrently with IVIG

›Methylprednisolone 1–2 mg/kg/day IV in divided doses (low-to-moderate)

›Equivalent to 1–2 mg/kg/day prednisolone orally when tolerating

›Continue for minimum 2–3 weeks with taper guided by clinical and laboratory response

›Steroid taper schedule

›Taper over 2–3 weeks guided by serial CRP, troponin, and echocardiogram

›Abrupt discontinuation risks rebound inflammation

Immunomodulatory therapy — refractory disease escalation

›Definition of refractory disease

›Persistent or recurrent fever >= 38.0 C after >= 24 hours of IVIG + steroids

›Rising or persistently elevated inflammatory markers

›Clinical deterioration despite first-line treatment

›High-dose pulse glucocorticoids

›Methylprednisolone 10–30 mg/kg/day IV x 1–3 days

›Maximum 1000 mg/day per pulse

›Monitor blood glucose q4–6h during pulse therapy

›Anakinra (IL-1 receptor antagonist)

›Dose > 4 mg/kg/day IV or subcutaneous

›Used for MAS overlap or IVIG/steroid-refractory disease

›Onset of action within 24–48 hours

›Biomarker-guided escalation in severe MAS features

›Infliximab (anti-TNF-alpha)

›5–10 mg/kg IV single dose

›Alternative to anakinra for refractory cases without MAS features

›Contraindicated if active bacterial infection or TB exposure

Antithrombotic therapy

›Low-dose aspirin

›3–5 mg/kg/day orally (maximum 81 mg/day) as antiplatelet therapy

›Indicated for coronary artery involvement (any dilation on echocardiography)

›Continue until coronary arteries normalize (typically 4–8 weeks)

›Higher dose aspirin (30–50 mg/kg/day in divided doses) during acute inflammatory phase only if tolerated

›Risk of Reye syndrome is theoretical but practice varies

›Anticoagulation

›Indicated for coronary artery aneurysm with z-score >= 10 (giant aneurysm)

›Low molecular weight heparin: enoxaparin 0.5–1 mg/kg SC q12h

›Target anti-Xa level 0.5–1.0 IU/mL for treatment dosing

›Anticoagulation for significant thrombocytosis (> 800 x10^9/L) with coronary dilation

›Wide practice variation — guided by cardiology and hematology

Hemodynamic support

›Fluid resuscitation

›0.9% sodium chloride or lactated Ringer's 10–20 mL/kg bolus

›Reassess after each bolus (capillary refill, HR, BP, urine output)

›Maximum 40–60 mL/kg in first hour; consider vasopressors earlier if LV dysfunction

›Vasoactive agents

›Norepinephrine 0.05–0.5 mcg/kg/min for vasodilatory/distributive shock

›Titrate to age-appropriate mean arterial pressure

›Milrinone 0.25–0.75 mcg/kg/min for cardiogenic shock with reduced LVEF

›Combine with norepinephrine if systemic vascular resistance is low

›Epinephrine 0.05–0.3 mcg/kg/min for refractory shock

›Second-line after norepinephrine

›Inotropic support

›Dobutamine 2.5–10 mcg/kg/min for cardiogenic shock with adequate blood pressure

›Risk of worsening hypotension from vasodilation

Antibiotic therapy

›Empiric antibiotics until bacterial sepsis excluded

›Broad-spectrum coverage: piperacillin-tazobactam 75–100 mg/kg q8h IV (piperacillin component)

›Adjust for local antibiogram and renal function

›Discontinue within 24–48 hours if cultures negative and MIS-C diagnosis confirmed

›Vancomycin 15 mg/kg IV q6h if MRSA risk present

›Target AUC/MIC-guided dosing

›Renal function monitoring every 24 hours

Respiratory support

›Supplemental oxygen

›Titrate to SpO2 >= 94%

›High-flow nasal cannula for increased oxygen demand

›Non-invasive positive pressure ventilation for mild-moderate respiratory failure

›CPAP or BiPAP with appropriate pediatric interface

›Mechanical ventilation

›Lung-protective strategy if intubated

›Tidal volume 6 mL/kg ideal body weight

›PEEP 5–8 cmH2O, titrate to oxygenation

›Plateau pressure < 30 cmH2O

09Special Populations/sp54

Pregnancy

›MIS-C specific context

›MIS-C by case definition requires age < 21 years

›Adolescent pregnancy (< 21 years) is possible and relevant

›Rare case reports of SARS-CoV-2 related hyperinflammatory syndromes in pregnant adolescents

›Classified separately from classic MIS-C in most guidelines

›IVIG safety in pregnancy

›IVIG considered safe in pregnancy — FDA category C

›No teratogenic effects established

›Hemolytic anemia risk remains regardless of pregnancy

›Glucocorticoid safety in pregnant adolescents

›Methylprednisolone preferred over dexamethasone for maternal rather than fetal indication

›Dexamethasone crosses placenta and may accelerate fetal lung maturity

›Monitor for gestational glucose elevation with pulse steroids

›Fetal monitoring

›Continuous fetal heart rate monitoring if > 24 weeks gestation

›Maternal tachycardia and hypotension affect fetal perfusion

›Obstetric consultation immediately upon MIS-C diagnosis in pregnant adolescent

Geriatric

›MIS-A context (MIS in Adults)

›MIS-C definition requires age < 21 years — equivalent syndrome in adults termed MIS-A

›Older adolescents (18–20 years) occasionally described in adult cohorts

›Similar pathophysiology but different inflammatory biomarker thresholds

›No true geriatric population applies to MIS-C

›Late adolescents (16–20 years) have adult body weight — dosing implications

›IVIG dose still capped at 100 g maximum regardless of weight

›Methylprednisolone dosing same weight-based protocol

›Older adolescents more likely to develop myocarditis and shock phenotype

10Background/b70

Epidemiology

›Incidence and prevalence

›First described in April–May 2020 in UK children following initial COVID-19 surge

›Confirmed as distinct entity by CDC, WHO, and RCPCH in May–June 2020

›Incidence approximately 1–2 per 10,000 SARS-CoV-2 infections in children

›Total US cases exceeded 8,000 by 2022 with ongoing surveillance

›Incidence decreased substantially following widespread pediatric COVID-19 vaccination

›COVID-19 vaccination reduces MIS-C risk

›Demographics

›Median age 8–9 years (range 0–20 years)

›Broader age distribution than Kawasaki disease (typically < 5 years)

›Male predominance: 57–59% of cases

›Racial and ethnic disparities

›Disproportionate incidence in Black, Afro-Caribbean, and Hispanic children

›Biological and socioeconomic factors under investigation

›Severity and outcomes

›ICU admission required in 60–80% of cases

›Vasoactive support required in 50–73%

›ECMO required in 1.4% of large cohorts

›Mortality 1.4–1.9% — notably most fatalities in previously healthy children

›Long-term outcomes

›MUSIC study (1,204 participants): 95% returned to > 90% of pre-illness health by 6 months

›Nearly all LV dysfunction and coronary aneurysms resolved by 6 months

›21% had persistently abnormal global longitudinal strain at 2 months suggesting subclinical dysfunction

Pathophysiology

›Relationship to SARS-CoV-2

›Postinfectious hyperinflammatory disorder occurring 2–6 weeks after SARS-CoV-2 infection

›Temporal pattern consistent with immune-mediated rather than direct viral mechanism

›PCR often negative at MIS-C presentation — serology typically positive

›Immune dysregulation hypothesis

›Dysregulated innate and adaptive immune response to SARS-CoV-2 antigens

›Molecular mimicry and autoantibody formation proposed

›Cytokine storm with elevated IL-6, IL-10, TNF-alpha, IFN-gamma

›Cardiovascular pathology

›Myocardial inflammation and dysfunction

›LV dysfunction in 20–55% of acute cases

›Mechanism includes direct cytokine-mediated myocardial injury and vasculitis

›Coronary artery involvement

›Dilation or aneurysm formation in approximately 13% of cases

›Pathophysiology similar to Kawasaki vasculitis — vessel wall inflammation

›Pericardial involvement

›Effusion in 23% — rarely causes tamponade

›Gastrointestinal pathology

›Mesenteric vasculitis causing abdominal pain and bowel wall edema

›Lymphadenitis from immune cell infiltration of mesenteric nodes

›Can mimic acute surgical abdomen

›Coagulopathy

›Hypercoagulable state from endothelial injury and cytokine-mediated procoagulant shift

›Markedly elevated D-dimer (median 3,578 ng/mL)

›Risk of coronary artery thrombus especially with aneurysm formation

Therapeutic Considerations

›ACR stepwise immunomodulatory approach

›Basis for treatment protocol

›Class I evidence supporting combined IVIG + glucocorticoids over IVIG alone

›RCT evidence (RECOVERY-Plus) supports combined therapy for moderate-severe MIS-C

›Algorithm

›Step 1: IVIG 2 g/kg + methylprednisolone 1–2 mg/kg/day

›Step 2 (refractory): Pulse methylprednisolone 10–30 mg/kg/day

›Step 3 (biologic escalation): Anakinra or infliximab

›Biomarker-guided therapy

›CRP and ferritin normalization target before steroid taper

›Serial troponin and BNP to confirm cardiac recovery

›Coronary artery z-score normalization on serial echocardiography

›Antiplatelet and anticoagulation evidence

›Low-dose aspirin: ACR Class I recommendation for coronary involvement

›Continue until z-scores normalize (typically 4–8 weeks)

›Anticoagulation evidence: wide practice variation, expert consensus

›Giant aneurysms (z-score >= 10) require dual antiplatelet or anticoagulation per AHA guidelines

›Follow-up monitoring schedule

›1–2 weeks: Repeat labs, ECG, echocardiogram

›4–6 weeks: Repeat echocardiogram, labs, ECG

›4–6 months: Cardiac MRI if initial LVEF < 50%

›10–12 months: Echocardiogram if cardiac abnormalities during acute phase

11Patient Discharge Instructions/pdi37

copy discharge instructions

›Diagnosis explanation

›Your child was diagnosed with Multisystem Inflammatory Syndrome in Children (MIS-C)

›MIS-C is a rare inflammatory condition that occurs several weeks after COVID-19 infection

›It caused inflammation in multiple organs including the heart

›Treatment with IVIG and steroids helps control the inflammation

›Medications to continue at home

›Take all prescribed medications exactly as instructed

›Aspirin: low-dose aspirin as directed by your cardiologist — do not stop without guidance

›Steroids: take steroid pills as prescribed — do not stop suddenly

›Report any new medications or supplements to your doctor before starting

›Avoid ibuprofen (Advil, Motrin) unless specifically directed by your doctor

›May interact with aspirin or affect platelet function

›Activity restrictions

›No strenuous physical activity or organized sports until cleared by cardiology

›Your child's heart needs time to recover fully

›Avoid PE class, competitive sports, and any vigorous activity

›Return-to-sports requires a normal echocardiogram and cardiology clearance

›Light activity (slow walking, quiet play) is generally acceptable

›Follow-up appointments

›Cardiology appointment within 1–2 weeks — this is mandatory

›Bring all discharge papers and medication list to the appointment

›Repeat echocardiogram at 4–6 weeks after discharge

›Repeat blood tests 1–2 weeks after discharge as arranged

›Return to emergency department immediately if any of the following occur

›Recurrent fever > 38.0 C

›Could signal return of inflammation or new infection

›Chest pain, palpitations, or difficulty breathing

12References/r32

Guidelines and key sources

›American College of Rheumatology (ACR) Clinical Guidance

›Henderson LA, Canna SW, Friedman KG, et al. ACR Clinical Guidance for MIS-C Associated With SARS-CoV-2 and Hyperinflammation in Pediatric COVID-19: Version 3. Arthritis Rheumatology. 2022

›Primary stepwise immunotherapy protocol: IVIG + steroids, biological escalation

›Basis for antithrombotic and anticoagulation recommendations

›Version 2: Henderson LA et al. Arthritis Rheumatology. 2021

›American Heart Association (AHA) Scientific Statements

›Jone PN, John A, Oster ME, et al. SARS-CoV-2 Infection and Associated Cardiovascular Manifestations in Children and Young Adults. Circulation. 2022

›Echocardiography indications and coronary artery z-score monitoring

›Jone PN, Tremoulet A, Choueiter N, et al. Update on Diagnosis and Management of Kawasaki Disease. Circulation. 2024

›Comparative guidance for Kawasaki disease vs MIS-C distinction

›Landmark epidemiological studies

›Feldstein LR, Rose EB, Horwitz SM, et al. Multisystem Inflammatory Syndrome in US Children and Adolescents. NEJM. 2020

›First major US cohort describing epidemiology and outcomes

›Feldstein LR, Tenforde MW, Friedman KG, et al. Characteristics and Outcomes of US Children With MIS-C Compared With Severe Acute COVID-19. JAMA. 2021

›Comparative outcomes data, ICU admission rates, vasoactive support frequency

›McArdle AJ, Vito O, Patel H, et al. Treatment of MIS-C. NEJM. 2021

›Treatment response data, biomarker normalization, comparative effectiveness

›Pathophysiology and immune mechanisms

›Feleszko W, Okarska-Napierala M, Buddingh EP, et al. Pathogenesis, Immunology, and Immune-Targeted Management of MIS-C/PIMS. Pediatric Allergy and Immunology. 2023

›EAACI position paper on cytokine storm and immune dysregulation

›Long-term outcome studies

›Truong DT, Trachtenberg FL, Hu C, et al. Six-Month Outcomes in the LOMIS Study. JAMA Pediatrics. 2025

›Long-term cardiac and functional outcomes

›El Rassi C, El Darzi R, Abou Mansour M, Arabi M. MIS-C: Diagnosis, Management, and Outcomes. Open Forum Infectious Diseases. 2026

›Global longitudinal strain as early subclinical dysfunction marker

›Maddux AB, Berbert L, Young CC, et al. Health Impairments After Hospitalization for Acute COVID-19 or MIS-C. Pediatrics. 2022

›Recovery trajectory and residual morbidity

Evidence & Review

Evidence & Review