What are the diagnostic criteria for Multisystem Inflammatory Response Syndrome (MIRS) in Covid-19?

Diagnostic Criteria for Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19

Diagnose MIS-C using a tiered laboratory approach combined with clinical features and confirmed SARS-CoV-2 exposure, starting with screening labs (CBC, CMP, ESR, CRP, SARS-CoV-2 PCR/serology) and progressing to complete evaluation if initial markers are suggestive. 1

Essential Diagnostic Components

1. Epidemiologic Link to SARS-CoV-2 (Required)

The child must have any one of the following: 1

• Positive SARS-CoV-2 PCR test
• Positive SARS-CoV-2 serology (IgG, IgM, or IgA if available)
• Preceding illness resembling COVID-19
• Close contact with confirmed or suspected COVID-19 case within the past 4 weeks

2. Clinical Features (Must Be Present)

Fever is the cardinal feature, accompanied by multisystem involvement including: 1

Mucocutaneous findings:

• Polymorphic, maculopapular, or petechial rash (not vesicular)
• Bilateral conjunctivitis without exudate
• Red and/or cracked lips
• Strawberry tongue
• Erythema of oropharyngeal mucosa
• Edema of hands/feet

Gastrointestinal symptoms:

• Diarrhea
• Abdominal pain
• Vomiting

Cardiac manifestations:

• Myocardial dysfunction
• Cardiac conduction abnormalities
• Shock

Neurologic symptoms:

• Altered mental status or encephalopathy
• Focal neurologic deficits
• Meningismus
• Papilledema
• Severe headache
• Cranial nerve palsies

Other features:

• Lymphadenopathy

3. Tiered Laboratory Evaluation

Tier 1 - Initial Screening (Send Immediately): 1

• CBC (complete blood count)
• CMP (complete metabolic panel including sodium, potassium, CO2, chloride, BUN, creatinine, glucose, calcium, albumin, total protein, AST, ALT, alkaline phosphatase, bilirubin)
• ESR (erythrocyte sedimentation rate)
• CRP (C-reactive protein)
• SARS-CoV-2 PCR and/or serologies

Tier 2 - Complete Full Diagnostic Evaluation (If Tier 1 Suggestive): 1

Proceed to complete evaluation if either criterion is met:

Criterion 1 (any one):

• CRP >25 mg/dL
• ESR >40 mm/hour

Criterion 2 (at least two):

• Elevated BNP (B-type natriuretic peptide)
• Elevated troponin T
• Absolute lymphocyte count <1,000/µL
• Platelet count <150,000/µL
• Sodium <135 mmol/L

Additional studies for complete evaluation: 1

• Procalcitonin (if available)
• Cytokine panel (if available)
• SARS-CoV-2 IgG, IgM, and IgA (if not sent in Tier 1)
• Electrocardiogram (EKG)
• Echocardiogram
• Coagulation studies (PT, PTT, D-dimer, fibrinogen)

4. Additional Diagnostic Studies Based on Clinical Presentation

May require: 1

• Chest imaging (X-ray or CT)
• Abdominal imaging (ultrasound or CT)
• Central nervous system imaging (MRI or CT)
• Lumbar puncture (if neurologic symptoms present)

Critical Pitfalls to Avoid

Maintain broad differential diagnosis: MIS-C findings are nonspecific and overlap with other infections, malignancy, and inflammatory conditions—always evaluate for alternative diagnoses concurrently. 1

Temporal considerations: MIS-C typically emerges 2-6 weeks after peak COVID-19 incidence in a geographic area; local epidemiology should inform diagnostic suspicion. 1

SARS-CoV-2 PCR may be negative: Many children with MIS-C have negative PCR because the syndrome occurs weeks after acute infection—serology is often the only positive test. 1, 2

Distinguish from Kawasaki disease: While clinical features overlap, MIS-C patients are typically older, have more prominent gastrointestinal symptoms, more frequent shock, and higher inflammatory markers than classic Kawasaki disease. 1

Admission Criteria

Admit for observation if any of the following are present: 1

• Abnormal vital signs (tachycardia, tachypnea)
• Respiratory distress of any severity
• Neurologic deficits or change in mental status (including subtle manifestations)
• Evidence of even mild renal or hepatic injury
• Marked elevations in inflammation markers (CRP ≥10 mg/dL)
• Abnormal EKG findings or abnormal levels of BNP or troponin T

Immediate admission required for: 1

• Shock
• Significant respiratory distress
• Neurologic changes (altered mental status, encephalopathy, focal deficits, meningismus, papilledema)
• Dehydration
• Features of Kawasaki disease

Multidisciplinary Management

Children admitted with MIS-C require consultation with: 1

• Pediatric rheumatology
• Pediatric cardiology
• Pediatric infectious disease
• Pediatric hematology
• Additional subspecialties as clinically indicated (neurology, nephrology, hepatology, gastroenterology)

Cardiac Monitoring Requirements

Echocardiogram schedule: 3

• At diagnosis
• 7-14 days after presentation
• 4-6 weeks after presentation
• More frequent monitoring if LV dysfunction or coronary artery aneurysms present

EKG monitoring: 3

• Every 48 hours minimum while hospitalized
• During follow-up visits
• Continuous telemetry if conduction abnormalities present

Cardiac biomarkers: 3

• Trend BNP and troponin T until normalization