What is the recommended treatment and management for multisystem inflammatory syndrome in adults (MIS‑A) presenting with fever, elevated inflammatory markers, and involvement of two or more organ systems after SARS‑CoV‑2 infection?

Multisystem Inflammatory Syndrome in Adults (MIS-A): Treatment and Management

For adults presenting with MIS-A after SARS-CoV-2 infection, immediate treatment with intravenous immunoglobulin (IVIG) and corticosteroids is recommended, with consideration of IL-1 receptor antagonists (anakinra) for severe cases, particularly those with hemodynamic compromise or cardiogenic shock. 1

Diagnostic Criteria and Recognition

MIS-A should be suspected in adults presenting 2-8 weeks after SARS-CoV-2 infection (median 4 weeks) with: 2, 3

• Fever and elevated inflammatory markers (CRP, ferritin, D-dimer, IL-6) 4, 2
• Cardiac involvement (present in nearly all cases) - including chest pain, elevated troponin, ECG abnormalities, and ventricular dysfunction 2, 5
• Secondary organ involvement - most commonly gastrointestinal symptoms (abdominal pain, vomiting, diarrhea), followed by shock/hypotension 2, 6
• Laboratory confirmation of recent SARS-CoV-2 infection (positive PCR, antigen test, or serology) 6

Importantly, MIS-A affects predominantly young adults (mean age ~33 years) and occurs regardless of comorbidity status - 70% of reported cases had no significant medical history. 2

Initial Evaluation and Hospitalization

When MIS-A is suspected, perform the triad of cardiac testing: 1

• ECG (look for ST-segment elevation, diffuse T-wave inversion, QRS prolongation)
• Cardiac troponin (preferably high-sensitivity assay)
• Echocardiogram (assess for ventricular dysfunction and wall motion abnormalities)

Immediate cardiology consultation is warranted for rising troponin and/or ECG/echocardiographic abnormalities. 1

Hospitalization is mandatory for definite MIS-A, ideally at an advanced heart failure center given the high rate of ICU admission (>50% of cases) and potential for cardiogenic shock. 1, 2 Patients with fulminant presentations require centers with expertise in mechanical circulatory support. 1

Treatment Algorithm

First-Line Immunomodulatory Therapy

Intravenous corticosteroids should be administered for suspected or confirmed MIS-A, particularly with hemodynamic compromise - this approach has been associated with favorable prognosis. 1, 5, 3 The American College of Cardiology specifically recommends IV corticosteroids for MIS-A as a hyperinflammatory state with acute heart failure and/or cardiogenic shock in the absence of sepsis. 1

IVIG is commonly used in combination with corticosteroids based on treatment patterns from case series showing rapid clinical improvement. 4, 5, 3

Second-Line Biologic Therapy

IL-1 receptor antagonist (anakinra) should be considered for severe cases or those not responding adequately to initial therapy. 5, 3 In a Swedish case series, the combination of IVIG, pulse steroids, and anakinra resulted in rapid clinical improvement in critically ill patients. 3

Concurrent COVID-19 Pneumonia

If the patient has concurrent COVID-19 pneumonia requiring supplemental oxygen, corticosteroids are definitively indicated. 1

Pericardial Involvement

For associated pericardial disease, add: 1

• NSAIDs for chest pain and inflammation
• Colchicine (low-dose) or prednisone for persistent symptoms

Heart Failure Management

Guideline-directed medical therapy for heart failure should be initiated before discharge and continued long-term: 1

• Low-dose aldosterone antagonist for mildly reduced LV systolic function with stable hemodynamics
• Beta-blocker (if hemodynamically stable) - particularly helpful for supraventricular arrhythmias
• Caution: Beta-blockade can precipitate cardiogenic shock in severely compromised cardiac function 1

Cardiac Magnetic Resonance Imaging

CMR is recommended in hemodynamically stable patients with suspected myocarditis to confirm diagnosis and assess extent of inflammation. 1 Once stabilized from cardiogenic shock, CMR should be performed before hospital discharge. 1

Critical Pitfalls to Avoid

• Do not delay treatment waiting for CMR or other confirmatory testing in unstable patients - initiate immunomodulation based on clinical suspicion 5
• Do not dismiss the diagnosis in older adults or those with comorbidities - while mean age is 33 years, MIS-A can occur at any age 2, 7
• Do not confuse with sepsis - MIS-A is a hyperinflammatory state occurring in the absence of sepsis, though sepsis can co-occur 1, 5
• Watch for glucose intolerance and unmasking of autoimmune disease as potential features 5

Activity Restriction and Follow-Up

Strenuous physical activity must be avoided for 3-6 months following diagnosis. 1

Structured follow-up surveillance testing is essential and should include: 1

• ECG
• Echocardiogram
• Ambulatory rhythm monitoring
• Repeat CMR to assess resolution of inflammation

This monitoring serves to gauge cardiac function recovery, guide heart failure management, and assess prognosis. 1

Prognosis

Despite the severity of presentation and high ICU admission rates (>50%), mortality is relatively low (approximately 5-6% in case series) with prompt recognition and aggressive immunomodulatory treatment. 2, 5 Most patients achieve full recovery, though a subset experiences persistent complications requiring ongoing surveillance. 4, 5