Clinical Scenario:
A 7-year-old boy is brought to the emergency department with 2 days of persistent fever, severe abdominal pain and vomiting. Over the preceding 6 hours, he has become increasingly lethargic and developed cold extremities. Four weeks earlier, he had a mild febrile respiratory illness that resolved spontaneously.
On examination, temperature is 38.7°C, heart rate 142/min, blood pressure 82/48 mmHg, capillary refill 5 seconds and SpO₂ 94% on room air. He has bilateral non-purulent conjunctival injection and a faint maculopapular rash. There is mild hepatomegaly but no clinical evidence of bleeding.
Investigations show Hb 11.8 g/dL, WBC 17.2 × 10⁹/L with neutrophilia and lymphopenia, platelets 92 × 10⁹/L, CRP 248 mg/L, ferritin 1,480 ng/mL and markedly elevated D-dimer. Troponin is significantly elevated. Echocardiography shows global left ventricular systolic dysfunction with an ejection fraction of 35%. SARS-CoV-2 PCR is negative, but SARS-CoV-2 IgG is strongly positive.
Which of the following is the most likely diagnosis?
A. Dengue shock syndrome
B. Kawasaki disease
C. Meningococcal septic shock
D. Multisystem inflammatory syndrome in children
E. Severe acute COVID-19
Correct answer & Explanation:
Correct answer: D. Multisystem inflammatory syndrome in children (MIS-C)
Explanation
This child has a classic post–SARS-CoV-2 hyperinflammatory presentation consistent with MIS-C.
The important diagnostic clues are:
- Fever occurring approximately 4 weeks after a preceding SARS-CoV-2-compatible illness
- Shock and hypotension
- Prominent gastrointestinal involvement with abdominal pain and vomiting
- Conjunctival injection and rash
- Markedly elevated inflammatory markers
- Lymphopenia and thrombocytopenia
- Markedly elevated D-dimer
- Cardiac involvement with elevated troponin and LV systolic dysfunction
- Positive SARS-CoV-2 serology despite a negative PCR
MIS-C commonly presents several weeks after SARS-CoV-2 infection and may involve the gastrointestinal, mucocutaneous, hematologic and cardiovascular systems. Severe cases can develop myocardial dysfunction and shock.
The negative PCR does not argue against MIS-C. By the time MIS-C develops, active viral replication may have resolved, while SARS-CoV-2 antibodies remain detectable. The timing and multisystem inflammatory phenotype are much more important than PCR positivity alone.
Why the other options are less likely
A. Dengue shock syndrome:
Dengue can produce fever, abdominal pain, thrombocytopenia and shock, making it an important differential. However, the marked hyperinflammation, conjunctival injection, post-SARS-CoV-2 timing and myocardial dysfunction with elevated troponin strongly favor MIS-C. In an endemic setting, dengue testing should nevertheless be performed when clinically appropriate.
B. Kawasaki disease:
Kawasaki disease can cause fever, conjunctival injection, rash and cardiac involvement, but this child has prominent shock, gastrointestinal symptoms, thrombocytopenia, markedly elevated D-dimer and myocardial dysfunction in a post-SARS-CoV-2 setting, making MIS-C more likely.
C. Meningococcal septic shock:
Meningococcal disease can cause rapidly progressive shock, but the preceding SARS-CoV-2 illness, strong serologic evidence and multisystem inflammatory phenotype favor MIS-C. Blood cultures and appropriate microbiological evaluation are still essential because bacterial sepsis must be excluded.
E. Severe acute COVID-19:
Severe acute COVID-19 is primarily a respiratory illness. This child has no significant respiratory disease; instead, he has a post-infectious inflammatory syndrome with gastrointestinal, mucocutaneous, hematologic and cardiovascular involvement.
Exam pearl
Think MIS-C when a child presents several weeks after SARS-CoV-2 infection with:
fever + gastrointestinal symptoms + mucocutaneous features + marked inflammation ± shock/myocardial dysfunction.
The combination of shock and LV dysfunction is particularly important because cardiovascular involvement is common in severe MIS-C.
Reference
World Health Organization. Clinical management of COVID-19: living guideline — case definitions of MIS-C. WHO. The WHO definition includes fever ≥3 days, multisystem involvement, elevated inflammatory markers, absence of another obvious microbial cause, and evidence of SARS-CoV-2 infection or exposure.
Centers for Disease Control and Prevention (CDC). Clinical Overview of Multisystem Inflammatory Syndrome in Children (MIS-C). Updated December 16, 2025.
