Pathophysiological Connection between MIS-C Following SARS-CoV-2 Infection and Kawasaki Disease: The Role of ACE2 Expression

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), invades host cells through the angiotensin-converting enzyme 2 (ACE2) receptor, leading to cellular injury. Because ACE2 is expressed not only in the lungs but also in vascular endothelium, the heart, kidneys, and gastrointestinal tract, infection can result in multiorgan involvement. SARS-CoV-2 infection disrupts the renin–angiotensin–aldosterone system (RAAS), promoting vasoconstriction and fibrosis, while activation of the coagulation pathway accelerates thrombus formation. In addition, hyperactivation of the innate immune system triggers excessive inflammation. Although COVID-19 in children and adolescents is generally mild or asymptomatic, some develop multisystem inflammatory syndrome in children (MIS-C) several weeks after infection. We describe two children who developed MIS-C after SARS-CoV-2 infection. Both had fever persisting for more than three days, raised cardiac biomarkers, and impaired left ventricular systolic function on echocardiography, with an ejection fraction below 45%. Serologic testing confirmed previous SARS-CoV-2 exposure in each case. The first patient exhibited signs that resembled incomplete Kawasaki disease (KD), such as conjunctival injection, a truncal erythematous rash, and swelling of the hands and feet. In contrast, the second patient presented with acute endocarditis and myocarditis, accompanied by a thrombus in the right ventricle. Treatment consisted of intravenous immunoglobulin, methylprednisolone, and antithrombotic agents. Their cardiac function improved completely, and both recovered without residual complications. This report emphasizes the importance of distinguishing MIS-C from KD in clinical practice. It also raises the possibility that their overlapping features may stem from a shared pathophysiological process linked to ACE2 expression.