Multisystem inflammatory syndrome in children (MIS-C) represents a severe postinfectious hyperinflammatory condition following SARS-CoV-2 infection. Despite extensive clinical characterization, histopathologic data—especially from pre-mortem pediatric biopsies—remain scarce.

We report a 9-month-old male infant with confirmed SARS-CoV-2 infection and rapid multiorgan failure. Pre-mortem incisional biopsies from the myocardium, lung, and pleura revealed degenerative myocyte changes, endothelial swelling, and fibrin-platelet microthrombi consistent with thrombotic microangiopathy. Immunohistochemistry demonstrated mild CD3+ T-cell–predominant infiltrates and focal SARS-CoV-2 antigen positivity confined to alveolar and bronchiolar epithelium, while myocardial and pleural tissues were negative.

These findings highlight early morphologic correlates of immune-mediated vascular injury in MIS-C, characterized by endothelial dysfunction, microvascular inflammation, and T-cell-driven immunopathology in the absence of direct viral cytopathy. This case provides rare pre-mortem evidence of immune-thrombotic endotheliopathy in an infant, bridging clinical and histologic manifestations of pediatric SARS-CoV-2–associated hyperinflammatory disease.