on hospital day 3, the patient had an acute change in mental status, including confusion and global aphasia. An emergent computed tomography scan of the head was negative for cerebrovascular accident and showed normal brain parenchyma and no evidence of acute infarction, mass, or hemorrhage. On completion of the scan, the patient was found nonresponsive and without a pulse. He underwent multiple rounds of advanced cardiac life support, resulting in return of spontaneous circulation. A chest radiograph showed an enlarged cardiac silhouette, and an echocardiogram showed severe biventricular dysfunction, severe global hypokinesis of the left ventricle, and left ventricular ejection fraction of 20%. The patient received a second dose of IVIg and intravenous steroids and extracorporeal membrane oxygenation support was initiated. On hospital day 4, severe multisystem organ failure continued to progress. The patient died on hospital day 4.We reviewed the patient’s medical history and clinical chart. We assessed serum samples collected during the hospital course before and after IVIg, and we determined endpoint titers to SARS-CoV-2 nucleocapsid (IgM and IgG) and spike receptor binding domain with neutralization functions against spike protein (6,7). The endpoint titer was a modified protocol based on Stadlbauer et al. (8). We completed an autopsy and sent formalin-fixed, paraffin-embedded tissues to CDC. Microscopic examination of lung, airways, pulmonary lymph node, liver, heart, spleen, kidneys and stomach tissue samples was performed; LT-Gram stain was performed on lungs and heart. An RT-PCR assay for SARS-CoV-2 was performed on RNA extracted from formalin-fixed, paraffin-embedded tissues from lungs, airways, and heart by methods previously published (9). This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.Serum antibody results drawn before IVIg infusion were negative for SARS-CoV-2 IgM but positive for IgG. Serum results had a high titer of anti-spike receptor binding domain antibody both before and after IVIg (1:75,000) compared with a naturally infected SARS-CoV-2–positive control (1:4,000). In addition, the pre-IVIG sample serum results demonstrated neutralizing function.Histopathologic findings in a fatal case of multisystem inflammatory syndrome in adult after natural severe acute respiratory syndrome coronavirus 2 infection and coronavirus disease vaccination, Tennessee, USA, 2021. A) Lung tissue shows capillaritis characterized by neutrophilic inflammation and necrosis within interalveolar septa (arrowhead). Fibrin and organizing intraluminal microthrombi in small arteries are also seen (arrows). Original magnification 20×. B) Higher magnification of fibrin microthrombus within a lung vessel (arrow). Original magnification 63×. C) Heart tissue shows myocarditis with myocyte necrosis and mixed inflammatory infiltrate. Original magnification 20×. D) Higher magnification cardiac vessel showing microthrombus and perivascular mononuclear inflammatory infiltrate (arrow). Original magnification 40×. E) Stomach tissue shows submucosal microthrombi with perivascular lymphocytic infiltrate. Original magnification 63×. F) Kidney tissue shows multiple fibrin thrombi in glomerular (arrow) and interstitial capillaries (arrow). Original magnification 40×.. Histopathologic findings in a fatal case of multisystem inflammatory syndrome in adult after