(1499) Mitochondrial Dysfunction and Hyperinflammation in Pediatric COVID-19 Infection

Introduction: COVID-19 caused by SARS-CoV-2 causes a multisystem inflammatory syndrome (MIS-C) in some children. There are several case reports of hemophagocytic lymphohistiocytosis (HLH) associated with COVID-19 infection. We present a case of a child with COVID-19 infection presenting in severe multisystem organ failure and hyperinflammatory state mimicking HLH with clinical features of mitochondrial dysfunction.

Description: A 3-year-old boy otherwise healthy except for mild neurodevelopmental delay presented with severe shock, multi-organ dysfunction including acute liver and renal failure, hypoglycemic seizure, and PEA arrest, in the setting of COVID-19 infection. Diagnosis of primary or secondary HLH was the initially suspected etiology of hyperinflammation due to fever, elevated ferritin (37,000 ng/mL), cytopenias, thrombocytopenia, and hypofibrinogenemia. Therefore, he was treated with methylprednisolone and anakinra resulting in significant clinical improvement. During a failed extubation attempt, he developed a rapid onset severe lactic acidosis (rise from 2.4 to 13 mmol/L) with hypercarbic respiratory failure. Additionally, he had high creatine kinase (peak 26,847 IU/L), acute renal failure, and an unusual maternal family history of multiple unexplained deaths in infancy and early childhood, which raised suspicion for a mitochondrial disorder. He was treated empirically with thiamine and levocarnitine. On diagnostic evaluation, bone marrow aspirate and lumbar puncture were negative for malignant cells or hemophagocytosis, and testing was negative for a mitochondrial genetic disorder. Whole genome sequencing showed chromosome a 16p11.2 duplication, which was related to his developmental delay, but not his severe illness presentation. With immunomodulatory therapy, the patient fully recovered to prior baseline with no apparent long-term sequelae.

Discussion: Severe multiorgan system failure associated with MIS-C in COVID-19 pediatric patients can present with clinical features of hyperinflammation and mitochondrial dysfunction in the absence of genetic diagnosis of mitochondrial disease or histologic evidence of HLH. These patients may respond favorably to early immunomodulatory therapy and supportive care for mitochondrial dysfunction.