P2A222: COVID-19 with Streptococcal Infection, Hemolytic Uremic Syndrome, Hemophagocytic Lymphohistiocytosis

Introduction: SARS-CoV-2 can cause a spectrum of illness ranging from mild to severe and may be associated with bacterial and viral co-infection and immune-dysregulation. Factors that contribute to increased morbidity and mortality as well as optimal treatment are still being studied. We describe a complicated pediatric case of SARS-CoV-2 with bacterial coinfection, multiorgan failure, thrombotic microangiopathy, and systemic hyperinflammation. Consensus is lacking on safe treatment methods that balance antimicrobial and immunomodulatory therapies.

Case Description: A two-year-old healthy male presented with one week of fevers and respiratory failure. Initial chest x-ray showed bilateral dense lower lobe consolidations and left sided pleural effusion. COVID-19 and rhinovirus polymerase chain reactions were positive. He was placed on bilevel positive airway pressure due to respiratory distress, and he was given dexamethasone for COVID pneumonia and ceftriaxone for pulmonary infiltrates. Due to the duration of symptoms prior to presentation, he was not initiated on remdesivir therapy. His blood culture drawn on admission grew pansensitive Streptococcus pneumoniae. He developed microangiopathic hemolytic anemia (hemoglobin as low as 3.0 g/dL), thrombocytopenia (platelet nadir 20 k/uL), and acute kidney injury (creatinine peak 1.12 mg/dL), consistent with a diagnosis of Streptococcus pneumoniae-associated hemolytic uremic syndrome (SP-HUS). Hemolysis and thrombocytopenia worsened despite antibiotics, thus eculizumab was added. The patient was transfused only with washed red blood cells to limit further exposure to T-antigen. He had persistent high fevers and subsequently developed pancytopenia, hypertriglyceridemia, and hyperferritinemia (peak ferritin 7,793 ng/mL), concerning for secondary hemophagocytic lymphohistiocytosis (HLH). Anakinra was chosen as HLH therapy with the hope of limiting further immunosuppression in the setting of active infections. Soon after, his hemolysis, kidney injury, and ferritin significantly improved. His illness was further complicated by necrotizing pneumonia with bilateral pneumothraces requiring multiple chest tubes. An immune workup including whole exome sequencing was unremarkable. Our patient’s respiratory failure was managed exclusively with non-invasive ventilation and his renal injury with supportive care, fortunately never requiring intubation or dialysis. He improved and was discharged home on hospital day 32 on nasal cannula oxygen therapy.

Discussion: SARS-CoV-2 and concurrent illness can be difficult to treat due to the nuanced balance between treating active infection, hyperinflammation, and immune dysregulation. We describe a pediatric patient with COVID-19 pneumonia, bacterial superinfection, SP-HUS, and HLH, whom we successfully managed with anakinra and eculizumab in addition to standard of care antibiotics and steroids.

Conclusion: Our experience suggests that anakinra and eculizumab should be considered in critically ill patients with severe infections that require immunomodulating therapies for life-threatening dysregulation.