Severe Pediatric COVID-19 Pneumonia Treated With Adjuvant Anakinra

Abstract

OBJECTIVES To compare prior hemophagocytic lymphohistiocytosis (HLH) criteria to adult COVID-19-associated hyperinflammatory syndrome (cHIS) criteria for the diagnosis of hyperinflammation in pediatric patients with COVID-19. The secondary objective was to assess treatment response to intravenous (IV) anakinra in these patients. METHODS This case series included children admitted to the pediatric intensive care unit (PICU) for COVID-19 pneumonia with hyperinflammation and treated with IV anakinra between July 2020 to April 2021. Hyperinflammatory criteria were determined for each patient. Clinical course, chest imaging, and inflammatory marker trends were assessed pre- and post-anakinra treatment. RESULTS All patients had a cHIS criteria score of >5. Two patients met 2004-HLH criteria. Only the patient that required extracorporeal membrane oxygenation (ECMO) met the H-Score cut-off value. All but one patient had a decrease in their inflammatory markers and improvement in clinical status with early initiation of adjunctive IV anakinra. CONCLUSIONS In this case series, adult cHIS criteria were successfully used to identify pediatric COVID-19 patients with hyperinflammation. Ferritin levels decreased following early initiation of IV anakinra.

Extracorporeal Membrane Oxygenation in Children With COVID-19: A Systematic Review and Meta-Analysis*

“…The European Extracorporeal Life Support Organization (ELSO) prospective survey highlighted that ECMO use for COVID-19 in children is infrequent (8)(9)(10). Although various complications, including pneumothorax, gastrointestinal bleeding, and stroke, have been identified, the overall frequency is unknown (8,(10)(11)(12). Furthermore, reported mortality in children who required ECMO for severe COVID-19-related illnesses also varies due to the small sample size in each study (8,9,11,13,14).…”

Intravenous anakinra for the treatment of haemophagocytic lymphohistiocytosis/macrophage activation syndrome: A systematic review

“…Two patients were recorded with both infectious and rheumatological triggers, a 22‐month‐old male with septic arthritis and a subsequent diagnosis of JIA, 39 and an adult with group A streptococcal infection and inflammatory arthritis 44 . Whilst some COVID‐19 patients had rheumatological and oncological co‐morbidities, which may have contributed to sHLH/MAS susceptability, the underlying trigger was felt to be COVID‐19 in all cases 53,59 . Of the n = 4 ‘other’ triggers, these were an adult post‐liver transplant for non‐alcoholic steatohepatitis cirrhosis, 21 a 9‐year‐old with cytokine‐release syndrome driven by chimeric antigen receptor T‐cell therapy, 50 an adult with retained products of conception 44 and an adult with post‐transplant‐related lymphoproliferative disorder 44 .…”

“…One patient (3.7%) had HLH and cytokine‐release syndrome secondary to chimeric antigen receptor T‐cell therapy. No paediatric patient had HLH attributed to an oncological trigger per se, although four patients had concurrent/historical cancer diagnoses (B‐precursor acute myeloid leukaemia, two with neuroblastoma and Hodgkin lymphoma) 43,50,51,59 . The patients with neuroblastoma and Hodgkin lymphoma had significant infection (Table 1).…”

“…44 Whilst some COVID-19 patients had rheumatological and oncological co-morbidities, which may have contributed to sHLH/MAS susceptability, the underlying trigger was felt to be COVID-19 in all cases. 53,59 Of the n = 4 'other' triggers, these were an adult post-liver transplant for non-alcoholic steatohepatitis cirrhosis, 21 a 9-year-old with cytokine-release syndrome driven by chimeric antigen receptor T-cell therapy, 50 an adult with retained products of conception 44 and an adult with post-transplant-related lymphoproliferative disorder. 44 The sHLH triggers differed between paediatric and adult patients, with half of paediatric patients (<18 years) having a rheumatological diagnosis (48%) (Figure 2B), 25% being associated with severe or disseminated infection, and 18.5% having no known trigger.…”

“…No paediatric patient had HLH attributed to an oncological trigger per se, although four patients had concurrent/historical cancer diagnoses (B-precursor acute myeloid leukaemia, two with neuroblastoma and Hodgkin lymphoma). 43,50,51,59 The patients with neuroblastoma and Hodgkin lymphoma had significant infection (Table 1). Unfortunately, two studies did not report on underlying sHLH/MAS triggers, accounting for eight paediatric patients in total.…”