Table 7.

Hyperinflammation in COVID-19^*

Guidance statement	Level of consensus
Medically complex children and those receiving immunosuppressive medications, including moderate-to- high-dose glucocorticoids, may be at higher risk for severe outcomes in COVID-19.	Moderate to high
Children and adults admitted to the hospital with COVID-19 present with similar symptoms, including fever, upper respiratory tract symptoms, abdominal pain, and diarrhea.	Moderate
Children with severe respiratory symptoms due to COVID-19 with any of the following should be considered for immunomodulatory therapy: ARDS, shock/cardiac dysfunction, substantial elevation in LDH, D-dimer, IL-6, IL-2R, CRP, and/or ferritin level, and depressed lymphocyte count, albumin level, and/ or platelet count.	Moderate to high
Glucocorticoids should be used as first-tier immunomodulatory treatment in patients with COVID-19 and hyperinflammation.	High
Anakinra appears safe in severe infections and in children with hyperinflammatory syndromes. In children with COVID-19 and hyperinflammation, anakinra (>4 mg/kg/day IV or SC) should be considered for immunomodulatory therapy in patients with refractory disease despite glucocorticoid treatment or in patients with contraindications to steroids. Initiation of anakinra before invasive mechanical ventilation may be beneficial.	High
Children with COVID-19 treated with anakinra should be monitored for LFT abnormalities.	Moderate
Tocilizumab is not recommended for a majority of pediatric patients with COVID-19 and hyperinflammation, given the lack of benefit reported in randomized, double-blind, placebo-controlled trials in adults with COVID-19 pneumonia. In addition, the effects of tocilizumab are long-lasting, which leaves little recourse if a patient does not respond favorably to the medication.	Moderate to high
There is insufficient evidence to support the use of other immunomodulatory agents unless glucocorticoids and IL-1-blocking therapies are contraindicated or have failed.	Moderate

^*COVID-19 = coronavirus disease 2019; ARDS = acute respiratory distress syndrome; LDH = lactate dehydrogenase; IL-6 = interleukin-6; IL-2R = interleukin-2 receptor; CRP = C-reactive protein; IV = intravenous; SC = subcutaneous; LFT = liver function test.