Active COVID-19, Clinical Pathway — All Settings

High Risk Conditions

Pediatric data informing risk stratification to identify children at highest risk of severe disease are limited. The table below summarizes pediatric patients who appear at highest risk for severe disease, particularly if they are unvaccinated or not expected to develop protective immunity from SARS-CoV-2 vaccination due to an immunocompromising condition. We recommend prioritizing these patients for use of COVID-19 therapies.

High Comorbid Risk Criteria
Immunocompromising Conditions or Medications — Patients in these categories
are considered “high risk” regardless of vaccination status.
Category Specific CHOP Criteria
Primary Immunodeficiency
  • Severe combined immunodeficiency
  • Innate immune defects
  • Significant T-cell deficiency or dysfunction (e.g., patients with prior opportunistic infections)
  • Genetic mutations resulting in complete loss of B cells and/or IgG production
  • Severe hypogammaglobulinemia requiring routine IVIG replacement
  • Auto-immune polyendocrinopathy candidiasis ectodermal dystrophy (APECED)
  • CD4 count < 5% or < 200/mm3 or history of AIDS defining illness without immune reconstitution
  • Active malignancy receiving multiagent chemotherapy within 3 months
  • Histiocytic disorders (e.g., HLH, LCH, etc.) receiving multiagent chemotherapy within 3 months
  • Active malignancy receiving B-cell depleting agent within 6 months (e.g., rituximab, ocrelizumab, ofatumumab, blinatumomab, inotuzumab, daratumumab, alemtumumab)
  • CAR-T cell therapy
Non-malignant Hematologic Disorders
  • Severe aplastic anemia s/p ATG within 3 months
  • Auto-immune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP) post anti-CD20/52 or anti-CD38 within 6 months (e.g., rituximab, ocrelizumab, ofatumumab, daratumumab, alemtumumab)
  • Congenital BMF with combined neutropenia and lymphopenia
Hematopoietic Stem Cell Transplant
  • < 100 days post-allogeneic HCT
  • < 30 days post-autologous HCT
  • Anti-lymphocyte therapy (e.g., ATG < 3 months or alemtuzumab < 6 months)
  • ALC < 200/ul
  • GvHD requiring systemic immunosuppression within 6 months
  • IVIG replacement within the past 6 months
Solid Organ Transplant
  • Lung transplant recipients within 1 year of transplant
  • Non-lung SOT within 6 months of transplant
  • High-level immunosuppression (e.g., treatment of rejection) – specific definitions vary by organ type and include but are not limited to:
    • Treatment with ATG (< 3 months) or alemtuzumab (< 6 months)
    • Immunosuppressive treatment for transplant rejection within 3 months
    • Steroids (> 20 mg/day methylprednisolone equivalents for > 2 weeks)
Immunosuppressive Medications
  • Receiving an immunomodulator that significantly impacts B or T cell number or function, including but not limited to:
    • ATG (< 3 months)
    • Anti-CD19, CD20, CD22, CD38, or CD52 (e.g., rituximab, ocrelizumab, ofatumumab, blinatumomab, inotuzumab, daratumumab alemtuzumab)
    • TNF-α inhibitors
    • Anti-cytokine (e.g., tocilizumab, ustekinumab)
    • Steroids (> 20 mg/day methylprednisolone equivalents for > 2 weeks)
    • Multiagent/cytotoxic cancer chemotherapy within 3 months
    • Multi-agent immune suppression, including patients receiving two or more drugs such as (but not limited to): azathioprine (Imuran), mycophenolate mofetil (Cellcept), mycophenolic acid (Myfortic), leflunomide (Arava), etanercept (Enbrel), adalimumab (Humira), golimumab (Simponi), infliximab (Remicade), tocilizumab (Actemra), ustekinumab (Stelara), secukinumab (Cosentyx), vedolizumab (Entyvio), anakinra (Kineret), canakinumab (Ilaris), belimumab (Benlysta), tacrolimus (Prograf), methotrexate (Trexall, Otrexup, Xatmep, Rasuvo), tofacitinib (Xeljanz), upadacitinib (Rinvoq), baricitinib (Olumiant), ruxolitinib (Jakafi), abatacept (Orecia), ixekizumab (Taltz), eculizumab (Solaris), bortezomib (Velcade), hydroxyurea (Droxia, Hydrea, hydroxycarbamide), emapalumab (Gamifant), cyclosporine, sirolimus (Rapamycin), inhibitors).
Other High-risk Conditions
Patients with these conditions are considered highest risk if they are not fully vaccinated.1
Category Specific CHOP Criteria
Sickle Cell Disease
  • All patients with sickle cell disease ≥ 21 years of age
  • Patients with SCD < 21 years of age and a history of frequent VOE admissions (> 2 times in the last 3 years), any ACS (in the past three years), or concurrent pulmonary hypertension, renal or cardiac disease
  • All hospitalized sickle cell disease patients admitted with a new diagnosis of acute chest syndrome in the setting of acute COVID-19
Severe Pulmonary Disease
  • End stage lung disease requiring a daily medication (“end stage” defined as FEV < 30% of predicted) or listed for lung transplant
  • Medical complexity with respiratory technology dependence or neuromuscular disorder or other congenital anomaly that impairs the ability to clear secretions from the upper airway due to an ineffective cough
  • Severe asthma (treated with biologics or systemic immunosuppression)
  • BMI ≥ 30 (> 18 years old) or > 95th percentile for age (< 18 years old)
Severe Cardiac Disease
  • Severe pulmonary hypertension (receiving medical therapy e.g., remodulin)
  • Cardiomyopathy or congenital heart disease with severely diminished systolic function (LVSF < 35%) or receiving home inotropic therapy or VAD support
  • Repaired or unrepaired cyanotic congenital heart disease with baseline oxygen saturation < 85%
  • Poorly controlled (e.g., A1C > 10) type II diabetes or type I diabetes with concurrent obesity (BMI > 95th percentile) or concomitant lung disease
  • 1 Fully vaccinated is defined as an immunocompetent patient > 14 days after the second dose of either mRNA vaccine against COVID-19 OR a single dose of the Johnson and Johnson vaccine