Active COVID-19 Clinical Pathway – All Settings – High-Risk Conditions

Active COVID-19 Clinical Pathway – All Settings

High-Risk Conditions

Pediatric data informing risk stratification are limited.

The table below summarizes conditions most consistently associated with an increased risk of severe COVID-19 in children.

Moderate-Severe Immunocompromise

Considered higher risk regardless of vaccination status.

Category Examples
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
HIV
With CD4 count < 5% or < 200/mm3 or history of AIDS-defining illness without immune reconstitution		 N/A
Malignancy or Histiocytic Disorders
e.g., HLH, LCH
  • Multi-agent chemotherapy within 3 mos
  • B-cell depleting agent within 6 mos
    • e.g., rituximab, ocrelizumab, ofatumumab, blinatumomab, inotuzumab, daratumumab, alemtuzumab
  • Any CAR-T cell therapy
Non-Malignant Hematologic Disorders
  • Severe aplastic anemia s/p ATG within 3 mos
  • Auto-immune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP) post anti-CD20/52 or anti-CD38 within 6 mos
    • e.g., rituximab, ocrelizumab, ofatumumab, daratumumab, alemtuzumab
  • 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 mos) or alemtuzumab (< 6 mos)
  • ALC < 200/µL
  • GvHD requiring systemic immunosuppression within 6 mos
  • IVIG replacement within the past 6 mos
Solid Organ Transplant
  • Lung transplant recipients within 1 yr of transplant
  • Non-lung SOT within 6 mos 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 mos) or alemtuzumab (< 6 mos)
    • Immunosuppressive treatment for transplant rejection within 3 mos
    • Steroids
      • > 20 mg/day methylprednisolone equivalents for > 2 wks
Immunosuppressive Medications
  • Receiving an immunomodulator that significantly impacts B or T cell number or function, including but not limited to:
    • ATG, < 3 mos
    • 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 wks
    • Multi-agent/cytotoxic cancer chemotherapy within 3 mos
  • Multi-agent immune suppression, including patients receiving two or more drugs such as but not limited to:
    • Abatacept (Orencia)
    • Adalimumab (Humira)
    • Anakinra (Kineret)
    • Azathioprine (Imuran)
    • Baricitinib (Olumiant)
    • Belimumab (Benlysta)
    • Bortezomib (Velcade)
    • Canakinumab (Ilaris)
    • Cyclosporine
    • Eculizumab (Solaris)
    • Emapalumab (Gamifant)
    • Etanercept (Enbrel)
    • Golimumab (Simponi)
    • Hydroxyurea (Droxia, Hydrea, hydroxycarbamide)
    • Ixekizumab (Taltz)
    • Leflunomide (Arava)
    • Methotrexate (Trexall, Otrexup, Xatmep, Rasuvo)
    • Mycophenolate acid (Myfortic)
    • Mycophenolate mofetil (Cellcept)
    • Ruxolitinib (Jakafi)
    • Secukinumab (Cosentyx)
    • Sirolimus (Rapamycin)
    • Tacrolimus (Prograf)
    • Tofacitinib (Xeljanz)
    • Tocilizumab (Actemra)
    • Upadacitinib (Rinvoq)
    • Ustekinumab (Stelara)
    • Vedolizumab (Entyvio)

Other Comorbid Conditions Associated with Severe Disease

Presence of multiple comorbidities and/or not up to date on COVID-19 vaccines increases risk and should lower the threshold for antiviral treatment.

Sickle Cell Disease
  • All patients with sickle cell disease ≥ 21 yrs of age
  • Patients with SCD < 21 yrs of age and a history of frequent VOE admissions > 2 times in the last 3 yrs, any ACS in the past 3 yrs, 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
  • Respiratory technology dependence
  • Severe asthma treated with biologics or systemic immunosuppression
Neurodevelopmental Disease Neuromuscular disorder or other congenital/genetic disorder that impairs the ability to clear secretions from the upper airway due to an ineffective cough
Obesity (BMI ≥ 30 or > 95th percentile for age) Risk associated with obesity is greatest for adolescents ≥ 12 yrs old, association in younger children is less clear
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%
Diabetes Poorly controlled (e.g., A1C > 10) type II diabetes, or type I diabetes with concurrent obesity (BMI ≥ 30 or >95th percentile for age) or concomitant lung disease