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)
HIV	CD4 count < 5% or < 200/mm³ or history of AIDS defining illness without immune reconstitution
Malignancy	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)
Obesity	BMI ≥ 30 (> 18 years old) or > 95^th 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%
Diabetes	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

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The clinical pathways are based upon publicly available medical evidence and/or a consensus of medical practitioners at The Children’s Hospital of Philadelphia (“CHOP”) and are current at the time of publication. These clinical pathways are intended to be a guide for practitioners and may need to be adapted for each specific patient based on the practitioner’s professional judgment, consideration of any unique circumstances, the needs of each patient and their family, and/or the availability of various resources at the health care institution where the patient is located.

Accordingly, these clinical pathways are not intended to constitute medical advice or treatment, or to create a doctor-patient relationship between/among The Children’s Hospital of Philadelphia (“CHOP”), its physicians and the individual patients in question. CHOP does not represent or warrant that the clinical pathways are in every respect accurate or complete, or that one or more of them apply to a particular patient or medical condition. CHOP is not responsible for any errors or omissions in the clinical pathways, or for any outcomes a patient might experience where a clinician consulted one or more such pathways in connection with providing care for that patient.