Table 3 Proposal of integration of the risk categories identified by AIFA for the administration of mAbs in subjects aged 12 to 17 years

Patients aged ≥12 years old, who tested positive for SARS-CoV-2, with mild-moderate disease, a recent onset (less than 10 days, except for patients with immunodeficiency and persistently positive molecular test but negative serologic test)* and the presence of risk factors for severe disease:

a. BMI ≥ 95° percentile for age and gender (WHO Tables)

b. Haemoglobinopathy (sickle cell anemia and thalassemia major or intermedia)

c. Hereditary or acquired thrombophilia

d. Onco-hematological patients with lymphopenia (< 300/mmc), neutropenia (< 500/mmc), high intensity treatment (AML, induction and reinduction phase for those with ALA, NHL, hematopoietic stem cell transplant recipients (< 30 days if autologous or < 100 days if allogenic)

e. Solid organ or hematopoietic stem cells transplant recipients

f. Congenital or acquired hearth diseases: single ventricle physiology or status post Fontan intervention (total cavo-pulmonary connection), severe heart valve disease, chronic cyanosis (SpO2 < 85%), severe ventricular dysfunction, therapy-dependent cardiomyopathies, pulmonary hypertension on treatment.

g. Chronic obstructive or restrictive lung disease requiring daily therapy or biologics (e.g. severe or uncontrolled asthma dependent on specific monoclonal antibody therapy or oral steroids for symptoms control); cystic fibrosis with moderate to severe respiratory impairment, reduced BMI, transplant recipients or with other significative comorbidities; pulmonary fibrosis; bronchiolitis obliterans; bronchopulmonary dysplasia; chronic pulmonary GVHD

h. Dependence on technological device (e.g. subjects with tracheostomy and/or gastrostomy)

i. Inflammatory Bowel Diseases (IBDs) on immunosuppressant therapy

j. PIDs at high risk for progression to severe disease (Table 2); case by case approach for those with mild-moderate risk PIDs

k. Secondary Immunodeficiencies including HIV with low lymphocyte count (CD4+ lymphocytes < 15% or < 200/mmc) or with severe comorbidities, chemotherapy (< 6 months from suspension), hematopoietic stem cells transplant (< 3 months if autologous, < 6 months if allogenic or in presence of chronic active GVHD) or solid organ transplant and protracted immunosuppressant therapies

l. Uncontrolled Diabetes mellitus (HbA1c > 9% or 75 mmol/mol) or with chronic complications

m. Chronic renal failure requiring hemodialysis or peritoneal dialysis

n. Neurological or neuro-muscular diseases with at least one of the following:

- Respiratory muscles dysfunction with FVC < 60% (especially if associated with kyphoscoliosis)

- Impaired cough and reduced respiratory clearance

- Hearth involvement

- Metabolic conditions or impairment of the neuromuscular junctions at risk of deterioration in case of fever, fasting or infection

- Conditions at risk for rhabdomyolysis in case of fever, fasting or infection

- Chronic immunosuppressant or corticosteroid therapies

*Bamlanivimab+Etesevimab is approved for outpatients (not-hospitalized patients) without supplemental oxygen therapy for COVID 19; Casirivimab+Imdevimab is approved also for hospitalized patients and for patients with conventional oxygen therapy (excluding high flow and mechanical ventilation)