Results
During the month of March, a total of 315 children were tested in our hospital for SARS-CoV-2 and 51 were positive (16%). Twenty-eight of the positive cases (55%) were admitted. A total of 8 positive cases (15%) were immunosuppressed patients, and 3 were followed as outpatients. The underlying pathology was hemato-oncological in most cases (three patients had undergone a hematopoietic stem cell transplant), two patients had undergone a liver or a kidney transplant, and the last case was a girl on chronic hemodialysis with a vasculitis receiving immunosuppressive treatment. The median age was 12.6 years (interquartile range: IQR 9.5–12.6). All the patients had been on immunosuppressive treatment with a median duration of 24 months (IQR 12–93). All had respiratory symptoms, 5 of them had fever, and the majority had slight radiological alterations (only two had focal infiltrates). In only one case the chest X-ray worsened during hospitalization. One patient needed oxygen therapy and one case had diarrhea. None of them had anosmia or ageusia. One patient developed a hemophagocytic lymphohistiocytosis-like syndrome (sHLH), with persistent fever, cytopenias, low fibrinogen and elevated triglycerides, and elevated ferritin, and required specific treatment with dexamethasone, as per the HLH-2004 protocol. Antiviral treatment was initiated according to our National guidelines, developed by the National Infectious Disease Society (SEIP), in coordination with the National Pediatric Intensive Care Society (SECIP) and the National Pediatric Association (AEP) available at https://www.aeped.es/noticias/documento-manejo-clinico-paciente-pediatrico-y-pacientes-riesgo-con-infeccion-por-sars-cov2. Hydroxychloroquine was initiated upon diagnosis (positive PCR for SARS-CoV-2) when there were signs/ symptoms of moderate-severe disease (respiratory signs, pneumonia on chest X ray, blood parameters of severity such as lymphopenia or elevated CRP, D-dimer or Il-6). Remdesivir was requested, under compassionate use, in the most severe cases. Following theses guidelines, in 5/8 cases, some antiviral treatment was prescribed, with hydroxychloroquine being the most frequent. Two patients received remdesivir (the two oncological patients who required admission: patient 1 who had oxygen requirement and patient 4 who had persistent symptoms with severe lymphopenia and elevated inflammatory parameters) and only one patient received tocilizumab due to persistent fever and elevated IL-6. There were no significant toxicities following the treatments received. Immunosuppressive therapy was decreased or withdrawn in 6 patients (the other two had been off immunosuppression for 1 and 2 months, respectively). All but one case developed progressive lymphopenia. D-dimer was moderately elevated. With a median follow up of 106 days (IQR 103–113) from COVID-19 diagnosis, no child required admission to the pediatric intensive care unit or died. At present, all the patients are being followed up as outpatients and have had no further complications related to COVID-19. The clinical characteristics of the patients, as well as details on the treatment received, are outlined in Table 1.
Table 1 Clinical characteristics of immunocompromised children with COVID-19 disease
Case # 1 2 3 4 5 6 7 8
Age (years) 15 13 12.6 9 6.7 11 12.6 14.8
Gender F M M M M M F M
Primary disease HSCT
PID (CTLA4 deficiency) HSCT
Myelodysplastic syndrome HSCT
B-ALL T-ALL Melanoma Liver Tx C-ANCA vasculitis.
Hemodialysis Kidney Tx
Immunosuppressive treatment/targeted therapy None (stopped for 1 month). CD4 cells: 216/ μL Ruxolitinib None (stopped for 2 months). CD4 cells: 30/ μL Oral mercaptopurine and methotrexate Trametinib Prednisone, tacrolimus Prednisone, azathioprine Prednisone, tacrolimus, mycophenolate (MMF)
Fever Yes No Yes Yes No Yes Yes No
Cough No No No Yes Yes Yes Yes Yes
Sore throat No Yes No No No No Yes No
Dyspnea Yes No No No No No No No
Lymphocytes/mm3
(minimum value) 730 1210 520 340 2730 970 380 1620
D-dimer ng/mL
(maximum value) 301 - 418 1143 370 - 1168 -
IL-6 pg/mL (maximum value) 9.60 2.30 - 192 - - - -
C- Reactive Protein (mg/L) 26.2 1.9 18.9 24.6 0.6 0.9 9 106
Ferritin (mg/dl) Not done Not done 622 1534 Not done Not done 1270 553
Chest X-ray Normal
(Previous
lobectomy) Interstitial infiltrate Interstitial infiltrate Interstitial infiltrate Focal infiltrate Mild parahilar infiltrates Normal initially but focal infiltrate on evolution Focal infiltrate
Required hospitalization Yes No No Yes No Yes Yes Yes
Treatment HCQ*
Remdesivir** IS withdrawal HCQ* IS withdrawal
HCQ*
Remdesivir**
Tocilizumab
Dexamethasone*** Trametinib withdrawal Reduction in IS (50% tacrolimus reduction) Reduction in IS (azathioprine withdrawal)
LPV/Rtv
HCQ* Reduction in IS (MMF withdrawal, tacrolimus decrease and prednisone increase)
HCQ*
Duration of stay (days) 11 - - 28 - 3 4 2
Complications O2 requirement on nasal cannula (maximun 2 lpm) None None HLH-like syndrome None None None None
F female, M male, HSCT: hematopoietic stem cell transplant, PID primary immunodeficiency, B-ALL: B cell acute lymphoblastic leukemia, T-ALL T cell acute lymphoblastic leukemia, Tx transplant, HCQ hydroxychloroquine, IS immunosuppressors, LPV/Rtv lopinavir/ritonavir, O2 oxygen; HLH hemophagocytic lymphohistiocytosis. MMF mycophenolate
*HCQ was initiated in patients 1, 3, 4, and 8 once confirmation of positive SARS-CoV-2 with a nasal swab was obtained (< 24 h from consultation at our hospital). Patients 1, 3, and 8 attended the Emergency Department in the first 24 h after onset of symptoms. Patient 4 had fever of 4 days when the nasal swab was obtained, and patient 7 received 5 days of LPV/Rtv initially and due to persistent symptoms was switched to HCQ. According to our guidelines, the oral dose was as follows: HCQ 6.5 mg/kg/day (dosing q12 h) in 6 year-olds, and HCQ 10 mg/kg/day (dosing q12 h) in children > 6 years (maximum daily dose 400 mg) for 5 days
**Remdesivir was given for a total of 7 days on patient 1 and 10 days on patient 4, at an intravenous dose of 5 mg/kg on day 1, followed by a maintenance dose of 2.5 mg/kg from days 2 to 9 (patients <40 kg) or 200 mg/iv on day 1 followed by 100 mg/iv on days 2-9 (for patients >40 kg)
***Dexamethasone was given as per the HLH 2004 trial, although with a shorter duration: 10 mg/m2/day for 7 days, followed by 5 mg/m2/day for another 7 days, followed by 2.5 mg/m2 for 7 days and 1.25 mg/m2 for 2 days and then a tapering dose with hydrocortisone