Results
Information of SARS-CoV-2 positive cases was received from 41 hospitals. According to the Spanish Pediatric Cancer Registry (RETI-SEHOP), these centers are responsible for the treatment of 97.6% of pediatric cancer patients in Spain. As to non-malignant hematological cases, no global database is available due to the heterogeneity of the different diseases, but the sample seems to be representative because these chronic diseases are treated in the same Pediatric and Oncology Units.
Demographic data, underlying diagnosis, clinical features, therapy received and outcome related to RT-PCR confirmed SARS-CoV-2 (nasopharyngeal swab) infection of 47 patients are summarized inTable 1 . The median age of our cohort was 8.2 years, with male predominance (72.3%). The majority of cases had leukemia or lymphoma (51.5%), followed by patients with solid tumors (29.8%) as underlying condition. Seventeen percent of the patients (n=8) had undergone an allo-stem-cell transplantation (SCT); five of these secondary to hematological diseases and the rest of them due to severe primary immunodeficiencies. Six patients with severe non-oncologic hematologic conditions under immunosuppressive therapy were included in the study. Three of 47 patients had received CAR T-cell therapy as salvage regimen for relapsed B-ALL. Regarding clinical impact, the majority of patients were asymptomatic (25.5%) or had only mild symptoms (51.1%). Fever was the most frequent symptom at presentation (51.1%), followed by cough and rhinorrhea (40.4%). A minority of cases presented diarrhea (4.2%) and only two patients presented some type of cutaneous manifestation (1 case with rash, 1 case with purpuric lesions). Radiologic abnormalities (mostly by chest-X-ray, 3 CT scans performed in critical patients) consisting in pneumonia were observed in 32.4% of the patients. The percentage of children who required hospitalization was 76.6% (n=32). However, 12 of them were already admitted when COVID-19 diagnosis was made: One due to febrile neutropenia, five for cancer treatment, 2 post-SCT, 4 not reported). Severe illness with respiratory distress and/or hypoxemia was identified in 11 patients. Four of them, all males, evolved to critical illness with progressive respiratory failure requiring admission to the PICU (8.5% of all patients).
The clinical course of the 4 critically-ill COVID-19 patients is summarized below:
Case 1: A 16-year-old male undergoing myelosuppressive chemotherapy for primary mediastinal large B-cell lymphoma admitted initially for severe neutropenia and pancreatitis. He developed pneumonia requiring cannula oxygen therapy; recovering soon after. Case 2 was an 8-year-old boy admitted post-SCT due to a primary immunodeficiency with graft-versus-host disease (GVHD), who presented with bilateral pneumonia requiring mechanical ventilation and ECMO. The patient presented a torpid clinical evolution and deceased. Case 3, 18 year-old male on therapy for an Ewing-like round cell sarcoma, with initial fever and cough. Thereafter he developed respiratory worsening with new bilateral infiltrates and respiratory failure, needing high flow oxygen therapy, with a favorable clinical outcome. Case 4 was an 11-year-old boy, diagnosed with relapsed B-ALL in third complete remission after CART cell therapy followed by unrelated allo-SCT. At the time of COVID-19 diagnosis, 15 months after allo-SCT, he presented an extensive chronic GVHD and poor engraftment that required several immunosuppressors. He presented initially with fever, cough, and unilateral pneumonia. Few days later developed dyspnea and hypoxemia, requiring increasing respiratory support with non-invasive ventilation and mechanical ventilation. He also developed secondary HLH, with altered coagulation, hypertriglyceridemia, hypoalbuminemia, and ferritin levels that raised up to 124 000 ug/L (NR 10-120ug/L). Moreover, D-Dimer and IL-6 raised up to 2.02 mg/dL (NR <0,5mg/dl) and 394 pg/mL (NR < 5pg/ml), respectively. Finally, the patient died secondary to a pulmonary hemorrhage and multiorgan failure. Regarding relevant abnormal laboratory findings, critically ill patients presented in a higher frequency with severe lymphopenia (medians: 85 vs 1000, p=0.0034) and higher ferritin levels at the onset of symptoms (medians: 6666.5 ng/ml vs 1037 ng/ml, p=0.027). The maximum ferritin level was also significantly superior in critical patients admitted to the PICU in comparison to the other cases (medians: 23 077 ng/ml vs 1507.5 ng/ml, p<0.001). No statistically significant differences were observed in the absolute number of neutrophils and LDH. The time from clinical onset to first negative RT-PCR results was not available for all patients, but in some of them, RT-PCR remained positive after 7 weeks. Asymptomatic/mild cases (44.6%) did not received any therapy. Twenty-three patients received hydroxychloroquine (9 patients combined with azithromycin), followed by antivirals (19.1%) and corticosteroids (6.4%). Six patients received monoclonal antibodies against IL1/IL6. Anti-cancer therapy was interrupted in 57.9% of the cases. Prophylactic anticoagulation was administered to five patients (10.6%) with no thromboembolic events diagnosed. Outcome was overall good, with most symptomatic patients recovering back to baseline clinical situation. Two deaths were reported in the post allo-SCT subgroup.