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.