Discussion
The objective of this study was to describe the clinical presentation of COVID-19 in the pediatric oncology and hematology population, not to determine the incidence of COVID-19. Indeed, each center may have different screening strategies and the data collected in this study do not allow for the calculation of the incidence of COVID-19. Our data shows that clinical and radiological descriptions of COVID-19 are quite similar to those reported in adults, and that incubation period or virus clearance appear to be the same in this population as what has been described before. Most of patients developed a mild or even an asymptomatic form of the disease. However, as we previously stated[11] and in contrast with other reports[4–6], we found that patients may be at a higher risk of developing a severe form of COVID-19. Indeed, five patients (15%) required admission in an intensive care unit (ICU) and one patient died from COVID-19 complications. Among patients with a cancer history, one had high-grade glioma, the others had a relapsed acute lymphoblastic leukemia (ALL) and were highly immunocompromised. The deceased patient was a four-year-old boy undergoing induction chemotherapy for relapsed ALL. His respiratory state worsened and he was admitted in an ICU, where he developed intense macrophage activation syndrome and subsequent complications that led to his death. In the study from Boulad et al., only one patient required a noncritical care hospitalization and the COVID-19 manifestations were mild for most patients[4]. This is concordant with the data from Spain where no severe case was reported[5]. In contrast, in New York, the joint experience form the memorial Sloan Kettering Cancer Center and New York Presbyterian Hospital  shows that among 19 patients infected with SARS-CoV-2, five (20%) required intensive care including mechanical ventilation and a 12-year-old boy with hemoglobinopathy developed acute chest syndrome and died from COVID-19 complications. In Lombardia, Ferrari and al. reported COVID-19 complications in 2/21 patients[12]. We have no clear explanation for such differences between our work and these reports and it may be only due to happenstance. Indeed, ICU admission criteria are likely similar in France and other Western countries and there is no reason that French patients may be more immunocompromised or vulnerable than their US, Spanish or Italian counterparts. In adults, recent reports suggest that patients currently treated for a cancer or with a history of cancer more frequently develop severe COVID-19 compared to general population[2, 13, 14].
Oncologic treatment was delayed in almost half of cases, which indicates that COVID-19 impacted care of patients even if most cases were mild. Of note, some patients had their treatment as planned and did not develop any complication. However, every situation is unique and clinicians who followed these patients made their decision regarding patients’ own history and potent risk factors, so that no general recommendation to pursue oncologic treatment may be stated from this study. On the contrary, delaying a non-urgent oncologic treatment appears to be wise in the context of suspected or proven infection, as suggested by most clinicians (in press). Oppositely, delaying the initial management of children with cancer may be dramatic. Thus, in Phildelphia, Ding et al. reported 5 patients who became critically hill because of delay in diagnosis illustrating indirect impact on morbidity of COVID-19[7].
A striking difference between our data and the first published reports is the sex ratio[4, 5]. Though there were slightly more females than males in our study, our cohort is equilibrated regarding sex distribution. In some reports concerning pediatric oncology populations, there was a strong proportion of males with 5 to 15 times more male than female[4, 5]. Similarly, Gampel and al. reported that among the 5 patients requiring intensive care, all mere males[15]. Other studies in pediatric general population[16] or adult oncology population[2] did not found this high proportion of males. Thus, we cannot explain the difference between our study and the work from Boulad et al. and de Rojas et al. but there is currently no clue for a specific sex distribution among children and/or oncology patients.
Biological findings are difficult to interpret since a high proportion of patients recently received drugs that could alter blood tests. However, profound neutropenia and profound lymphopenia were found in almost one third of patients. Even if that can be explained by the oncologic treatment received, the infection likely participated and increased the cytopenias. Lymphopenia is common with SARS-CoV-2 infection, and it appears that the deeper the lymphopenia, the more severe the disease[17, 18]. Our cohort is too small to address this question even if two of the five patients admitted in an ICU had profound lymphopenia. For the same reason, it is not possible to draw a conclusion on the association between PCR level and disease severity. However, it should be noted that CRP level was quite low in our cohort and that of the four patients with elevated CRP level above 50 mg/L, two were admitted to an ICU.
Clinicians should pay attention to lung lesions caused by COVID-19 for patients who may receive treatments that could themselves damage lung tissue. Indeed, delaying lung irradiation or administration of drugs with known lung toxicity may be considered for infected patients. However, this delay should not be too long to avoid the risk of progression. In our cohort, the mean delay in treatment administration was 14 days, which appears reasonable regarding both this risk of disease progression and the risk of complications related to COVID-19.
Until we get more data, we advocate not to reassure parents regarding the mild forms of COVID-19 in patients treated for malignancies. We recommend that patients with severe hematological malignancies and/or receiving heavily immunosuppressive treatments should be carefully watched and protected from the COVID-19 risk. This shall be of interest for patients in South Asia and Latin America who are now facing the COVID-19 pandemic.