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.