Discussion
Many studies demonstrated that majority of symptomatic cases in children were described as mild and children were less likely to develop severe illness than adults [3]. Several reports suggested that patients with cancer might be at increased risk of developing COVID-19 [4]. However, the knowledge of relationship between children with cancer and COVID is still limited. In this study, we reported a boy developed B-ALL with recent SARS-CoV-2 infection. His atypical clinical manifestation was different from B-ALL. We speculated the proliferation of lymphoblasts might be caused by SARS-CoV-2 infection temporarily until laboratory findings confirmed B-ALL.
Does SARS-CoV-2 infection have an impact on the development of childhood ALL? Due to lack of literature, there are sporadic reports about COVID-19 concurrent in newly diagnosed ALL [5,6] or during maintenance therapy [7], or reactivation with pre-existing ALL [8] in children. Different from above, our case is one of the few cases developed ALL following SARS-CoV-2 infection so far as we know [9,10]. Leclercq et al reported an 8-year-old Caucasian boy with an extensive maculopapular rash and pancytopenia with recent SARS-CoV-2 and EBV infections and early stage B-ALL [9].
SARS-CoV-2 infections might be related to the immune response including cellular and humoral immune [11,12]. In our report, significant higher proportion of Treg, DNT and TFH cells was observed, which indicated immune dysregulation might play a role in this patient. It was widely spread a hypothesis that ALL arised by “two-hits” [13,14]. The “first-hit” occurred prenatally with a leukemia- associated genetic change. A subsequent “second-hit” occurring postnatally in a population of preleukemia clone would lead to the proliferation of leukemia cells. So-called “second-hit”, is postulated to be exposure to a common infectious agent (eg, virus) in a susceptible child who was under an abnormal or over- stimulated immune response. In the present study, given the child case who developed B-cell ALL following a SARS-CoV-2 infection, with immune abnormalities, we make a scientific hypothesis: the potential possibility of infection with SARS-CoV-2, could exacerbate the patient’s immuno-compromised state and induce an immune response that could allow pre-leukemia cell clone proliferate to facilitate the development of pediatric ALL. It is possible that the infection of predisposed children by COVID-19 act as a “second-hit”, leading to a driving force of developing ALL.
In conclusion, we reported a rare child case who developed B-cell ALL following a SARS-CoV-2 infection. Whether COVID-19 infection being the “second” leukemogenic hit in childhood ALL, need to answer in the future. Further studies are needed to enlarge the case number to explore the potential oncogenic effects of SARS-CoV-2 in children.