COVID‐19 and childhood acute lymphoblastic leukemia
Mel Greaves
Abstract
To the Editor: The suggestion of Taub and colleagues1 that the current SARS-coV-2 pandemic might have important implications for the incidence of childhood acute lymphoblastic leukemia (ALL) is cogent and opportune. There are indeed two contrasting predictions based on the etiological model referred to.2 First, widespread exposure of children to SARS-CoV-2, even with no or mild symptoms, could provide the crucial second hit that promotes clonal evolution and clinical emergence of ALL. Prior observations with other respiratory virus epidemics or pandemics support this contention. A report from the UK documented that spikes in ALL incidence followed some months after epidemics of seasonal flu.3 During the 2009/2010 AH1N1 swine flu pandemic, a significant space/time cluster of virus-associated cases was detected in Milan around 2-3 months after the peak infection rate in Italy.4 The timing of these associations indicates that any causal involvement of the viral infection would have to be as a proximal or promotional trigger. Something similar might therefore be anticipated with SARS-coV-2. Second, and in contrast, the widespread closure of nurseries and schools in addition to social isolation during the current pandemic removes young children in the most vulnerable age group (2-5 years) from the most likely source of the common but unidentified infections that are believed to trigger ALL in susceptible individuals harboring covert preleukemic clones.2 A reduction in incidence of ALL would be expected to follow, as was observed during the 2003 SARS epidemic and year-long school closure in Hong Kong.5 It is possible to test and deconvolute these two scenarios. Cases of ALL diagnosed over 2020 and beyond could be screened for viral antibodies in blood plasma (as for AH1N14). Comparison of changes in incidence rates of ALL in regions and countries with widely differing SARS-coV-2 infection rates might be informative, as would comparisons with countries with no school-closure policy (Sweden). Finally, any such impacts on incidence of ALL, in either direction, are anticipated to be selective for the major B-cell precursor subtype.2 Children diagnosed with other leukemias or solid tumors over the same time period would provide a valuable control group and help accommodate some potential confounders such as diagnostic delays during the COVID-19 health crisis. Studies along these lines have been initiated in some European countries. Hopefully, these will be expanded and include international collaboration. The author declares that there is no conflict of interest.