Unique Changes in the Incidence of Acute Chest Syndrome in Children With Sickle Cell Disease Unravel the Role of Respiratory Pathogens: A Time Series Analysis

Abstract

Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD). Although respiratory pathogens are frequently detected in children with ACS, their respective role in triggering the disease is still unclear. We hypothesized that the incidence of ACS followed the unprecedented population-level changes in respiratory pathogen dynamics after COVID-19-related nonpharmaceutical interventions (NPIs). What is the respective role of respiratory pathogens in ACS epidemiology? This study was an interrupted time series analysis of patient records from a national hospital-based surveillance system. All childrenaged < 18 years with SCD hospitalized for ACS in France between January 2015 and May 2022 were included. The monthly incidence of ACS per 1,000 children with SCD over time was analyzed by using a quasi-Poisson regression model. The circulation of 12 respiratory pathogens in the general pediatric population over the same period was included in the model to assess the fraction of ACS potentially attributable to each respiratory pathogen. Among the 55,941 hospitalizations of children with SCD, 2,306 episodes of ACS were included (median [interquartile range] age, 9 [5-13] years). A significant decrease was observed in ACS incidence after NPI implementation in March 2020 (-29.5%; 95%CI, -46.8 to -12.2; P= .001) and a significant increase after lifting of the NPIs in April 2021 (24.4%; 95%CI, 7.2 to 41.6; P= .007). Using population-level incidence of several respiratory pathogens, Streptococcus pneumoniae accounted for 30.9%(95%CI, 4.9 to 56.9; P= .02) of ACS incidence over the study period and influenza 6.8%(95%CI, 2.3 to 11.3; P= .004); other respiratory pathogens had only a minor role. NPIs were associated with significant changes in ACS incidence concomitantly with major changes in the circulation of several respiratory pathogens in the general population. This unique epidemiologic situation allowed determination of the contribution of these respiratory pathogens, in particular S pneumoniae and influenza, to the burden of childhood ACS, highlighting the potential benefit of vaccine prevention in this vulnerable population.