Severe COVID-19 in children during the Omicron BA.5 and XBB waves: clinical characteristics and risk factors

<title>Abstract</title> <p> Background As the coronavirus disease 2019 (COVID-19) pandemic persists amid the ongoing evolution of its causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), updated clinical characterization of infected children is needed. This study analyzed the clinical characteristics of children infected with SARS-CoV-2 Omicron BA.5 and XBB variants and the risk factors for severe/critical disease. Methods We retrospectively reviewed the clinical data of pediatric COVID-19 inpatients admitted to the Fifth Hospital of Xiamen between December 2022 and December 2025. Clinical classification, underlying comorbidities, symptoms, laboratory test results, co-infection rate, and complications were compared between the Omicron BA.5 and XBB periods. Independent risk factors for severe/critical disease were identified using multivariable logistic regression analysis. Results Of the 519 hospitalized patients, 345 (66.4%) were infants or toddlers. Patients were categorized into mild (192 cases, 37.0%), moderate (227 cases, 43.7%), and severe/critical (100 cases, 19.3%) groups. All the patients improved or achieved clinical recovery. Compared with the Omicron BA.5 period, the XBB period showed lower incidence of severe/critical disease, lower oxygen requirement, shorter median hospital stay, and fewer complications (all <italic>P</italic>  &lt; 0.05). Neurological symptoms were more frequent during the Omicron BA.5 period ( <italic>P</italic>  &lt; 0.05), whereas co-infection rate did not significantly differ between the two periods. Multivariable logistic regression identified neurological symptoms as the strongest independent predictor of severe/critical disease, reflecting their near-exclusive occurrence in severe or critical cases. Other independent risk factors included Omicron BA.5 period, hyponatremia, infancy, toddlerhood, and elevated neutrophil count (all <italic>P</italic>  &lt; 0.05). Underlying disease and co-infection were not independently associated with severe/critical disease. Conclusions Clinical severity significantly declined from the Omicron BA.5 period to the XBB period. Infancy, toddlerhood, hyponatremia, and elevated neutrophil count are independent risk factors for severe/critical disease, whereas co-infection and underlying comorbidities are not. Neurological symptoms are the strongest independent predictor of severe/critical disease and thus should be prioritized during severity assessment, particularly in infants and toddlers. Routine monitoring of serum sodium level should also be considered. </p>