Development and validation of a nomogram for predicting occurrence of severe case in children hospitalized with influenza A (H1N1) infection during the post-COVID-19 era.

Background: The significant rebound of influenza A (H1N1) virus activity, particularly among children, with rapidly growing number of hospitalized cases is of major concern in the post-COVID-19 era. The present study was performed to establish a prediction model of severe case in pediatric patients hospitalized with H1N1 infection during the post-COVID-19 era. Methods: This is a multicenter retrospective study across nine public tertiary hospitals in Yunnan, China, recruiting pediatric H1N1 inpatients hospitalized at five of these centers between February 1 and July 1, 2023, into the development dataset. Screening of 40 variables including demographic information, clinical features, and laboratory parameters were performed utilizing Least Absolute Shrinkage and Selection Operator (LASSO) regression and logistic regression to determine independent risk factors of severe H1N1 infection, thus constructing a prediction nomogram. Receiver operating characteristic (ROC) curve, calibration curve, as well as decision curve analysis (DCA) were employed to evaluate the model's performance. Data from four independent cohorts comprised of pediatric H1N1 inpatients from another four hospitals between July 25 and October 31, 2023, were utilized to externally validate this nomogram. Results: The development dataset included 527 subjects, 122 (23.1 %) of whom developed severe H1N1 infection. The external validation dataset included 352 subjects, 72 (20.5 %) of whom were eventually confirmed as severe H1N1 infection. The LASSO regression identified 19 candidate predictors, with logistic regression further narrowing down to 11 independent risk factors, including underlying conditions, prematurity, fever duration, wheezing, poor appetite, leukocyte count, neutrophil-lymphocyte ratio (NLR), erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α). By integrating these 11 factors, a predictive nomogram was established. In terms of prediction of severe H1N1 infection, excellent discriminative capacity, favorable accuracy, and satisfactory clinical usefulness of this model were internally and externally validated via ROC curve, calibration curve, and DCA, respectively. Conclusion: Our study successfully established and validated a novel nomogram model integrating underlying conditions, prematurity, fever duration, wheezing, poor appetite, leukocyte count, NLR, ESR, LDH, IL-10, and TNF-α. This nomogram can effectively predict the occurrence of serious case in pediatric H1N1 inpatients during the post-COVID-19 era, facilitating the early recognition and more efficient clinical management of such patients.

Evaluation of febrile seizures in children infected with SARS-CoV-2 Omicron variant in Yunnan, China: a multi-center, retrospective observational study.

Background: The SARS-CoV-2 Omicron variant was reported to be linked to febrile seizures (FSs), but studies on FSs in children with Omicron infection remain relatively scarce, especially in the Chinese population. This study aimed to investigate the characteristics of children diagnosed with Omicron infection with FSs in Yunnan, China, and evaluate the potential association between FSs and Omicron infection. Methods: This study was conducted at four hospitals in Yunnan from December 8, 2022, to January 8, 2023, and consisted of 590 pediatric subjects. According to clinical characteristics, 85, 129 and 376 subjects were divided into the FS-only, Omicron-FS, and Omicron-only groups, respectively. Demographic, clinical and laboratory data were retrospectively collected for analysis. Results: The incidence of FSs in children with Omicron infection was 25.5% (129/505). Older age, stronger male predominance, as well as lower proportions of prior history and family history of seizures were observed in Omicron-FS and Omicron-only groups than in FS-only group, but there were no differences in these four above-mentioned events between these two Omicron-related groups. Compared to FS-only group, Omicron-FS group also had a shorter fever-to-seizure onset duration and more frequent seizures during a single course of fever. Moreover, higher levels of IL-6, TNF-α and ferritin as well as decreased counts of leukocytes and lymphocytes were confirmed in Omicron-FS group than in FS-only and Omicron-only groups. Regarding COVID-19 vaccination status, Omicron-FS group revealed a higher proportion of unvaccinated children and a lower proportion of three-dose vaccination than Omicron-only group. As for clinical outcomes, proportions of mechanical ventilation and intensive care unit admission observed in the two Omicron-related groups were notably higher than those in FS-only group. Meanwhile, Omicron-FS group showed the longest length of hospital stay, followed by Omicron-only group and FS-only group, in order. Finally, all patients but one who died of fulminant myocarditis had been successfully discharged. Conclusions: The incidence of FSs in children with Omicron infection was 25.5% in Yunnan. FSs might be a clinical sign deserving more attention in children with Omicron infection. Furthermore, COVID-19 vaccination is likely to provide effective protection against Omicron-related FSs in children.

A novel de novo heterozygous variant of the KCNQ2 gene: Contribution to early­onset epileptic encephalopathy in a female infant.

Early­onset epileptic encephalopathy (EOEE) represents one of the most severe epilepsies, characterized by recurrent seizures during early infancy, electroencephalogram (EEG) abnormalities and varying degrees of neurodevelopmental delay. The KCNQ2 gene has been reported to have a major role in EOEE. In the present study, a 3­month­old female infant from the Chinese Lisu minority with EOEE was analyzed. Detailed clinical evaluations and next­generation sequencing were performed to investigate the clinical and genetic characteristics of this patient, respectively. Furthermore, the three­dimensional structure of the mutant protein was predicted by SWISS­Model and the expression of KCNQ2 protein in the patient was assessed by flow cytometry. It was observed that the patient presented with typical clinical features of EOEE, including repeated non­febrile seizures and significant EEG abnormalities. A novel heterozygous missense variant c.431G>C (p.R144P) in KCNQ2 was identified in the patient and the genotyping of KCNQ2 in the patient's parents suggested that this variant was de novo. Subsequently, the breakage of hydrogen bonds between certain amino acids was predicted by structural analysis of the mutant protein. Flow cytometric analysis detected a significant reduction buts not complete loss of native KCNQ2 protein expression in the patient (25.1%). In conclusion, a novel variant in KCNQ2 was confirmed as the genetic cause for EOEE in this patient. The present study expanded the pathogenic mutation spectrum of KCNQ2, enhanced the understanding of the molecular pathogenesis of EOEE and provided novel clues for research on the genotype­phenotype correlation in this disease.