High incidence of cerebrovascular lesions on magnetic resonance imaging in pediatric COVID-19 during omicron outbreak - A retrospective case series.

BACKGROUND: The incidence of pediatric hospitalizations has significantly increased since the spread of the omicron variant of COVID-19. Changes of characteristics in respiratory and neurological symptoms have been reported. We performed a retrospective, cross-sectional study to characterize the MRI change in children with an emphasis on the change of cerebral vasculatures. METHODS: We retrospectively collected clinical and MRI data of 31 pediatric patients with neurological symptoms during the acute infection and abnormalities on MRI during the outbreak of omicron variant from April 2022 to June 2022 in Taiwan. The clinical manifestations and MRI abnormalities were collected and proportion of patients with vascular abnormalities was calculated. RESULTS: Among 31 pediatric patients with post-COVID-19 neurological symptoms, MRI abnormalities were observed in 15 (48.4%), predominantly encephalitis/encephalopathy (73.3%). Notable MRI findings included focal diffusion-weighted imaging (DWI) hyperintensity in cerebral cortex and thalamus, diffuse cortical T2/DWI hyperintensity, and lesions in the medulla, pons, cerebellum, and splenium of corpus callosum. Vascular abnormalities were seen in 12 (80%) patients with MRI abnormalities, mainly affecting the middle cerebral arteries. The spectrum of neurological manifestations ranged from seizures to Alice in Wonderland syndrome, underscoring the diverse impact of COVID-19 on pediatric patients. CONCLUSION: A high proportion of vascular abnormalities was observed in pediatric patients with neurological involvements, suggesting that vascular involvement is an important mechanism of neurological manifestations in omicron variant infection.

Machine learning models to evaluate mortality in pediatric patients with pneumonia in the intensive care unit.

OBJECTIVES: This study aimed to predict mortality in children with pneumonia who were admitted to the intensive care unit (ICU) to aid decision-making. STUDY DESIGN: Retrospective cohort study conducted at a single tertiary hospital. PATIENTS: This study included children who were admitted to the pediatric ICU at the National Taiwan University Hospital between 2010 and 2019 due to pneumonia. METHODOLOGY: Two prediction models were developed using tree-structured machine learning algorithms. The primary outcomes were ICU mortality and 24-h ICU mortality. A total of 33 features, including demographics, underlying diseases, vital signs, and laboratory data, were collected from the electronic health records. The machine learning models were constructed using the development data set, and performance matrices were computed using the holdout test data set. RESULTS: A total of 1231 ICU admissions of children with pneumonia were included in the final cohort. The area under the receiver operating characteristic curves (AUROCs) of the ICU mortality model and 24-h ICU mortality models was 0.80 (95% confidence interval [CI], 0.69-0.91) and 0.92 (95% CI, 0.86-0.92), respectively. Based on feature importance, the model developed in this study tended to predict increased mortality for the subsequent 24 h if a reduction in the blood pressure, peripheral capillary oxygen saturation (SpO2 ), or higher partial pressure of carbon dioxide (PCO2) were observed. CONCLUSIONS: This study demonstrated that the machine learning models for predicting ICU mortality and 24-h ICU mortality in children with pneumonia have the potential to support decision-making, especially in resource-limited settings.

Risk Factors for Severe Respiratory Syncytial Virus Infection in Hospitalized Children.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of bronchiolitis and pneumonia in infants and young children. Starting in December 2010, RSV monoclonal antibody (RSV mAb) was endorsed by Taiwan National Health Insurance and given to children with prematurity and/or congenital heart diseases, which are considered high-risk factors for severe RSV diseases. Investigating other important contributing risk factors is warranted. METHODS: We conducted a cohort study at National Taiwan University Hospital to determine the rate of severe outcomes among children hospitalized due to RSV infection from 2008 to 2018. Adjusted for age, sex and birth cohorts born before and after RSV mAb endorsement, we identified risk factors for severe RSV infection, defined as the requirement of invasive ventilator support. RESULTS: There were 1985 admissions due to RSV infections. Among them, 66 patients (3.3%) had severe RSV infection. The proportion of severe RSV infections decreased significantly after RSV mAb endorsement. Multivariable analysis revealed that age <1.5 months and cardiovascular and congenital/genetic diseases were high-risk underlying conditions. In addition, bacterial coinfections, elevated creatinine levels and initial abnormal chest radiograph findings posed warning signs for severe RSV infection. CONCLUSIONS: Children younger than 1.5 months of age with cardiovascular or congenital/genetic diseases were predisposed to severe RSV infection and might benefit from RSV mAb prophylaxis.

Clinical manifestations and risk factors of shock in children with multisystem inflammatory syndrome.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a novel disease associated with COVID-19. The COVID-19 epidemic peaked in May 2022 in Taiwan, and we encountered our first case of MIS-C in late May 2022. We aimed to present patients' clinical manifestations and identify risk factors for shock. METHODS: We included patients diagnosed with MIS-C at two medical centers from May 2022 to August 2022. We separated those patients into two groups according to whether they experienced shock. We collected demographic, clinical manifestation, and laboratory data of the patients and performed statistical analysis between the two groups. RESULTS: We enrolled 28 patients, including 13 (46 %) with shock and 15 (54 %) without shock. The median age was 6.4 years (IQR: 1.9-7.5). In single variable analysis, patients with shock tended to be older, had more neurological symptoms, more conjunctivitis and strawberry tongue, lower lymphocyte count, lower platelet counts, and higher C-reactive protein, higher procalcitonin, higher ferritin, and higher D-dimer levels than those without shock. The area under the ROC curve that used procalcitonin to be the risk factor of shock with MIS-C was 0.815 (95 % CI 0.644 to 0.987). The cutoff value obtained by ROC analysis of procalcitonin was 1.68 ng/mL. With this cutoff, the test characteristics of procalcitonin were as follows: sensitivity 77 %, specificity 93 %, positive predictive value 91 %, negative predictive value 82 %. Multivariable analysis revealed that procalcitonin was the only independent risk factor of shock with MIS-C on admission (OR, 26.00, 95 % CI, 1.01-668.89). CONCLUSIONS: MIS-C patients with high initial procalcitonin levels have higher risks of experiencing shock and may need ICU admission.

Outcomes of pediatric community-acquired pneumonia before and after national pneumococcal immunization in Taiwan.

OBJECTIVE: In Taiwan, the incidence of invasive pneumococcal disease (IPD) in children declined after the catch-up primary vaccination programs and the full national immunization program (NIP) with PCV13. The objective of the study was to investigate the clinical outcomes of pediatric community-acquired pneumonia (CAP) before and after the NIP. METHODS: The study included patients aged 3 months to 17 years who were diagnosed with CAP and treated at the National Taiwan University Hospital between 2007 and 2019. Patients were assigned to three birth cohorts according to their birth years and vaccination eligibility: non-NIP, catch-up, and full NIP. We compared the rates of severe outcomes, including case fatality and pathogens. RESULTS: A total of 6557 patients who met the CAP criteria were enrolled during the study period. The case-fatality rate decreased from 3.2% (94/2984) in the non-NIP cohort to 0.3% (7/2176) in the catch-up cohort and 0.8% (11/1397) in the full NIP cohort (p < 0.001). Furthermore, there was a significant decrease in invasive ventilation from the non-NIP (17.9%) to both catch-up (6.8%) and full NIP cohorts (9.1%). The rate of IPD declined from the non-NIP cohort to the catch-up cohort (1.8% vs. 0.6%, p < 0.001) and from the catch-up to the full NIP cohort (0.6% vs. 0.07%, p = 0.014). In contrast, the rates of infections with other pathogens increased after NIP. CONCLUSION: The introduction of PCV13 showed significant reduction in case-fatality and IPD rates. The increasing rates of other pathogens warrant further surveillance for their clinical significance.

Clinical characteristics and factors associated with severe COVID-19 in hospitalized children during the SARS-CoV-2 Omicron pandemic in Taiwan.

BACKGROUND: Since April 2022, a notable increase in COVID-19 cases with the rapid spread of the SARS-CoV-2 Omicron variant has been reported in Taiwan. In the epidemic, children were one of the most vulnerable groups, so we analyzed their clinical presentations and factors associated with severe complications of COVID-19 in children. METHODS: We included hospitalized patients under 18 years old with lab-confirmed SARS-CoV-2 infection from March 1, 2022, to July 31, 2022. We collected the demographic and clinical characteristics of the patients. Patients requiring intensive care were defined as severe cases. RESULTS: Among the 339 enrolled patients, the median age was 31 months (interquartile range (IQR), 8-79.0 months); and 96 patients (28.3%) had underlying diseases. Fever was noted in 319 patients (94.1%) with a median duration of two days (IQR 2-3 days). Twenty-two patients (6.5%) were severe cases, including 10 patients (2.9%) with encephalopathy with abnormal neuroimaging and ten patients (2.9%) with shock. Two patients (0.6%) died. Patients with congenital cardiovascular disease (aOR: 21.689), duration of fever up to four days or more (aOR: 6.466), desaturation (aOR: 16.081), seizure (aOR: 20.92), and procalcitonin >0.5 ng/mL (aOR: 7.886) had a higher risk of severe COVID-19. CONCLUSIONS: Vital signs need close monitoring, early management and/or intensive care may be applied in COVID-19 patients with congenital cardiovascular diseases, fever lasting ≥4 days, seizures, desaturation and/or elevated procalcition since they are at higher risks of severe diseases.

Serostatus of echovirus 11, coxsackievirus B3 and enterovirus D68 in cord blood: The implication of severe newborn enterovirus infection.

BACKGROUND: Maternal transplacental antibody is an important origins of passive immunity against neonatal enterovirus infection. Echovirus 11 (E11) and coxsackievirus B3 (CVB3) are important types causing neonatal infections. There were few investigations of enterovirus D68 (EVD68) infection in neonates. We aimed to investigate the serostatus of cord blood for these three enteroviruses and evaluate the factors associated with seropositivity. METHODS: We enrolled 222 parturient (gestational age 34-42 weeks) women aged 20-46 years old between January and October 2021. All participants underwent questionnaire investigation and we collected the cord blood to measure the neutralization antibodies against E11, CVB3 and EVD68. RESULTS: The cord blood seropositive rates were 18% (41/222), 60% (134/232) and 95% (211/222) for E11, CVB3 and EVD68, respectively (p < 0.001). Geometric mean titers were 3.3 (95% CI 2.9-3.8) for E11, 15.9 (95% CI 12.5-20.3) for CVB3 and 109.9 (95% CI 92.4-131.6) for EVD68. Younger parturient age (33.8 ± 3.6 versus 35.2 ± 4.4, p = 0.04) was related to E11 seropositivity. Neonatal sex, gestational age and birth body weight were not significantly different between the seropositive group and the seronegative group. CONCLUSION: Cord blood seropositive rate and geometric mean titer of E11 were very low, so a large proportion of newborns are susceptible to E11. The circulation of E11 was low after 2019 in Taiwan. A large cohort of immune naïve newborns existed currently due to lack of protective maternal antibodies. It is imminent to monitor the epidemiology of neonates with enterovirus infections and strengthen the relevant preventive policies.

Pediatric glomerulopathy after COVID-19 vaccination: A case series and review of the literature.

BACKGROUND: Cases of glomerulopathy after COVID-19 vaccination have been reported in the adult population, while only a few cases have been reported in children and adolescents. For better understanding of this association in pediatric population, we aimed to describe clinical course of patients with glomerulopathy within 60 days of COVID-19 vaccination who were under followed up in the pediatric nephrology department of National Taiwan University Children's Hospital. METHODS: We reviewed the clinical characteristics, vaccine types, and outcomes of patients with newly diagnosed glomerular diseases or relapse of underlying glomerulopathy within 60 days after COVID-19 vaccination at our facility between January 2021 and July 2022. RESULTS: Thirteen pediatric patients were found to have newly diagnosed glomerular diseases or relapse from their underlying glomerulopathy after receiving their first, second, or third COVID-19 vaccines in our facility. Of the five pediatric patients with newly diagnosed glomerulopathy after vaccination, thin basement membrane nephropathy, idiopathic nephrotic syndrome, and hematuria have been identified. Seven patients had relapse episodes of underlying nephrotic syndrome and one patient with underlying isolated microscopic hematuria developed subnephrotic proteinuria after COVID-19 vaccination. All patients experienced remission or improvement with either immunosuppressive or conservative treatment during the follow-up period. CONCLUSIONS: This is the largest case series to date of pediatric glomerulopathy after COVID-19 vaccination. From our report, patients with either newly diagnosed or relapse of glomerulopathy after vaccination had good outcomes, and receiving vaccination to prevent COVID-19 infection or complications should be encouraged in pandemic era under close monitoring kidney manifestations.

Viral dynamics of SARS-CoV-2 Omicron infections in a previously low COVID-19 prevalence region: Effects of vaccination status, antiviral agents, and age.

BACKGROUND: In Taiwan, the prevalence of COVID-19 was low before April 2022. The low SARS-CoV-2 seroprevalence in the population of Taiwan provides an opportunity for comparison with fewer confounding factors than other populations globally. Cycle threshold (Ct) value is an easily accessible method for modeling SARS-CoV-2 dynamics. In this study, we used clinical samples collected from hospitalized patients to explore the Ct value dynamics of the Omicron variant infection. METHODS: From Jan 2022 to May 2022, we retrospectively included hospitalized patients tested positive by nasopharyngeal SARS-CoV-2 PCR. We categorized the test-positive subjects into different groups according to age, vaccination status, and use of antiviral agents. To investigate the nonlinear relationship between symptom onset days and Ct value, a fractional polynomial model was applied to draw a regression line. RESULTS: We collected 1718 SARS-CoV-2 viral samples from 812 individuals. The Ct values of unvaccinated individuals were lower than those of vaccinated persons from Day 4 to Day 10 after symptom onset. The Ct value increased more rapidly in those individuals with antiviral drug treatment from Day 2 to Day 7. In elderly individuals, the Ct values increased slowly from Day 5 to Day 10, and the increasing trend was unique compared with that in children and adults. CONCLUSION: Our study demonstrated the primary viral infection dynamics of the Omicron variant in hospitalized patients. Vaccination significantly affected viral dynamics, and antiviral agents modified viral dynamics irrespective of vaccination status. In elderly individuals, viral clearance is slower than that in adults and children.

Clinical characteristics of hospitalized children with community-acquired pneumonia and respiratory infections: Using machine learning approaches to support pathogen prediction at admission.

BACKGROUND: Acute respiratory infections (ARIs) are common in children. We developed machine learning models to predict pediatric ARI pathogens at admission. METHODS: We included hospitalized children with respiratory infections between 2010 and 2018. Clinical features were collected within 24 h of admission to construct models. The outcome of interest was the prediction of 6 common respiratory pathogens, including adenovirus, influenza virus types A and B, parainfluenza virus (PIV), respiratory syncytial virus (RSV), and Mycoplasma pneumoniae (MP). Model performance was estimated using area under the receiver operating characteristic curve (AUROC). Feature importance was measured using Shapley Additive exPlanation (SHAP) values. RESULTS: A total of 12,694 admissions were included. Models trained with 9 features (age, event pattern, fever, C-reactive protein, white blood cell count, platelet count, lymphocyte ratio, peak temperature, peak heart rate) achieved the best performance (AUROC: MP 0.87, 95% CI 0.83-0.90; RSV 0.84, 95% CI 0.82-0.86; adenovirus 0.81, 95% CI 0.77-0.84; influenza A 0.77, 95% CI 0.73-0.80; influenza B 0.70, 95% CI 0.65-0.75; PIV 0.73, 95% CI 0.69-0.77). Age was the most important feature to predict MP, RSV and PIV infections. Event patterns were useful for influenza virus prediction, and C-reactive protein had the highest SHAP value for adenovirus infections. CONCLUSION: We demonstrate how artificial intelligence can assist clinicians identify potential pathogens associated with pediatric ARIs upon admission. Our models provide explainable results that could help optimize the use of diagnostic testing. Integrating our models into clinical workflows may lead to improved patient outcomes and reduce unnecessary medical costs.

Clinical manifestations and risk factors of campylobacter gastroenteritis in children in Taiwan.

BACKGROUND: Campylobacteriosis is a common cause of bacterial gastroenteritis worldwide. This study aimed to investigate the potential risk factors, clinical and laboratory manifestations of children with campylobacteriosis under five years old in Taiwan. METHODS: This retrospective case-control study was conducted in ten major hospitals in Taiwan from 2014 to 2017. Laboratory tests and stool specimen were collected and analyzed together with questionnaire survey. Multivariate stepwise logistic regression model was used for identification of risk factors. RESULTS: A total of 64 campylobacteriosis cases were included with a median age of 25 months. We observed a less prolonged vomiting (p = 0.047), more bloody (p < 0.001) and mucoid (p = 0.005) stools, and lower AST levels (p = 0.020) in patients with campylobacteriosis. Lower parental educational attainment (p < 0.001), direct contact with acute gastroenteritis patients (p < 0.001), as well as diarrhea in the mutually cared children (p = 0.007) were linked to campylobacteriosis. Consumption of municipal water (p < 0.001), milk (OR 0.34, 95% CI 0.118-0.979), and soft beverages (OR 0.41, 95% CI 0.192-0.888) were identified as protective factors, while consuming takeout food (p = 0.032) and seafood (p = 0.019) increased risk of campylobacteriosis. CONCLUSIONS: Shorter vomiting duration, bloody and mucoid stool, and less elevated AST levels are manifestations suggestive of campylobacteriosis. Risk factors of campylobacteriosis were low parental educational attainment, direct contact with acute gastroenteritis patients, diarrhea in mutually cared children, takeout food and seafood intake. Potential protective factors include municipal water, milk, and soft beverage intake.

The clinical predictors of and vaccine protection against severe influenza infection in children.

Influenza infection in children causes a tremendous global burden. In this study, we aimed to investigate the clinical predictors of severe influenza among children. We retrospectively included hospitalized children who had laboratory-confirmed influenza infection and were admitted to a medical center in Taiwan between 2010 and 2018. Severe influenza infection was defined as needing intensive care. We compared demographics, comorbidities, vaccine status and outcomes between patients with severe and nonsevere infection. There were 1030 children hospitalized for influenza infection: 162 patients needed intensive care and 868 patients did not. Multivariable analysis revealed that an age below 2 years (adjusted odds ratio [aOR] 3.31, 95% confidence interval [CI] 2.22-4.95), underlying cardiovascular disease (aOR 1.84, 95% CI 1.04-3.25), neuropsychological (aOR 4.09, 95% CI 2.59-6.45) or respiratory disease (aOR 3.87, 95% CI 1.42-10.60), patchy infiltrates (aOR 2.52, 95% CI 1.29-4.93), pleural effusion (aOR 6.56, 95% CI 1.66-25.91), and invasive bacterial coinfection (aOR 21.89, 95% CI 2.19-218.77) were significant clinical predictors of severe disease, whereas severe infection was less likely in individuals who had received influenza and pneumococcal conjugate vaccines (PCVs) (aOR 0.51, 95% CI 0.28-0.91; aOR 0.35, 95% CI 0.23-0.51, respectively). The most significant risk factors associated with severe influenza infection were an age under 2 years, comorbidities (cardiovascular, neuropsychological, and respiratory diseases), patchy infiltrates or effusion shown on chest X-rays, and bacterial coinfections. The incidence rate of severe disease was significantly lower in those who had received influenza vaccines and PCVs.

Differential clinical characteristics and performance of home antigen tests between parents and children after household transmission of SARS-CoV-2 during the Omicron variant pandemic.

OBJECTIVES: The SARS-CoV-2 Omicron variant pandemic struck Taiwan in April 2022. Rapid antigen tests (RATs) play an important role in providing rapid results during a pandemic. However, self-collected samples by the children's caregivers without the supervision of medical personnel raise some concerns. METHODS: This study was performed to investigate household transmission, clinical characteristics, and antigen performance in a special COVID-19 family clinic in a children's hospital. The performance of at-home RATs was evaluated based on reverse transcription-polymerase chain reaction. RESULTS: We included 627 patients in our study between May 11 and June 10, 2022. The COVID-19 full vaccination rate was significantly higher in adults (98.5%) than in children (5.9%, P <0.001). The transmission rate was significantly higher in children (91.3%) than in adults (76.6%, P <0.001). Infected children had more incidents of fever (82.4% vs 22.4%, P <0.001) and a higher peak fever than adults. Based on the reverse transcription-polymerase chain reaction, the negative predictive rate of the home RAT was only 38.7% (95% confidence interval: 31.9-46.0%) in children. The cycle threshold value of those with false-negative antigen tests was significantly lower in children. CONCLUSION: Children had a higher transmission rate, more fever, and higher peak fever than adults. Home RAT has a suboptimal negative predictive rate in children.

The impact of the coronavirus disease 2019 epidemic and national public restrictions on Pediatric Intensive Care Units in Taiwan.

BACKGROUND/PURPOSE: Coronavirus disease 2019 (COVID-19) pandemic challenges pediatric health globally by limited medical accessibility. In response to COVID-19 epidemic in Taiwan, public restrictions were applied and the Level 3 alert was announced from May to July in 2021 for local outbreak. This study aims to analyze patients' clinical features and outcomes in the pediatric intensive care unit (PICU) during the COVID-19 epidemic with the Level 3 alert in Taiwan. METHODS: Medical records were retrospectively collected in patients admitted to the PICU of National Taiwan University Children's Hospital from May to July 2021 (Level 3 alert) and May to July 2019 and 2020 (control periods). Clinical characteristics and outcomes were compared between patients in the period with the Level 3 alert and control periods. RESULTS: During the study period, PICU monthly admissions significantly decreased in the Level 3 alert period and were negatively correlated with monthly newly confirmed COVID-19 cases. Patients admitted during the Level 3 alert were older, had higher disease severity, lower proportion of cardiovascular disease, and higher proportion of hematology-oncology diseases than those in the control group. After adjusting for the above factors, admission during Level 3 alert was an independent factor for higher mortality rate and prolonged length of stay (>14 days) in the PICU. CONCLUSION: During the COVID-19 epidemic with strict public restrictions, critically ill patients admitted to the PICU decreased but had increased disease severity, prolonged length of stay in the PICU, and higher mortality, reflecting the impact of quarantine and limited medical access.

Application of nested multiplex polymerase chain reaction respiratory and pneumonia panels in children with severe community-acquired pneumonia.

Community-acquired pneumonia (CAP) is a serious clinical concern. A lack of accurate diagnosis could hinder pathogen-directed therapeutic strategies. To solve this problem, we evaluated clinical application of nested multiplex polymerase chain reaction (PCR) in children with severe CAP. We prospectively enrolled 60 children with severe CAP requiring intensive care between December 2019 and November 2021 at a tertiary medical center. Nested multiplex PCR respiratory panel (RP) and pneumonia panel (PP) were performed on upper and lower respiratory tract specimens. We integrated standard-of-care tests and quantitative PCR for validation. The combination of RP, PP, and standard-of-care tests could detect at least one pathogen in 98% of cases and the mixed viral-bacterial detection rate was 65%. The positive percent agreement (PPA), and negative percent agreement (NPA) for RP were 94% and 99%; the PPA and NPA for PP were 89% and 98%. The distribution of pathogens was similar in the upper and lower respiratory tracts, and the DNA or RNA copies of pathogens in the lower respiratory tract were equal to or higher than those in the upper respiratory tract. PP detected bacterial pathogens in 40 (67%) cases, and clinicians tended to increase bacterial diagnosis and escalate antimicrobial therapy for them. RP and PP had satisfactory performance to help pediatricians make pathogenic diagnoses and establish therapy earlier. The pathogens in the upper respiratory tract had predictive diagnostic values for lower respiratory tract infections in children with severe CAP.

Clinical characteristics and outcomes of carbapenem-resistant Enterobacterales bacteremia in pediatric patients.

BACKGROUND/PURPOSE: Clinical data on carbapenem-resistant Enterobacterales (CRE) bacteremia in the pediatric population are limited. This study investigated the clinical characteristics and outcomes of pediatric CRE bacteremia. METHODS: Clinical data on bacteremia caused by carbapenem-susceptible and carbapenem-resistant Enterobacterales, including Escherichia coli, Klebsiella spp., Enterobacter spp., Serratia marcescens, Proteus mirabilis, Citrobacter spp., and Morganella spp., in pediatric patients from a children's hospital in Taiwan were retrospectively retrieved and analyzed. RESULTS: From January 2013 to December 2021, 471 clinical isolates of Enterobacterales bacteremia were identified in 451 episodes from 379 pediatric patients. Among all the isolates, the predominant species were E. coli (199/471, 42.2%), Klebsiella spp. (168/471, 35.6%), and Enterobacter spp. (59/471, 12.5%), with carbapenem-resistance rates of 1.5%, 11.9%, and 25.0%, respectively. Overall, 40 (8.4%) showed a carbapenem resistance phenotype. Patients' all-cause mortality rate at 14 days was significantly higher in CRE bacteremia episodes than non-CRE ones (12.5% vs. 3.6%, p < 0.05). The predicting factor of a CRE bacteremia episode was the causative agent of Enterobacter spp. (adjusted OR of 2.551, CI 1.073-6.066, p < 0.05) and ESBL-producing phenotype (adjusted OR 14.268, CI 5.120-39.762, p < 0.001). CONCLUSION: Bloodstream infections caused by CRE are associated with a higher mortality rate in the pediatric population. Attention must be paid to preventing and managing pediatric patients with CRE infections.

Cross-protective humoral immunity to coronaviruses from SARS coronavirus 2-naïve sera of children with Kawasaki disease.

OBJECTIVES: SARS coronavirus 2 (SARS-CoV-2)-associated multi-system inflammatory syndrome in children indicates that viruses can trigger a Kawasaki disease (KD)-like hyperinflammation. A plausible hypothesis was that coronavirus-specific 'holes' in humoral immunity could cause both diseases. METHODS: To determine whether SARS-CoV-2-naïve patients with KD have inferior humoral immunity for the novel coronavirus, sera of children with KD and control children from year 2015 to 2021 were subjected to ELISA, microwestern, and neutralization assays to evaluate the capabilities in recognizing the receptor-binding domain of SARS-CoV-2, spotting spike proteins of three respiratory syndromic coronaviruses, and blocking SARS-CoV-2 from binding to angiotensin-converting enzyme 2 receptors in vitro, respectively. RESULTS: 29 patients with KD before 2019, 74 patients with KD in 2019 or 2020, 54 non-febrile controls, and 24 febrile controls were included in the study. SARS-CoV-2 was recognized on ELISA for both patients with KD in 2016 and those with KD in 2020. Microwestern demonstrated cross-reactive IgG in an all-or-none manner towards three spike proteins of syndromic coronaviruses regardless of sample year or KD status. The ratio between the sera that recognized all spike proteins and those that recognized none (51 vs. 47) was significantly higher from patients with KD than from non-febrile controls (17 vs. 32; p 0.047) but not from febrile controls (13 vs. 11; p 0.85). Most positive sera (12 of 17 controls, 5 of 8 patients with KD before 2019, and 28 of 33 patients with KD in 2019 or 2020) offered protection comparable to low-titre sera from the WHO reference panel. DISCUSSION: Humoral immunity of SARS-CoV-2-naïve children with KD was not inferior to that of controls in offering cross-protection against the novel coronavirus.

The secular trend of enterovirus A71 after the implementation of preventive measures in Taiwan.

BACKGROUND: Enterovirus A71 (EV A71) is one of the most important enteroviruses related to morbidity and mortality in children worldwide. This study aimed to analyse the secular trend of EV A71 in Taiwan from 1998 to 2020 and to evaluate the effectiveness of infection control measures. METHODS: We collected the epidemiological data of EV A71 from disease surveillance systems in Taiwan. We analysed the association between the secular trend of EV A71 and preventive measures such as hand washing, case isolation, and suspension of classes. RESULTS: The incidence of enterovirus infections with severe complications (EVSC) decreased from 16.25 per 100,000 children under six in 1998 to less than 9.73 per 100,000 children under six after 2012 (P = 0.0022). The mortality rate also decreased significantly, from 3.52 per 100,000 children under six in 1998 to 0 per 100,000 children under six in 2020 (P < 0.0001). The numbers of EVSC and fatalities were significantly higher in the years when EV A71 accounted for more than 10% of the annual predominant serotypes (p < 0.05). After the implementation of many non-pharmaceutical interventions in 2012, the incidence of EVSC and mortality rate decreased significantly (p < 0.001). CONCLUSIONS: After implementing active enterovirus surveillance and preventive measures, we found that the incidence of EVSC and fatalities due to EV A71 in Taiwan decreased significantly from 1998 to 2020. Continuous surveillance and strengthened infection control policies are still needed in the future.

Long-term psychiatric outcomes in youth with enterovirus A71 central nervous system involvement.

Long-term neurological and neurodevelopmental sequelae are a concerning issue for people with Enterovirus A71 (EV-A71) central nervous system (CNS) infection. Unfortunately, no longitudinal prospective clinical study has systematically investigated the consequences of EV-A71 CNS infection during early life on the later development of other psychiatric disorders. In this naturalistic longitudinal follow-up design, we followed forty-three youth, who got EV-A71 CNS involvement 6-18 years ago and were enrolled in other EV-A71 clinical studies then. Their psychiatric presentation, emotional/behavioral problems, and cognitive issues were examined using a psychiatrist-conducted diagnostic interview, parent- and self-rated questionnaires, and neuropsychological tests, respectively. We compared the prevalence of psychiatric disorders in youth with EV-A71 CNS involvement to a nationally representative cohort. Emotion/behavior and cognition in EV-A71-CNS-infected youth were compared to those in a matched community-based sample of healthy controls and youth with attention-deficit/hyperactivity disorder (ADHD). Compared to a national sample (absolute ADHD prevalence 10.1%), youth with EV-A71 CNS involvement had three times the odds of receiving an ADHD diagnosis (standardized prevalence ratio, 95% CI = 1.8, 4.2; absolute ADHD prevalence 34.9%). No other psychiatric diagnoses were more common in EV-A71-CNS-infected youth. Compared to community-based ADHD youth, EV-A71-CNS-infected youth with psychiatric disorders showed comparable core ADHD symptoms, opposition/defiance, autistic features, and suboptimal sustained attention performance (based on the Conners' Continuous Performance Test), all of which were more severe than healthy controls. EV-A71-CNS-infected youth without psychiatric disorders showed comparable autistic features to EV-A71-CNS-infected youth with psychiatric disorders and ADHD youth. EV-A71 CNS involvement may cause long-term, adverse psychiatric outcomes that develop into an ADHD diagnosis alongside social/communication/emotion problems and autistic features. We recommend earlier identification and intervention of these problems among these children.

Children with Mycoplasma pneumoniae infection in Taiwan: Changes in molecular characteristics and clinical outcomes.

BACKGROUND: Mycoplasma pneumoniae is a pathogen that causes respiratory diseases in children. Infections caused by M. pneumoniae are usually self-limited but occasionally can be severe. We observed emerging cases of severe mycoplasma infection requiring extracorporeal membrane oxygenation (ECMO). Thus, we investigated chronological changes in the molecular features of the M. pneumoniae and its clinical impacts among the pediatric population. METHODS: From 2011 to 2019, respiratory samples were collected from patients younger than 18 years old with pneumonia in a tertiary children's hospital. Focused multiple-locus variable number of tandem repeats analysis (MLVA) typing was performed on samples positive for M. pneumoniae in 2016 and 2019. Clinical data from the patients' electronic medical records were collected. We described the annual trend of macrolide resistance and MLVA type and analyzed the associations between clinical manifestations and MLVA types. RESULTS: The percentage of macrolide-resistant (MLR) M. pneumoniae gradually increased from 22% (27/122) in 2015 to 70% (82/117) in 2019. Among the MLRM. pneumoniae, the predominant strain shifted from type P (31% [13/42]) to type A (40% [19/46]). The demographics, initial presentations, and clinical courses of the subjects with MLRM. pneumoniae did not differ significantly between 2011 and 2019. However, in 2019, two fulminant cases requiring venovenous ECMO were observed, which indicates that more attention to the clinical severity of MLRM. pneumoniae infections is warranted. CONCLUSION: Obtaining accurate information on macrolide susceptibility is crucial for physicians to initiate appropriate antibiotic treatment in a timely fashion. Although we could not identify significant differences among mycoplasma pneumonias caused by different MLVAs over a span of 9 years, the emergence of severe mycoplasma infections requiring ECMO was clinically significant, and further monitoring was required.