Clinical Effectiveness of Biological Immunomodulators in SARS-CoV-2-Associated Multisystem Inflammatory Syndrome in Children: A Systematic Review.

BACKGROUND: Although there is consensus to use immunoglobulins and corticosteroids as first-line treatments for multisystem inflammatory syndrome in children (MIS-C), the effectiveness of biological immunomodulators in patients refractory to standard therapy remains unclear. We aimed to outline real-world data on biological immunomodulators. METHOD: A literature search using Ovid-Medline, EMBASE, Cochrane CDSR, and KMBASE was conducted from September 2021 to August 2022; certainty of evidence was assessed via GRADE. RESULTS: Among 258 studies, 10 were selected for analysis, of which 2 were observational studies (with control groups receiving standard therapy of either intravenous immunoglobulins and/or glucocorticoids) and 8 were single-arm studies. In all, 145 patients were treated with biological immunomodulators (anakinra (72; 49%) or infliximab (65; 44%)). In the first observational study, patients in the anakinra group initially exhibited a lower left ventricular ejection fraction than those in the control group. In the second study, patients in the infliximab group required less additional therapy and showed lower newly developed left ventricular dysfunction rate and reduced C-reactive protein levels. The clinical outcomes associated with each biological agent in single-arm studies were not reported individually. CONCLUSIONS: Biological immunomodulators are feasible therapeutic options for refractory MIS-C. Nevertheless, further research is warranted to demonstrate clinical efficacy.

Clinical Manifestations, Macrolide Resistance, and Treatment Utilization Trends of Mycoplasma pneumoniae Pneumonia in Children and Adolescents in South Korea.

A resurgence of Mycoplasma pneumoniae (MP)-the leading cause of community-acquired bacterial pneumonia, particularly in children-occurred following the COVID-19 pandemic. We aimed to investigate the clinical manifestations, macrolide resistance patterns, and therapeutic approaches related to the MP pneumonia epidemic. Children and adolescents diagnosed with MP pneumonia in September-December 2023 were screened. Clinical data were retrospectively collected from 13 major hospitals using concordant microbiological criteria, including either a positive PCR result or four-fold increase in serological markers. Demographic characteristics, treatment modalities, and clinical outcomes were analyzed. Of the 474 screened patients, 374 (median age: 7.7 [IQR, 5.4-9.6] years; hospitalization rate: 88.6%) met the microbiological confirmation criteria. Most patients experienced fever (98.9%), and lobular/lobar consolidation (59.1%) was the dominant radiological finding. The macrolide resistance rate remained high at 87.0%; corticosteroids were widely used (55.6%) alongside macrolides, despite resistance. Patients with consolidation had prolonged fever (median 8 vs. 7 days, p = 0.020) and higher hospitalization rates (92.3% vs. 83.0%, p = 0.008). Macrolide resistance did not significantly influence radiological outcomes. This study highlights the ongoing challenge of macrolide resistance in MP pneumonia and need for tailored therapeutic approaches. Despite high resistance, macrolides remain commonly prescribed, often concurrently with corticosteroids.

Antimicrobial resistance genes harbored in invasive Acinetobacter calcoaceticus-baumannii complex isolated from Korean children during the pre-COVID-19 pandemic periods, 2015-2020.

Background: Acinetobacter baumannii (AB) has emerged as one of the most challenging pathogens worldwide, causing invasive infections in the critically ill patients due to their ability to rapidly acquire resistance to antibiotics. This study aimed to analyze antibiotic resistance genes harbored in AB and non-baumannii Acinetobacter calcoaceticus-baumannii (NB-ACB) complex causing invasive diseases in Korean children. Methods: ACB complexes isolated from sterile body fluid of children in three referral hospitals were prospectively collected. Colistin susceptibility was additionally tested via broth microdilution. Whole genome sequencing was performed and antibiotic resistance genes were analyzed. Results: During January 2015 to December 2020, a total of 67 ACB complexes were isolated from sterile body fluid of children in three referral hospitals. The median age of the patients was 0.6 (interquartile range, 0.1-7.2) years old. Among all the isolates, 73.1% (n=49) were confirmed as AB and others as NB-ACB complex by whole genome sequencing. Among the AB isolates, only 22.4% susceptible to carbapenem. In particular, all clonal complex (CC) 92 AB (n=33) showed multi-drug resistance, whereas 31.3% in non-CC92 AB (n=16) (P<0.001). NB-ACB showed 100% susceptibility to all classes of antibiotics except 3rd generation cephalosporin (72.2%). The main mechanism of carbapenem resistance in AB was the bla oxa23 gene with ISAba1 insertion sequence upstream. Presence of pmr gene and/or mutation of lpxA/C gene were not correlated with the phenotype of colistin resistance of ACB. All AB and NB-ACB isolates carried the abe and ade multidrug efflux pumps. Conclusions: In conclusion, monitoring and research for resistome in ACB complex is needed to identify and manage drug-resistant AB, particularly CC92 AB carrying the bla oxa23 gene.

The Impact of an Antimicrobial Stewardship Program on Days of Therapy in the Pediatric Center: An Interrupted Time-Series Analysis of a 19-Year Study.

BACKGROUND: We aimed to analyze the effects of an antimicrobial stewardship program (ASP) on the proportion of antimicrobial-resistant pathogens in bacteremia, antimicrobial use, and mortality in pediatric patients. METHODS: A retrospective single-center study was performed on pediatric inpatients under 19 years old who received systemic antimicrobial treatment from 2001 to 2019. A pediatric infectious disease attending physician started ASP in January 2008. The study period was divided into the pre-intervention (2001-2008) and the post-intervention (2009-2019) periods. The amount of antimicrobial use was defined as days of therapy per 1,000 patient-days, and the differences were compared using delta slope (= changes in slopes) between the two study periods by an interrupted time-series analysis. The proportion of resistant pathogens and the 30-day overall mortality rate were analyzed by the χ². RESULTS: The proportion of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bacteremia increased from 17% (39 of 235) in the pre-intervention period to 35% (189 of 533) in the post-intervention period (P < 0.001). The total amount of antimicrobial use significantly decreased after the introduction of ASP (delta slope value = -16.5; 95% confidence interval [CI], -30.6 to -2.3; P = 0.049). The 30-day overall mortality rate in patients with bacteremia did not increase, being 10% (55 of 564) in the pre-intervention and 10% (94 of 941) in the post-intervention period (P = 0.881). CONCLUSION: The introduction of ASP for pediatric patients reduced the delta slope of the total antimicrobial use without increasing the mortality rate despite an increased incidence of ESBL-producing gram-negative bacteremia.

Cartilage-hair hypoplasia-anauxetic dysplasia spectrum disorders harboring RMRP mutations in two Korean children: A case report.

RATIONALE: Cartilage-hair hypoplasia (CHH, OMIM # 250250) is a rare autosomal recessive disorder, which includes cartilage-hair hypoplasia-anauxetic dysplasia (CHH-AD) spectrum disorders. CHH-AD is caused by homozygous or compound heterozygous mutations in the RNA component of the mitochondrial RNA-processing Endoribonuclease (RMRP) gene. PATIENT CONCERNS: Here, we report 2 cases of Korean children with CHH-AD. DIAGNOSES: In the first case, the patient had metaphyseal dysplasia without hypotrichosis, diagnosed by whole exome sequencing (WES), and exhibited only skeletal dysplasia and lacked extraskeletal manifestations, such as hair hypoplasia and immunodeficiency. In the second case, the patient had skeletal dysplasia, hair hypoplasia, and immunodeficiency, which were identified by WES. INTERVENTIONS: The second case is the first CHH reported in Korea. The patients in both cases received regular immune and lung function checkups. OUTCOMES: Our cases suggest that children with extremely short stature from birth, with or without extraskeletal manifestations, should include CHH-AD as a differential diagnosis. LESSONS SUBSECTIONS: Clinical suspicion is the most important and RMRP sequencing should be considered for the diagnosis of CHH-AD.

Ruxolitinib Improves Immune-Dysregulation Features but not Epigenetic Abnormality in a Patient with STAT1 GOF.

PURPOSE: Patients with STAT1 gain-of-function (GOF) mutations often exhibit autoimmune features. The JAK1/2 inhibitor ruxolitinib can be administered to alleviate autoimmune symptoms; however, it is unclear how immune cells are molecularly changed by ruxolitinib treatment. Then, we aimed to investigate the trnscriptional and epigenetic status of immune cells before and after ruxolitinib treatment in a patient with STAT1 GOF. METHODS: A patient with a heterozygous STAT1 GOF variant (p.Ala267Val), exhibiting autoimmune features, was treated with ruxolitinib, and peripheral blood mononuclear cells (PBMCs) were longitudinally collected. PBMCs were transcriptionally analyzed by single-cell cellular indexing of the transcriptomes and epitopes by sequencing (CITE-seq), and epigenetically analyzed by assay of transposase-accessible chromatin sequencing (ATAC-seq). RESULTS: CITE-seq analysis revealed that before treatment, the patient's PBMCs exhibited aberrantly activated inflammatory features, especially IFN-related features. In particular, monocytes showed high expression levels of a subset of IFN-stimulated genes (ISGs). Ruxolitinib treatment substantially downregulated aberrantly overexpressed ISGs, and improved autoimmune features. However, epigenetic analysis demonstrated that genetic regions of ISGs-e.g., STAT1, IRF1, MX1, and OAS1-were highly accessible even after ruxolitinib treatment. When ruxolitinib was temporarily discontinued, the patient's autoimmune features were aggravated, which is in line with sustained epigenetic abnormality. CONCLUSIONS: In a patient with STAT1 GOF, ruxolitinib treatment improved autoimmune features and downregulated aberrantly overexpressed ISGs, but did not correct epigenetic abnormality of ISGs.

The Impact of Pretransplant Respiratory Virus Detection on Posttransplant Outcomes in Children Undergoing Hematopoietic Cell Transplantation.

BACKGROUND: Pretransplant respiratory virus (RV) infections have been associated with negative transplant outcomes in adult hematopoietic cell transplantation (HCT) recipients. In the era of HCT delay because of high-risk RVs, we examined the impact of pretransplant RV detection on transplant outcomes in pediatric HCT recipients. METHODS: This retrospective cohort study included pediatric myeloablative allogeneic HCT recipients from 2010 to 2019. All patients were screened for RV at least once within 90 days before HCT using reverse transcriptase polymerase chain reaction (PCR), regardless of symptoms. Posttransplant outcomes included days alive and out of hospital and progression to lower respiratory tract infection (LRTI). RESULTS: Among 310 patients, 134 had an RV detected in the 90 days before HCT. In univariable analysis, transplant factors including younger age, total body irradiation, umbilical cord blood transplantation, lymphocyte count <100/mm3, HCT comorbidity index score ≥3, and viral factors including symptomatic infection, human rhinovirus as a virus type, and symptomatic pretransplant upper respiratory tract infection were associated with fewer days alive and out of hospital. In multivariable analysis, transplant factors remained significant, but not viral factors. There was a higher incidence of progression to posttransplant LRTI with the same pretransplant RV if the last positive PCR before HCT was ≤30 days compared with >30 days (P = .007). CONCLUSIONS: In the setting of recommending HCT delay for high-risk RVs, symptomatic upper respiratory tract infection, including human rhinovirus infections, may lead to increased duration of hospitalization and early progression to LRTI when transplantation is performed within 30 days of the last positive PCR test.

Performance evaluation of the SMG HHV-6 Q Real-Time PCR Kit for quantitative detection and differentiation of human herpesvirus 6A and 6B.

The aim of this study was to compare the performance of the newly developed SMG HHV-6 Q Real-Time PCR Kit (SMG assay) with the RealStar HHV-6 PCR Kit (RealStar assay). The analytical sensitivity and specificity, linearity, and precision of the SMG assay were evaluated. The clinical performance of the SMG assay was assessed and compared with that of the RealStar assay using 207 clinical specimens (HHV-6A positive, n = 51; HHV-6B positive, n = 64; HHV-6A/B negative, n = 92). The limit of detection of the SMG assay was 2.92 log10 copies/mL for HHV-6A DNA and 2.88 log10 copies/mL for HHV-6B DNA. The linear range was determined to be 3.40-9.00 log10 copies/mL for both viruses. Intra- and inter-assay variability were below 5% at concentrations ranging from 4 to 9 log10 copies/mL. No cross-reactivity was observed with the 25 microorganisms included in the specificity panel. The clinical sensitivity and specificity of the SMG and RealStar assays compared to in-house polymerase chain reaction and sequencing were as follows: SMG assay, 98.0% and 100% for HHV-6A DNA, respectively, and 96.9% and 100% for HHV-6B DNA, respectively; RealStar assay, 98.0% and 100% for HHV-6A DNA, respectively, and 90.6% and 100% for HHV-6B DNA, respectively. The correlation coefficients between viral loads measured by the two assays were 0.948 and 0.975, with mean differences of 0.62 and 0.32 log10 copies/mL for HHV-6A and HHV-6B DNA, respectively. These results demonstrate that the SMG assay is a sensitive and reliable tool for the quantitative detection and differentiation of HHV-6A and HHV-6B DNA.IMPORTANCEQuantitative real-time PCR (qPCR) that can distinguish between HHV-6A and HHV-6B DNA is recommended for diagnosis of active infection. The SMG HHV-6 Q Real-Time PCR Kit (SMG assay) is a newly developed qPCR assay that can differentiate between HHV-6A and HHV-6B DNA; however, little is known about its performance. In this study, we assessed the performance of the SMG assay and compared it with that of a commercially available qPCR assay, the RealStar HHV-6 PCR Kit (RealStar assay). The SMG assay demonstrated excellent analytical sensitivity and specificity, precision, and linearity. Furthermore, the viral loads measured by the SMG assay were highly correlated with those measured by the RealStar assay. Our results suggest that the SMG assay is a useful diagnostic tool for quantitative detection and differentiation of HHV-6A and HHV-6B DNA.

A phase 3, single-arm, open-label study to evaluate the safety, tolerability, and immunogenicity of a 15-valent pneumococcal conjugate vaccine, V114, in a 3+1 regimen in healthy infants in South Korea (PNEU-PED-KOR).

There is an ongoing burden of pneumococcal disease in children despite the use of pneumococcal conjugate vaccines (PCVs). This phase 3, open-label, single-arm, multisite, descriptive study was designed to evaluate the safety and immunogenicity of a 3 + 1 regimen of V114 (VAXNEUVANCE™), a 15-valent PCV, in South Korean infants and toddlers. Adverse events (AEs) were reported for 14 d following any vaccination, and throughout the study period for serious AEs. Serotype-specific immunoglobulin G (IgG) response rates (proportion of participants meeting an IgG threshold value of ≥0.35 µg/mL) and geometric mean concentrations (GMCs) for the 15 serotypes at 30 d postdose 3 (PD3) and at 30 d postdose 4 (PD4) were evaluated as endpoints. Healthy infants enrolled at 42-90 d after birth were vaccinated with V114 (N = 57). The most commonly reported AEs were those solicited in the trial. The majority of reported AEs were transient and of mild or moderate intensity. Few serious AEs were reported; none were vaccine related. No participants died nor discontinued the study vaccine because of an AE. V114 was immunogenic for all 15 serotypes contained in the vaccine, as assessed by IgG response rates at 30 d PD3 and IgG GMCs at 30 d PD3 and at 30 d PD4. V114 was well tolerated and immunogenic when administered as a 3 + 1 regimen in healthy South Korean infants and toddlers.

Despite the use of pneumococcal vaccines, the burden of pneumococcal disease in children persists. V114, a 15-valent pneumococcal conjugate vaccine, was immunogenic and well-tolerated in healthy South Korean infants and toddlers.

A Report on a Nationwide Surveillance System for Pediatric Acute Hepatitis of Unknown Etiology in Korea.

BACKGROUND: Several cases of pediatric acute hepatitis of unknown etiology related to adenoviral infections have been reported in Europe since January 2022. The aim of this study was to compare the incidence, severity, possible etiology, and prognosis of the disease with those in the past in Korea. METHODS: The surveillance group collected data between May and November 2022 using a surveillance system. Acute hepatitis of unknown etiology was defined in patients aged < 16 years with a serum transaminase level > 500 IU/L, not due to hepatitis A-E or other underlying causes. For comparison, data from 18 university hospitals were retrospectively collected as a control group between January 2021 and April 2022. RESULTS: We enrolled 270 patients (mean age, 5 years). The most common symptom was fever. However, the incidence was similar between 2021 and 2022. Liver function test results, number of patients with acute liver failure (ALF), liver transplantation (LT), death, and adenovirus detection rates did not differ between the two groups. None of the adenovirus-positive patients in either group experienced ALF, LT, or death. In the surveillance group, adenovirus-associated virus-2 was detected in four patients, one of whom underwent LT. Patients with an unknown etiology showed significantly higher bilirubin levels, a lower platelet count, and a higher LT rate than patients with a possible etiology. CONCLUSION: The incidence of pediatric acute hepatitis of unknown etiology and adenovirus detection rate have not increased in Korea.

Susceptibility to Fosfomycin and Nitrofurantoin of ESBL-Positive Escherichia coli and Klebsiella pneumoniae Isolated From Urine of Pediatric Patients.

BACKGROUND: Pediatric urinary tract infection (UTI) caused by extended-spectrum ß-lactamase (ESBL)-positive gram-negative bacilli (GNB) has limited options for oral antibiotic treatment. The purpose of this study was to investigate the susceptibility of ESBL-positive Escherichia coli and Klebsiella pneumoniae isolates from pediatric urine samples to two oral antibiotics (fosfomycin and nitrofurantoin). METHODS: From November 2020 to April 2022, ESBL-positive E. coli and K. pneumoniae isolates from urine samples were collected at Samsung Medical Center, Seoul, Korea. Patients over 18 years of age or with malignancy were excluded. For repeated isolates from the same patient, only the first isolate was tested. Minimum inhibitory concentrations (MICs) were measured using agar (fosfomycin) or broth (nitrofurantoin) dilution methods. MIC50 and MIC90 were measured for fosfomycin and nitrofurantoin in both E. coli and K. pneumoniae. RESULTS: There were 117 isolates from 117 patients, with a median age of 7 months (range, 0.0-18.5 years). Among 117 isolates, 92.3% (108/117) were E. coli and 7.7% (9/117) were K. pneumoniae. Isolates from the pediatric intensive care unit (PICU) and general ward (GW) was 11.1% (13/117) and 88.9% (104/117), respectively. Among 108 E. coli isolates, MIC50 and MIC90 for fosfomycin were 0.5 µg/mL and 2 µg/mL, respectively. Fosfomycin susceptibility rate was 97.2% (105/108) with a breakpoint of 128 µg/mL. Fosfomycin susceptibility rate was significantly lower in PICU isolates than in GW isolates (81.8% vs. 99.0%, P = 0.027). For nitrofurantoin, both the MIC50 and MIC90 were 16 µg/mL. Nitrofurantoin susceptibility rate was 96.3% (104/108) with a breakpoint of 64 µg/mL based on Clinical and Laboratory Standards Institute guidelines. Among the nine K. pneumoniae isolates, the MIC50 and MIC90 for fosfomycin was 2 µg/mL and 32 µg/mL, respectively. MIC50 and MIC90 for nitrofurantoin were 64 µg/mL and 128 µg/mL, respectively. CONCLUSION: For uncomplicated UTI caused by ESBL-positive GNB in Korean children, treatment with fosfomycin and nitrofurantoin for E. coli infections can be considered as an effective oral therapy option.

Complications of the Central Nervous System in Pediatric Patients With Common Cold Coronavirus Infection During 2014-2019.

BACKGROUND: In pediatric patients, the common cold coronavirus (ccCoV) usually causes mild respiratory illness. There are reports of coronavirus causing central nervous system (CNS) infection in experimental animal models. Some immunocompromised patients have also been reported to have fatal CNS infections with ccCoV. The aim of this study was to investigate the clinical characteristics of CNS complications related to ccCoV infection. METHODS: From January 2014 to December 2019, a retrospective analysis was performed of medical records from hospitalized patients under 19 years of age whose ccCoV was detected through polymerase chain reaction in respiratory specimens. The CNS complications were defined as clinically diagnosed seizure, meningitis, encephalopathy, and encephalitis. RESULTS: A total of 436 samples from 420 patients were detected as ccCoV. Among the 420 patients, 269 patients were immunocompetent and 151 patients were immunocompromised. The most common type of ccCoV was OC43 (52% in immunocompetent, 37% in immunocompromised). CNS complications were observed in 9.4% (41/436). The most common type of CNS complication was the fever-provoked seizure under pre-existing neurologic disease (42% in immunocompetent and 60% in immunocompromised patients). Among patients with CNS complications, two immunocompetent patients required intensive care unit admission due to encephalitis. Three patients without underlying neurological disease started anti-seizure medications for the first time at this admission. There was no death related to ccCoV infection. CONCLUSION: ccCoV infection may cause severe clinical manifestations such as CNS complications or neurologic sequelae, even in previously healthy children.

False-positive Aspergillus galactomannan immunoassay in the glucose component of total parenteral nutrition products.

IMPORTANCE: This manuscript describes an occurrence of false-positive GM tests in patients receiving TPN products from a manufacturer who had recently changed the supplier of the glucose component. We describe the clinical presentation of nine false-positive cases and the results of serologic and microbiological investigations of the TPN products suspected of contamination with GM. Attempts to detect GM in parenteral nutrition products were made since the detection of GM in sodium gluconate-containing solutions in 2007, but none of them identified the source of elevated GM indexes in TPN products. However, the present study demonstrated that the glucose component of the TPN products contained a high level of GM antigen, which caused false-positive GM assay results. The source of GM was glucoamylase, which was derived from A. niger in the manufacturing process. Physicians and clinical microbiology laboratories should be aware of this issue to improve interpretation and patient care.

Effective vaccination strategies to control COVID-19 in Korea: a modeling study.

OBJECTIVES: In Korea, as immunity levels of the coronavirus disease 2019 (COVID-19) in the population acquired through previous infections and vaccinations have decreased, booster vaccinations have emerged as a necessary measure to control new outbreaks. The objective of this study was to identify the most suitable vaccination strategy for controlling the surge in COVID-19 cases. METHODS: A mathematical model was developed to concurrently evaluate the immunity levels induced by vaccines and infections. This model was then employed to investigate the potential for future resurgence and the possibility of control through the use of vaccines and antivirals. RESULTS: As of May 11, 2023, if the current epidemic trend persists without further vaccination efforts, a peak in resurgence is anticipated to occur around mid-October of the same year. Under the most favorable circumstances, the peak number of severely hospitalized patients could be reduced by 43% (n=480) compared to the scenario without vaccine intervention (n=849). Depending on outbreak trends and vaccination strategies, the best timing for vaccination in terms of minimizing this peak varies from May 2023 to August 2023. CONCLUSIONS: Our findings suggest that if the epidemic persist, the best timing for administering vaccinations would need to be earlier than currently outlined in the Korean plan. It is imperative to continue monitoring outbreak trends, as this is key to determining the best vaccination timing in order to manage potential future surges.

Loop-mediated isothermal amplification assay for screening congenital cytomegalovirus infection in newborns.

Congenital cytomegalovirus (CMV) infection is a common cause of sensorineural hearing loss and neurodevelopmental impairment in newborns. However, congenital CMV infection cannot be diagnosed using samples collected more than 3 weeks after birth because testing after this time cannot distinguish between congenital infection and postnatal infection. Herein, we developed a robust loop-mediated isothermal amplification (LAMP) assay for the large-scale screening of newborns for congenital CMV infection. In contrast to conventional quantitative polymerase chain reaction (qPCR), which detects CMV within a dynamic range of 1.0 × 106 to 1.0 × 102 copies/µL, our quantitative LAMP assay (qLAMP) detects CMV within a dynamic range of 1.1 × 108 to 1.1 × 103 copies/µL. Moreover, the turnaround time for obtaining results following DNA extraction is 90 min in qPCR but only 15 min in qLamp. The colorimetric LAMP assay can also detect CMV down to 1.1 × 103 copies/µL within 30 min, irrespective of the type of heat source. Our LAMP assay can be utilized in central laboratories as an alternative to conventional qPCR for quantitative CMV detection, or for point-of-care testing in low-resource environments, such as developing countries, via colorimetric naked-eye detection. KEY POINTS: • LAMP assay enables large-scale screening of newborns for congenital CMV infection. • LAMP allows colorimetric or quantitative detection of congenital CMV infection. • LAMP assay can be used as a point-of-care testing tool in low-resource environments.

The Multifaceted Clinical Characteristics of Congenital Cytomegalovirus Infection: From Pregnancy to Long-Term Outcomes.

BACKGROUND: The aim of this study was to capture multifaceted clinical characteristics of congenital cytomegalovirus (CMV) infection from diagnosis to treatment using a multidisciplinary approach including obstetrics, pediatrics, pathology, and otorhinolaryngology-head and neck surgery. METHODS: This is a retrospective study including 30 consecutive cases of congenital CMV infection that were diagnosed at a single tertiary hospital located in Seoul, Korea from January 2009 to December 2020. Congenital CMV infection was defined as a positive result by polymerase chain reaction from urine, saliva or cerebrospinal fluid or positive CMV IgM from neonatal blood sampled within 3 weeks after birth. All cases were analyzed with respect to whole clinical characteristics from diagnosis to treatment of congenital CMV by a multidisciplinary approach including prenatal sonographic findings, maternal immune status regarding CMV infection, detailed placental pathology, neonatal clinical manifestation, auditory brainstem response test, and antiviral treatment (ganciclovir or valganciclovir). Long-term outcomes including developmental delay and hearing loss were also investigated. RESULTS: The total number of births during the study period in our institution was 19,385, with the prevalence of congenital infection estimated to be 0.15%. Among 30 cases of congenital CMV, the median gestational age at delivery was 32.2 weeks [range, 22.6-40.0] and 66.7% of these infants were delivered preterm at less than 37 weeks. Suspected fetal growth restriction was the most common prenatal ultrasound finding (50%) followed by ventriculomegaly (17.9%) and abnormal placenta (17.9%), defined as thick placenta with calcification. No abnormal findings on ultrasound examination were observed in one-third of births. Maternal CMV serology tests were conducted in only 8 cases, and one case each of positive and equivocal IgM were found. The most common placental pathologic findings were chronic villitis (66.7%) and calcification (63.0%), whereas viral inclusions were identified in only 22.2%. The most common neonatal manifestations were jaundice (58.6%) followed by elevation of aspartate aminotransferase (55.2%) and thrombocytopenia (51.7%). After excluding cases for which long-term outcomes were unavailable due to death (n = 4) or subsequent follow up loss (n = 3), developmental delay was confirmed in 43.5% of infants (10/23), and hearing loss was confirmed in 42.9% (9/21) during the follow-up period. In our cohort, 56.7% (17/30) of neonates were treated for congenital CMV with ganciclovir or valganciclovir. CONCLUSION: Our data show that prenatal findings including maternal serologic tests and ultrasound have limited ability to detect congenital CMV in Korea. Given that CMV is associated with high rates of developmental delay and hearing loss in infants, there is an urgent need to develop specific strategies for the definite diagnosis of congenital CMV infection during the perinatal period by a multidisciplinary approach to decrease the risks of neurologic impairment and hearing loss through early antiviral treatment.

COVID-19 Vaccination Status Among Korean Pediatric Population With Comorbidities.

The pediatric population with comorbidities is a high-risk group for severe coronavirus disease 2019 (COVID-19). As of January 2023, the COVID-19 vaccination rate for at least two doses among Korean children 5-11 years is low at 1.1%. We summarized the COVID-19 vaccination status for the pediatric population (5-17 years) with comorbidities through July 2022 using the National Health Insurance Service database. Pediatric patients with comorbidities had higher vaccination rates than the general pediatric population (2.4% vs. 1.1% in 5-11-year-olds [P < 0.001], 76.5% vs. 66.1% in 12-17-year-olds [P < 0.001]). However, there were substantial differences according to comorbidity category, and the 2-dose vaccination rate was lowest among children with immunodeficiency in all age groups (1.1% in 5-11-year-olds, 51.2% in 12-17-year-olds). The COVID-19 vaccination rate among Korean children has remained stagnant at a low proportion despite ongoing outreach. Thus, more proactive strategies are needed alongside continuous surveillance.

Change in Severity and Clinical Manifestation of MIS-C Over SARS-CoV-2 Variant Outbreaks in Korea.

BACKGROUND: There is difference in the incidence of multi-system inflammatory syndrome in children (MIS-C) in patients with different variants of severe acute respiratory syndrome coronavirus 2, however, little is known about the epidemiology in Asian countries. We investigated and compared the epidemiology of the MIS-C during omicron-dominant period with that of previous periods in South Korea. METHODS: We obtained clinical, epidemiological and laboratory data on MIS-C cases from national MIS-C surveillance in South Korea. We defined pre-delta period as January 2020-May 2021; delta period as June 2021-December 2021; and omicron period as January 2022-April 2022. We describe the clinical characteristics and outcomes of MIS-C patients by period. RESULTS: A total of 91 cases were assessed to be MIS-C cases. Number of MIS-C cases have increased from six cases during pre-delta period to 66 cases during omicron period, while the incidence rate (the number of MIS-C cases per 100,000 cases of reported coronavirus disease 2019) has decreased from 38.5 cases per 100,000 (95% confidence interval [CI], 14.1-83.9) during pre-delta period to 1.6 cases per 100,000 (95% CI, 1.2-2.0) during omicron periods. During pre-delta period, 66.7% and 100% had hypotension and gastrointestinal involvement, respectively; while during omicron period, 12.1% and 6.1% had such clinical manifestations. Fifty percent of pre-delta MIS-C patients were taken intensive care unit (ICU) cares, while 10.6% of patients during omicron periods were in ICUs. CONCLUSION: Omicron period were associated with less severe clinical manifestation compared to pre-delta and delta periods. Although incidence rate of MIS-C was lower for the omicron period than pre-delta and delta periods, number of patients reported with MIS-C may pose a substantial clinical burden.

Twenty-Five Year Trend Change in the Etiology of Pediatric Invasive Bacterial Infections in Korea, 1996-2020.

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic has contributed to the change in the epidemiology of many infectious diseases. This study aimed to establish the pre-pandemic epidemiology of pediatric invasive bacterial infection (IBI). METHODS: A retrospective multicenter-based surveillance for pediatric IBIs has been maintained from 1996 to 2020 in Korea. IBIs caused by eight bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pyogenes, Listeria monocytogenes, and Salmonella species) in immunocompetent children > 3 months of age were collected at 29 centers. The annual trend in the proportion of IBIs by each pathogen was analyzed. RESULTS: A total of 2,195 episodes were identified during the 25-year period between 1996 and 2020. S. pneumoniae (42.4%), S. aureus (22.1%), and Salmonella species (21.0%) were common in children 3 to 59 months of age. In children ≥ 5 years of age, S. aureus (58.1%), followed by Salmonella species (14.8%) and S. pneumoniae (12.2%) were common. Excluding the year 2020, there was a trend toward a decrease in the relative proportions of S. pneumoniae (rs = -0.430, P = 0.036), H. influenzae (rs = -0.922, P < 0.001), while trend toward an increase in the relative proportion of S. aureus (rs = 0.850, P < 0.001), S. agalactiae (rs = 0.615, P = 0.001), and S. pyogenes (rs = 0.554, P = 0.005). CONCLUSION: In the proportion of IBIs over a 24-year period between 1996 and 2019, we observed a decreasing trend for S. pneumoniae and H. influenzae and an increasing trend for S. aureus, S. agalactiae, and S. pyogenes in children > 3 months of age. These findings can be used as the baseline data to navigate the trend in the epidemiology of pediatric IBI in the post COVID-19 era.

Microbiologic Epidemiology of Early-onset Sepsis in Neonates Born at ≥35 0/7 Weeks' Gestation in Korea During 2009-2018.

BACKGROUND: Sepsis within the first 3 days of life remains a leading cause of neonatal mortality and morbidity. However, few studies have addressed the epidemiology of sepsis in late preterm and term neonates, particularly in Asia. We aimed to estimate the epidemiology of early-onset sepsis (EOS) in neonates born at ≥35 0/7 weeks' gestation in Korea. METHODS: A retrospective study was conducted in neonates with proven EOS born at ≥35 0/7 weeks' gestation from 2009 to 2018 at seven university hospitals. EOS was defined as identifying bacteria from a blood culture within 72 hours after birth. RESULTS: A total of 51 neonates (0.36/1,000 live births) with EOS were identified. The median duration from birth to the first positive blood culture collection was 17 hours (range, 0.2-63.9). Among the 51 neonates, 32 (63%) patients were born by vaginal delivery. The median Apgar score was 8 (range, 2-9) at 1 minute and 9 (range, 4-10) at 5 minutes. The most common pathogen was group B Streptococcus (n = 21; 41.2%), followed by coagulase-negative staphylococci (n = 7; 13.7%) and Staphylococcus aureus (n = 5, 9.8%). Forty-six (90.2%) neonates were treated with antibiotics on the first day of symptom onset, and 34 (73.9%) neonates received susceptible antibiotics. The overall 14-day case-fatality rate was 11.8%. CONCLUSION: This is the first multicenter study on the epidemiology of proven EOS in neonates born at ≥35 0/7 weeks' gestation and found that group B Streptococcus was the most common pathogen in Korea.