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Background: Respiratory syncytial virus (RSV), a highly transmissible virus, is the leading cause of lower respiratory tract infections. We examined molecular changes in the RSV genome before and after the coronavirus disease 2019 (COVID-19) pandemic in Korea, and investigated whether drug-resistant mutations were present., Methods: In this prospective, single-center study, RSV-positive respiratory samples were collected between September 2019 and December 2022. Long-read whole-genome sequencing (WGS) was performed, and the presence of known drug-resistant substitutions for palivizumab, nirsevimab, and suptavumab was investigated., Results: Overall, 288 respiratory samples were collected from 276 children. WGS data were available for 133 samples (71 and 62 samples from the pre- and post-pandemic periods, respectively). All RSV-A strains (n = 56) belonged to the GA2.3.5 (ON1) genotype, whereas all RSV-B strains (n = 77) belonged to the GB5.0.5a (BA) genotype. No significant differences in genotypes were observed between the pre- and post-pandemic periods. In addition, no notable mutations related to nirsevimab or palivizumab resistance were detected in the F gene. However, the L172Q and S173L substitutions, which are known to confer resistance to suptavumab, were present in all RSV-B samples., Conclusion: Despite the unprecedented interruption of RSV seasonality, there were no significant molecular changes in circulating RSV strains in Korea related to nirsevimab or palivizumab resistance before and after the COVID-19 pandemic. However, RSV-specific drug-resistance substitutions for suptavumab were identified., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

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., Competing Interests: The authors have no potential conflicts of interest to declare., (© 2024 The Korean Academy of Medical Sciences.)

Objectives: To assess the association of primary and third doses of vaccination with the risk of post-acute sequelae of COVID-19., Methods: This retrospective cohort study utilized a combined database of nationwide health care claims data, COVID-19 patient registry, and vaccination records from South Korea. Individuals diagnosed with COVID-19 in the Omicron variant-dominant period of January-March 2022 were tracked for 30-120 days post-infection. The exposure of interest was the receipt of primary and third doses of the SARS-CoV-2 vaccine. The occurrence of 26 specific conditions in eight domains was compared using Cox regression with inverse probability of treatment weighting., Results: This study included 394 773 unvaccinated individuals and 7 604 081 individuals receiving ≥2 doses of vaccine. Compared with unvaccinated individuals, vaccination with at least two doses was associated with a reduced risk (adjusted hazard ratio; 95% CI) of several conditions, including ischaemic heart disease (0.73; 0.57-0.94), heart failure (0.55; 0.48-0.63), cardiac dysrhythmia (0.72; 0.61-0.85), cardiac arrest (0.41; 0.33-0.51), pulmonary embolism (0.66; 0.52-0.84), venous thromboembolism (0.54; 0.44-0.66), acute renal failure (0.56; 0.46-0.67), new dialysis (0.45; 0.34-0.59), chronic obstructive pulmonary disease (0.74; 0.65-0.84), acute pancreatitis (0.64; 0.51-0.80), and diabetes (0.82; 0.71-0.95). The risks of heart failure, cardiac dysrhythmias, cardiac arrest, pulmonary embolism, and new dialysis were lower in those who were vaccinated with three doses compared with those who were vaccinated with two doses., Discussion: Vaccination was associated with a decreased risk of post-acute sequelae of COVID-19, suggesting its potential role in mitigating the indirect impacts of COVID-19., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Solid organ transplant recipients (SOTRs) are at higher risk for severe infection. However, the risk for severe COVID-19 and vaccine effectiveness among SOTRs remain unclear., Methods: This retrospective study used a nationwide health care claims database and COVID-19 registry from the Republic of Korea (2020 to 2022). Adult SOTRs diagnosed with COVID-19 were matched with up to 4 non-SOTR COVID-19 patients by propensity score. Severe COVID-19 was defined as treatment with high-flow nasal cannulae, mechanical ventilation, or extracorporeal membrane oxygenation., Results: Among 6783 SOTRs with COVID-19, severe COVID-19 was reported with the highest rate in lung transplant recipients (13.16%), followed by the heart (6.30%), kidney (3.90%), and liver (2.40%). SOTRs had a higher risk of severe COVID-19 compared to non-SOTRs, and lung transplant recipients showed the highest risk (adjusted odds ratio, 18.14; 95% confidence interval [CI], 8.53-38.58). Vaccine effectiveness against severe disease among SOTRs was 47% (95% CI, 18%-65%), 64% (95% CI, 49%-75%), and 64% (95% CI, 29%-81%) for 2, 3, and 4 doses, respectively., Conclusions: SOTRs are at significantly higher risk for severe COVID-19 compared to non-SOTRs. Vaccination is effective in preventing the progression to severe COVID-19. Efforts should be made to improve vaccine uptake among SOTRs, while additional protective measures should be developed., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© 2024. The Author(s).)

Background: Infections are considered risk factors for autoimmune inflammatory rheumatic diseases (AIRDs), the incidence of which is considered to have been impacted by the COVID-19 pandemic. The impact of non-pharmaceutical interventions (NPIs) on the incidence of AIRDs and their associated health care services and medical expenses in Korea was investigated., Methods: We included all AIRD cases reported between January 2016 and February 2021 based on the National Health Insurance Service data. We evaluated changes in incidence trends for each AIRD before and after NPI implementation (Feb 2020 to Feb 2021) using segmented regression analysis. Changes in health care utilization and medical costs for each AIRD before and after NPI implementation were also investigated., Results: After NPI implementation, monthly incidence rates declined significantly by 0.205 per 1 000 000 (95% confidence interval [CI], -0.308 to -0.101, p < .001) in patients with systemic lupus erythematosus (SLE). No significant changes in the incidence of all AIRDs other than SLE were observed before and after implementation. Further, annual outpatient department visits per patient were lower during implementation for all diseases, except juvenile idiopathic arthritis (JIA). The prescription days per outpatient visit increased significantly during implementation for all diseases, except JIA and ankylosing spondylitis. During implementation, the total annual medical costs per patient tended to decrease for all diseases, except JIA and mixed connective tissue disease., Conclusion: Implementation of NPIs to contain the pandemic led to a reduction in the incidence of SLE and changed patterns of medical care utilization and treatment cost for most AIRDs., (© 2024 The Authors. International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Cytomegalovirus (CMV) is the most important opportunistic viral pathogen in solid organ transplant (SOT) recipients. The Korean guideline for the prevention of CMV infection in SOT recipients was developed jointly by the Korean Society for Infectious Diseases and the Korean Society of Transplantation. CMV serostatus of both donors and recipients should be screened before transplantation to best assess the risk of CMV infection after SOT. Seronegative recipients receiving organs from seropositive donors face the highest risk, followed by seropositive recipients. Either antiviral prophylaxis or preemptive therapy can be used to prevent CMV infection. While both strategies have been demonstrated to prevent CMV infection post-transplant, each has its own advantages and disadvantages. CMV serostatus, transplant organ, other risk factors, and practical issues should be considered for the selection of preventive measures. There is no universal viral load threshold to guide treatment in preemptive therapy. Each institution should define and validate its own threshold. Valganciclovir is the favored agent for both prophylaxis and preemptive therapy. The evaluation of CMV-specific cell-mediated immunity and the monitoring of viral load kinetics are gaining interest, but there was insufficient evidence to issue recommendations. Specific considerations on pediatric transplant recipients are included., Competing Interests: WBP is associate editor and NJK, LS-O, KRP are editorial board of Infect Chemother; however, they did not involve in the peer reviewer selection, evaluation, and decision process of this article., (Copyright © 2024 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Vaccinating young children against rotavirus (RV) is a promising preventive strategy against rotavirus gastroenteritis (RVGE). We evaluated the relative risk reduction of RVGE induced by universal vaccination in Vietnam through dynamic model analysis. We developed an age-stratified dynamic Vaccinated-Susceptible-Infectious-Recovered-Susceptible model to analyze RV transmission and assess vaccine effectiveness (VE). We assumed 3 different vaccine efficacies: 55%, 70%, and 85%. For model calibration, we used a database of patients under 5 years of age admitted to Ho Chi Minh No.1 Hospital with RVGE between January 2013 and December 2018. Assuming a vaccination rate of 95%, the number of RVGE hospitalizations after 5 years from universal RV vaccination decreased from 92,502 cases to 45,626 with 85% efficacy, to 54,576 cases with 70% efficacy, and to 63,209 cases with 55% efficacy. Additionally, RVGE hospitalizations after 10 years decreased from 177,950 to 89,517 with 85% efficacy and to 121,832 cases with 55% efficacy. The relative risk reductions of RVGE after 10 years were 49.7% with 85% efficacy, 40.6% with 70% efficacy, and 31.5% with 55% efficacy. The VE was 1.10 times (95% CI, 1.01-1.22) higher in the 4-months to 1-year-old age group than in the other age groups (P = 0.038), when applying 85% efficacy with 95% coverage. In conclusion, despite its relatively lower efficacy compared to high-income countries, RV vaccination remains an effective intervention in Southwestern Vietnam. In particular, implementing universal RV vaccination with higher coverage would result in a decrease in RVGE hospitalizations among Vietnamese children under 5 years of age., (© 2024. The Author(s).)

Purpose: Encephalitis is a heterogeneous syndrome that occurs in childhood and is not rare. However, epidemiological studies of encephalitis based on the International Encephalitis Consortium (ICS) and expert recommendations are lacking. We investigated the aetiology and prognosis of encephalitis in Korean children., Materials and Methods: This retrospective study included children aged <19 years hospitalised for encephalitis at Severance Children's Hospital between 2005 and 2020. The 2013 ICS criteria were used to diagnose encephalitis, and causality was classified according to the site from which the specimen was obtained. Neurological sequelae were categorised using the modified Rankin Scale (mRS) score., Results: In total, 551 children were included, with 7% classified as possible, 77% as probable, and 15% as proven cases. A cause was identified in 42% of the cases (n=222), with viruses being the most common (42%), followed by bacteria (38%) and autoimmune encephalitis (12%). In cases of proven/probable encephalitis (n=65), bacteria accounted for 52%, followed by viruses (25%) and autoimmune encephalitis (22%). In cases with a single pathogen, the anti-N-methyl-D-aspartate receptor autoantibody (n=14) was the most common, followed by Group B streptococcus (n=13), herpes simplex virus (n=11), enterovirus (n=4), and others. Approximately 37% of patients had severe sequelae (mRS score ≥3) at discharge, which decreased to 31% 6 months after discharge., Conclusion: This large-scale study showed that autoimmune and infectious causes accounted for a significant proportion of encephalitis in Korean children. Further studies are needed to determine whether early targeted treatment following early diagnosis leads to a favourable prognosis in these populations., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Background: Transplant recipients are immunocompromised and vulnerable to developing tuberculosis. However, active tuberculosis incidence is rapidly declining in South Korea, but the trend of tuberculosis infection among transplant recipients has not been elucidated. This study aimed to evaluate the risk of active tuberculosis after transplantation, including risk factors for tuberculosis and standardized incidence ratios, compared with that in the general population., Methods: This retrospective study was conducted based on the South Korean health insurance review and assessment database among those who underwent transplantation (62,484 recipients) between 2008 and 2020. Tuberculosis incidence was compared in recipients treated during higher- (2010-2012) and lower-disease burden (2016-2018) periods. Standardized incidence ratios were analyzed using the Korean Tuberculosis Surveillance System. The primary outcome was the number of new tuberculosis cases after transplantation., Results: Of 57,103 recipients analyzed, the overall cumulative incidence rate 1 year after transplantation was 0.8% (95% confidence interval [CI]: 0.7-0.8), significantly higher in the higher-burden period than in the lower-burden period (1.7% vs. 1.0% 3 years after transplantation, P < 0.001). Individuals who underwent allogeneic hematopoietic stem cell transplantation had the highest tuberculosis incidence, followed by those who underwent solid organ transplantation and autologous hematopoietic stem cell transplantation (P < 0.001). The overall standardized incidence ratio was 3.9 (95% CI 3.7-4.2) and was the highest in children aged 0-19 years, at 9.0 (95% CI 5.7-13.5). Male sex, older age, tuberculosis history, liver transplantation, and allogeneic hematopoietic stem cell transplantation were risk factors for tuberculosis., Conclusions: Transplant recipients are vulnerable to developing tuberculosis, possibly influenced by their immunocompromised status, solid organ transplant type, age, and community prevalence of tuberculosis. Tuberculosis prevalence by country, transplant type, and age should be considered to establish an appropriate tuberculosis prevention strategy for high-risk groups., (© 2023. The Author(s).)

Purpose: Post-transplantation lymphoproliferative disorders (PTLDs) after hematopoietic stem transplantation (HCT) or solid organ transplantation (SOT) result in poorer outcomes, including death. There are limited large cohort data on the incidence and natural course of PTLD in Asians., Materials and Methods: We investigated PTLD using Korean national health insurance claims data of 47,518 patients who underwent HCT or SOT in 2008-2020. Patient demographics, time and type of PTLD diagnosis, type of PTLD treatment, and death data were collected. We used Fine and Gray subdistribution hazard models to calculate the cumulative incidence and risk factors for PTLD., Results: During median follow-up of 5.32 years, PTLD occurred in 294 of 36,945 SOT patients (0.79%) and 235 of 10,573 HCT patients (2.22%). Cumulative incidence of PTLD were 0.49% at 1 year, 1.02% at 5 years, and 1.50% at 10 years post-transplantation. Age < 20 years (subdistribution hazard ratio [SHR] of 1.67 in age 10-19, SHR 1.51 in age 0-9), HCT (SHR 3.02), heart transplantation (SHR 2.27), and liver transplantation (SHR 1.47) were significant risk factors for PTLD. The presence of PTLD was associated with an increased risk of death (hazard ratio of 2.84). Overall, 5-year survival of PTLD patients was 68.9% (95% confidence interval, 64.9 to 73.2)., Conclusion: We observed a steady increase in PTLD over 10 years after HCT or SOT in this large cohort study. Pediatric age group, HCT, liver transplantation, and heart transplantation were suggested to be risk factors for PTLD, and PTLD was associated with a higher risk of death.

Bloodstream infection (BSI) after pediatric liver transplantation (PLT) is a common and severe complication that affects patient survival. Children with biliary atresia (BA) are at an increased risk for clinically significant infections. This study evaluated the impact of post-PLT BSI on clinical outcomes in children with BA. A total of 67 patients with BA aged <18 years who underwent PLT between April 2006 and September 2020 were analyzed and divided into two groups according to the occurrence of post-PLT BSI within 1 month (BSI vs. no BSI = 13 [19.4%] vs. 54 [80.6%]). The BSI group was significantly younger at the time of PLT and had a higher frequency of BSI at the time of PLT than the no BSI group. Early vascular complications within 3 months and reoperations were significantly more frequent in the BSI group. Univariate and multivariate analyses revealed that bacteremia within 1 month of PLT and graft-to-recipient weight ratio >4% were significantly associated with vascular complications. In conclusion, BSI after PLT is associated with increased vascular complications and reoperations. Proper control of bacterial infections and early liver transplantation before uncontrolled BSI may reduce vascular complications and unexpected reoperations in children with BA.

We present a summary of the evidence on testing for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and organ procurement from deceased donors and provide recommendations based on current clinical data and the guidelines from major transplant organizations. Because of the limited historical experience with coronavirus disease 2019 (COVID-19), certain recommendations in this document are based on theoretical rationales rather than clinical data. The recommendations in this manuscript may be subject to revision as subsequent clinical studies provide definitive evidence regarding COVID-19 in organ procurement.

Objectives: The risk of severe COVID-19 in children with a solid organ transplant (SOT) is not well established. We compare the relative risk of severe COVID-19 infection between pediatric SOT and non-SOT children., Methods: The newly constructed K-COV-N cohort (Korea Disease Control and Prevention Agency-COVID-19-National Health Insurance Service) was used. Children with COVID-19 (<18 years old) who underwent SOT between January 2008 to January 2022 were included. Non-SOT children with COVID-19 were selected in a ratio of 1:4 using propensity score matching. Three definitions of severe COVID-19 were established based on their requirement for respiratory support: severe I (requiring respiratory support above a high-flow nasal cannula or prolonged hospitalization ≥6 days), severe II (requiring any oxygen supplement), and severe III (requiring any oxygen supplement or prolonged hospitalization ≥6 days)., Results: Among 2,957,323 children with COVID-19, 206 pediatric SOT recipients (SOTRs) were identified and included in the analysis along with 803 matched non-SOT children. Most infections (96.6%) occurred during the Omicron period; no cases of mortality were reported. Pediatric SOTR had a 3.6-fold (95% confidence interval = 1.1-11.7, P = 0.03) higher risk of severe I, and a 4.9-fold (95% confidence interval = 1.6-15.0, P = 0.006) higher risk of severe III than non-SOT children. No cases of severe II occurred in the non-SOT children. Although not statistically significant, no severe COVID-19 cases were reported in the vaccinated SOT group (0.0% vs 5.7%, P = 0.09 in severe III)., Conclusion: Pediatric SOTRs have a significantly higher risk of severe COVID-19 than non-SOT children. Our findings support the need for tailored strategies for these high-risk children., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Non-pharmaceutical interventions (NPIs), such as social distancing and hand washing, have been associated with a decline in the preterm birth rate worldwide. We aimed to evaluate whether the preterm birth rate in Korea during the coronavirus disease 2019 lockdown has changed compared to that in previous years., Method: A birth registry from the Korea Statistical Information Service, which is a nationwide official database, was used to include all births claimed to have occurred between 2011 and 2020. Newborns with gestational age (GA) less than 22 weeks and birth weight less than 220 g were excluded. The pre-NPI period was designated as January 2011 to January 2020, and the NPI period was defined as February 2020 to December 2020. We assessed the effect of NPI on the incidence of prematurity per 100 births using an interrupted time-series quasi-experimental design and implementing an autoregressive integrated moving average (ARIMA) model., Results: From 2011 to 2020, a total of 3,931,974 live births were registered, among which 11,416 were excluded. Consequently, the final study population included 3,920,558 live births (both singleton and multiple births) among which 275,009 (7.0%) were preterm. The preterm birth rate was significantly higher during the NPI period (8.68%) compared to that in the pre-NPI period (6.92%) ( P  < 0.001). The ARIMA model showed that in all singleton and multiple births, except those in July (observed 9.24, expected 8.54, [95% prediction interval {PI} 8.13-8.96], percent difference 7.81%), September (observed 7.89, expected 8.35, [95% PI 7.93-8.76], percent difference -5.66%), and December (observed 9.90, expected 9.40, [95% PI 8.98-9.82], percent difference 5.2%), most observed values were within the 95% PI of the expected values and showed an increasing trend., Conclusion: In this nationwide observational study, the trend in premature birth rate did not significantly change due to NPI implementation in Korea, as it had been increasing since 2011. The trend of Korea's birth rate appears to be unaffected by the implementation of NPIs; however, further studies with a longer follow-up period are needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Lee, Park, Lee, Han, Jung, Lim, Baek, Kang, Park and Ahn.)

Inborn errors of immunity (IEI) include a variety of heterogeneous genetic disorders in which defects in the immune system lead to an increased susceptibility to infections and other complications. Accurate, prompt diagnosis of IEI is crucial for treatment plan and prognostication. In this study, clinical utility of clinical exome sequencing (CES) for diagnosis of IEI was evaluated. For 37 Korean patients with suspected symptoms, signs, or laboratory abnormalities associated with IEI, CES that covers 4,894 genes including genes related to IEI was performed. Their clinical diagnosis, clinical characteristics, family history of infection, and laboratory results, as well as detected variants, were reviewed. With CES, genetic diagnosis of IEI was made in 15 out of 37 patients (40.5%). Seventeen pathogenic variants were detected from IEI-related genes, BTK , UNC13D, STAT3 , IL2RG , IL10RA , NRAS, SH2D1A, GATA2, TET2, PRF1 , and UBA1 , of which four variants were previously unreported. Among them, somatic causative variants were identified from GATA2, TET2 , and UBA1 . In addition, we identified two patients incidentally diagnosed IEI by CES, which was performed to diagnose other diseases of patients with unrecognized IEI. Taken together, these results demonstrate the utility of CES for the diagnosis of IEI, which contributes to accurate diagnosis and proper treatments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kwon, Cho, Hahn, Oh, Won, Shin, Kang, Ahn, Lee and Choi.)

This study analyzed survey results regarding awareness of living minors' organ donation. The questionnaires focused on changes in how respondents felt about donations by living minors after eliciting the uncertainty of long-term outcomes for living donors and recipients. The respondents were categorized as minors, adults affiliated with non-medical jobs (Non-Meds), and adults affiliated with medical jobs (Meds). The rates of awareness of living organ donation were significantly different; minors at 86.2%, non-Meds at 82.0%, and Meds at 98.7% ( p < 0.001). Only 41.4% of Minors and 32.0% of Non-Meds were aware of organ donation by minors, while 70.3% of Meds were ( p < 0.001). The response rate of opposition to organ donation by minors was highest for Meds and remained the same before and after (54.4%-57.7%, p = 0.311). However, the opposition rate in Non-Meds significantly increased (32.4%-46.7%) after learning about the uncertainty of long-term outcomes ( p = 0.009). The study found that Non-Meds lacked adequate knowledge regarding organ donation by minors and their potential lethal outcomes. Their attitudes toward organ donation by minors could be changed by giving structured information. It is necessary to provide exact information and raise social awareness regarding organ donation by living minors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Choi, Lee, Lee, Cho, Ihn, Yoon, Kang, Kim, Kang and Yi.)

Background: Solid organ transplant recipients (SOTRs) are susceptible to severe coronavirus disease 2019 (COVID-19); however, immunogenicity studies of the Omicron variants per vaccination schedules are still lacking. We examined humoral immunogenicity following third-dose mRNA vaccine administration in Korean SOTRs who received primary COVID-19 vaccine series on homologous or heterologous schedules., Methods: We recruited SOTRs at Severance Hospital from October 27, 2021, to March 31, 2022. Blood samples were collected between 14 days and 5 months after the second and third mRNA vaccine (BNT162b2 or mRNA-1273) doses. SARS-CoV-2 anti-spike IgG titer was analyzed. The neutralization inhibition rate was analyzed using the surrogate neutralization assay for the wild-type, Delta, and Omicron variants., Results: No significant differences existed in the SARS-CoV-2 anti-spike IgG positivity rate between the homologous BNT162b2/BNT162b2/BNT162b2 (85%) and other heterologous groups (83% of ChAdOx1/ChAdOx1/BNT162b2, 90% of ChAdOx1/ChAdOx1/mRNA-1273, and 78% of ChAdOx1/BNT162b2/BNT162b2). No significant difference existed in the neutralization inhibition rates between the four groups for wild-type, Delta, and Omicron variants. Median neutralization inhibition rates against the Omicron variant (2-5%) were significantly lower than those against the wild-type (87-97%) and Delta (55-89%) variants (P < 0.001)., Conclusions: Regardless of the schedule, the neutralization inhibition rate against the Omicron variant was poor; therefore, additional preventive measures are required in such high-risk populations., Competing Interests: Declaration Competing of Interest The authors of this manuscript have no conflicts of interest to disclose, as described by the American Journal of Transplantation., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Limited data are available on the impact of the coronavirus disease (COVID-19) pandemic on encephalitis. Therefore, we evaluated trends in encephalitis in South Korea between 2010 and 2021 using data from the National Health Insurance Service. During the pandemic (February 2020 to 2021), the monthly incidence of encephalitis declined by 0.027 per 100 000 population (95% confidence interval [CI]: -0.055 to 0.001, p = 0.062) compared to that before the pandemic. In subgroup analysis, the estimated coefficient for level change during the pandemic in the 0-4 and 5-9 years age groups were -2.050 (95% CI: -2.972 to -1.128, p < 0.001) and -0.813 (95% CI: -1.399 to -0.227, p = 0.008), respectively. The annual incidence of encephalitis during the pandemic period significantly decreased in the 0-4 and 5-9 years age groups (incidence rate ratio: 0.34 [p = 0.007] and 0.28 [p = 0.024], respectively). The intensive care unit admission rate (39.1% vs. 58.9%, p  < 0.001) and cases of death (8.9% vs. 11.1%, p < 0.001) decreased significantly during the pandemic compared to the prepandemic. During the pandemic, the incidence of encephalitis decreased markedly in South Korea, particularly in children aged ≤9 years. In addition, there were changes in the clinical outcome of encephalitis during the COVID-19 pandemic., (© 2023 Wiley Periodicals LLC.)

Live immunization is contraindicated in patients with DiGeorge syndrome (DGS). We retrospectively investigated the occurrence of adverse events after live immunization in patients with DGS in Korea. The data of patients matching the International Classification of Disease-10 code of DGS (D82.1) at Severance Hospital Seoul, Korea, were extracted; patients without genetically diagnosed DGS were excluded. Based on T cell immunity status, the included patients were categorized into group A (CD3 < 500 or CD8 < 200 cells/mm3); group B (CD3 ≥ 500 and CD8 ≥ 200 cells/mm3); or group C (unknown). Among 94 patients, 38 (~40%, group A: 8 [21%]; group B: 30 [79%]) underwent immunological testing and 73 (~80%) received at least one live immunization (measles−mumps−rubella vaccination was most common [66/94, ~70%]). Fifty adverse events (fever [n = 29], upper respiratory infection [n = 9], diarrhea [n = 4], rash [n = 3], thrombocytopenia [n = 3], injection site pus [n = 1], and febrile convulsion [n = 1]) were observed; 13 (26%) occurred in group A, with no significant difference in incidence between groups A and B. Serious adverse events, including intensive care unit hospitalization or death, or diseases due to vaccine strains were not observed. In this study, live immunization was well tolerated by patients with partial DGS.

Purpose: To examine the risk of dental abnormalities after exposure to tetracycline and its derivatives (TCs) in Korean children., Materials and Methods: Children aged 0-17 years with a claim for prescriptions of TCs between 2002 and 2015 were identified from the Sample Research Database 2.0 of the National Health Insurance Service. Children not exposed to TCs were selected as the control group by matching sex and age (1:4). Cumulative incidence rate and relative risk of dental abnormalities after TCs exposure were investigated., Results: The 10-year cumulative incidence rate in the 0-12 years group was 3.1% [95% confidence interval (CI), 2.3-3.9]. The 10-year cumulative incidence rates were 7.0%, 1.9%, and 1.6% in the 0-7, 8-12, and 13-17 years age groups (95% CI: 4.7-9.3, 1.2-2.6, and 1.3-1.9, respectively). There was no significant difference in the risk of dental abnormalities according to TC exposure among the age groups of 0-7 years [adjusted hazard ratio (aHR)=1.0], 8-12 years (aHR=1.1), and 13-17 years (aHR=1.2)., Conclusion: Short-term exposure to TCs does not appear to increase the risk of dental abnormalities in children aged 0-7 and 0-12 years. Restrictions on the use of TCs in children aged 8-12 years, in some countries, may warrant consideration., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2022.)

Background: Infections are a major cause of morbidity, graft failure, and mortality in solid organ transplant recipients. Preventive measures have greatly reduced the burden of posttransplant infections. However, little is known about the practice patterns of infection prevention in South Korea., Methods: A questionnaire-based cross-sectional survey was conducted. The questionnaire was developed by a multidisciplinary discussion. From the Korean Network for Organ Sharing data, a list of hospitals that performed kidney, liver, heart, and lung transplantations in 2019 was selected. We invited participants to respond to the questionnaire via email from January to March 2022., Results: The response rates for each organ were as follows; 41% (31/76 hospitals) for kidney, 49% (25/51) for liver, 40% (8/20) for heart, and 89% (8/9) for lung transplantations. The median duration of antibacterial prophylaxis after transplant ranged from 5 to 7 days. Prophylaxis was commonly applied in cytomegalovirus (CMV) D+/R- recipients. For non-lung CMV R+ recipients, a preemptive strategy was the most common method. The duration of viral load monitoring for preemptive or hybrid strategies varied. All lung transplant programs used mold-active antifungal agents for a median of 6 months. An interferon-gamma release assay was most commonly used to screen for latent tuberculosis infections., Conclusions: The infection prevention protocols in most transplant programs in Korea were generally in accordance with the guidelines. However, some variability was observed regarding antibacterial prophylaxis and CMV prevention. Our results provide useful insights into practice patterns and will assist in the development of national guidelines., (Copyright © 2022 The Korean Society for Transplantation.)

Purpose: Kikuchi-Fujimoto disease (KFD) is a rare, benign, and self-limited disease, characterized by cervical lymphadenopathy and fever. Herein, we analyzed the differences in its clinical manifestations and risk factors for recurrence between children and adults., Patients and Methods: We retrospectively reviewed the medical records of patients diagnosed with KFD at a tertiary referral hospital between 2005 and 2019. Patients were divided into two groups based on their age: children (<19 years) and adults (≥19 years)., Results: During the 14-year study period, 127 patients were diagnosed with KFD. Among these, 34 (26.8%) were children and 93 (73.2%) were adults. The fever duration was longer and the frequency of myalgia was higher in adults than in children; however, no other significant symptomatic differences were noted between the two groups. Lymph node evaluation was mainly performed using ultrasound in children (61.8%) and computed tomography in adults (78.5%). Moreover, the frequency of antibiotic use was higher in children than in adults (76.5% vs 54.8%, P = 0.027). In adults, multivariable logistic regression analysis revealed anti-nuclear antibody (ANA) positivity (titer ≥1:80) as a risk factor for recurrence (odds ratio: 7.813; 95% confidence interval = 1.818-33.333; P = 0.006)., Conclusion: The clinical features of KFD in children and adults were similar; however, the preferred imaging study and frequency of antibiotic use differed significantly between the two groups. Furthermore, in adults, ANA positivity was associated with KFD recurrence. Thus, patients with KFD who present with ANA positivity at diagnosis will benefit from a regular follow-up for monitoring KFD recurrence., Competing Interests: The authors report no conflicts of interest related to this work., (© 2022 Baek et al.)

Background: Solid organ transplant recipients (SOTRs) are vulnerable to severe coronavirus disease 2019 (COVID-19) and exhibit poor antibody responses to COVID-19 vaccines. Herein, we compared the humoral immunogenicity of a mixed vaccine (ChAdOx1 nCoV-19 [ChAd]/BNT162b2 [BNT]) with that of conventional matched vaccines (mRNA, adenoviral vector [AdV-Vec]) in SOTRs., Methods: Serum samples were collected at Severance Hospital (Seoul, Korea) between September and October 2021 (14 d-5 mo after COVID-19 vaccination; V2). The severe acute respiratory syndrome coronavirus 2 antispike IgG titer (BAU/mL; ELISA) and neutralization inhibition (percentage; neutralization assay) were compared between vaccination groups overall and stratified by V2 (poststudy vaccination visit) timing., Results: Of the 464 participants, 143 (31%) received mRNA vaccines, 170 (37%) received AdV-Vec vaccines, and 151 (33%) received mixed vaccines (all ChAd/BNT). The geometric mean titer for the ChAd/BNT group was 3.2-fold higher than that of the AdV-Vec group (geometric mean ratio, 3.2; confidence interval, 1.9-5.4) but lower than that of the mRNA group (geometric mean ratio, 0.4; confidence interval, 0.2-0.7). Neutralization inhibition in the ChAd/BNT group was 32%, which was higher than that in the AdV-Vec group (21%; P < 0.001) but lower than that in the mRNA group (55%; P = 0.02). There was no difference in geometric mean titer by V2 timing (ChAd/BNT, 45 versus 31, days 14-60; mRNA, 28 versus 15, days 61-150)., Conclusions: The ChAd/BNT group showed higher humoral immunogenicity than the AdV-Vec group, with similar immunogenicity to the mRNA vaccine. Nevertheless, immunogenicity following the primary vaccination series was poor in all vaccine groups, supporting the justification for booster vaccination in SOTRs., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: This study aimed to investigate whether respiratory syncytial virus (RSV) and influenza virus (IFV) infections would occur in 2021-2022 as domestic nonpharmaceutical interventions (NPIs) are easing., Methods: Data were collected from the Korean Influenza and Respiratory Virus Monitoring System database. The weekly positivity rates of respiratory viruses and number of hospitalizations for acute respiratory infections were evaluated (January 2016-2022). The period from February 2020 to January 2022 was considered the NPI period. The autoregressive integrated moving average model and Poisson analysis were used for data analysis. Data from 14 countries/regions that reported positivity rates of RSV and IFV were also investigated., Results: Compared with the pre-NPI period, the positivity and hospitalization rates for IFV infection during 2021-2022 significantly decreased to 0.0% and 1.0%, respectively, at 0.0% and 1.2% of the predicted values, respectively. The RSV infection positivity rate in 2021-2022 was 1.8-fold higher than that in the pre-NPI period at 1.5-fold the predicted value. The hospitalization rate for RSV was 20.0% of that in the pre-NPI period at 17.6% of the predicted value. The re-emergence of RSV and IFV infections during 2020-2021 was observed in 13 and 4 countries, respectively., Conclusion: During 2021-2022, endemic transmission of the RSV, but not IFV, was observed in Korea., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Importance: Infections are proposed to be triggering factors for Kawasaki disease (KD), although its etiological factors remain unknown. Recent reports have indicated a 4- to 6-week lag between SARS-CoV-2 infection and multisystem inflammatory syndrome in children with a similar presentation to that of KD., Objective: To investigate the temporal correlation between KD and viral infections, focusing on respiratory viruses., Design, Setting, and Participants: This cohort study was conducted among individuals aged 0 to 19 years diagnosed with KD between January 2010 and September 2020 from the Korean National Health Insurance Service. Data on infectious disease outbreaks from 2016 to 2019 were collected from the Korea Disease Control and Prevention Agency, Korean Influenza and Respiratory Virus Monitoring System, Korea Enteroviruses Surveillance System, and the Enteric Pathogens Active Surveillance Network in South Korea. Data were analyzed from December 2020 to October 2021., Main Outcomes and Measures: National databases for infectious diseases were used for a time-series analysis of the correlation between viral infections and KD. The temporal correlation between infectious disease outbreaks and KD outbreaks was evaluated using the Granger causality test (G-test), which is a useful tool to estimate correlations between 2 time series of diseases based on time lags., Results: Overall, 53 424 individuals with KD were identified, including 22 510 (42.1%) females and 30 914 (57.9%) males and 44 276 individuals (82.9%) younger than 5 years. Intravenous immunoglobulin-resistant KD was identified in 9042 individuals (16.9%), and coronary artery abnormalities were identified in 384 individuals (0.7%). Of 14 infectious diseases included in the analyses, rhinovirus infection outbreaks were identified as significantly correlated at 1 to 3 months before KD outbreaks in South Korea (r = 0.3; 1 month: P < .001; 2 months: P < .001; 3 months: P < .001). Outbreaks of respiratory syncytial virus infection were identified as significantly correlated with KD outbreaks by 2 months (r = 0.5; 2 months: P < .001). Additionally, varicella outbreaks were identified as significantly correlated at 2 and 3 months before KD outbreaks (r = 0.7; 2 months: P < .001; 3 months: P < .001)., Conclusions and Relevance: In this cohort study with a time series analysis of children and youth in South Korea with KD, respiratory infections caused by rhinovirus and respiratory syncytial virus and varicella outbreaks were significantly correlated with KD at 1 to 3 months before KD outbreaks.

Background: We aimed to examine the delay in antiviral initiation in rapid antigen test (RAT) false-negative children with influenza virus infection and to explore the clinical outcomes. We additionally conducted a medical cost-benefit analysis., Methods: This single-center, retrospective study included children (aged < 10 years) with influenza-like illness (ILI), hospitalized after presenting to the emergency department during three influenza seasons (2016-2019). RAT-false-negativity was defined as RAT-negative and polymerase chain reaction-positive cases. The turnaround time to antiviral treatment (TAT) was from the time when RAT was prescribed to the time when the antiviral was administered. The medical cost analysis by scenarios was also performed., Results: A total of 1,430 patients were included, 7.5% were RAT-positive (n = 107) and 2.4% were RAT-false-negative (n = 20). The median TAT of RAT-false-negative patients was 52.8 hours, significantly longer than that of 4 hours in RAT-positive patients (19.2-100.1, P < 0.001). In the multivariable analysis, TAT of ≥ 24 hours was associated with a risk of severe influenza infection and the need for mechanical ventilation (odds ratio [OR], 6.8, P = 0.009 and OR, 16.2, P = 0.033, respectively). The medical cost varied from $11.7-187.3/ILI patient., Conclusion: Antiviral initiation was delayed in RAT-false-negative patients. Our findings support the guideline that children with influenza, suspected of having severe or progressive infection, should be treated immediately., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Non-pharmaceutical interventions (NPIs) have been widely implemented to mitigate the spread of COVID-19. We assessed the effect of NPIs on hospitalisations for pneumonia, influenza, COPD and asthma. This retrospective, ecological study compared the weekly incidence of hospitalisation for four respiratory conditions before (January 2016-January 2020) and during (February-July 2020) the implementation of NPI against COVID-19. Hospitalisations for all four respiratory conditions decreased substantially during the intervention period. The cumulative incidence of admissions for COPD and asthma was 58% and 48% of the mean incidence during the 4 preceding years, respectively., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: We investigated whether non-pharmaceutical interventions (NPIs) reduce winter-prevalent respiratory viral infections represented by a respiratory syncytial virus (RSV) and influenza virus (IFV) during the winter in Korea., Methods: The Korean Influenza and Respiratory Virus Monitoring System database was used. From January 2016 through January 2021, the weekly positivity of respiratory viruses and the weekly number of hospitalizations with acute respiratory infections were collected. The NPI period was defined as February 2020-January 2021. We analyzed whether hospitalization and sample positivity by respiratory viruses changed after NPIs. Bayesian structural time-series models and Poisson analyses were used. Data from other countries/regions reporting positive rates of RSV and IFV were also investigated., Results: Compared with the pre-NPI period, the positive rates of RSV and IFV decreased significantly to 19% and 6%, and 23% and 6% of the predicted value. Also, hospitalization significantly decreased to 9% and 8%, and 10% and 5% of the predicted value. The positive rates of IFV in 14 countries during the NPI period were almost 0, whereas sporadic outbreaks of RSV occurred in some countries., Conclusions: No RSV and IFV winter epidemics were observed during the 2020-2021 season in Korea., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Many countries have implemented nonpharmaceutical interventions (NPIs) to slow the spread of coronavirus disease 2019 (COVID-19). We aimed to determine whether NPIs led to the decline in the incidences of respiratory infections., Methods: We conducted a retrospective, ecological study using a nationwide notifiable diseases database and a respiratory virus sample surveillance collected from January 2016 through July 2020 in the Republic of Korea. Intervention period was defined as February-July 2020, when the government implemented NPIs nationwide. Observed incidences in the intervention period were compared with the predicted incidences by an autoregressive integrated moving average model and the 4-year mean cumulative incidences (CuIs) in the same months of the preintervention period., Results: Five infectious diseases met the inclusion criteria: chickenpox, mumps, invasive pneumococcal disease, scarlet fever, and pertussis. The incidences of chickenpox and mumps during the intervention period were significantly lower than the prediction model. The CuIs (95% confidence interval) of chickenpox and mumps were 36.4% (23.9-76.3%) and 63.4% (48.0-93.3%) of the predicted values. Subgroup analysis showed that the decrease in the incidence was universal for chickenpox, while mumps showed a marginal reduction among those aged <18 years, but not in adults. The incidence of respiratory viruses was significantly lower than both the predicted incidence (19.5%; 95% confidence interval, 11.8-55.4%) and the 4-year mean CuIs in the preintervention period (24.5%; P < .001)., Conclusions: The implementation of NPIs was associated with a significant reduction in the incidences of several respiratory infections in Korea., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The early detection of uveitis associated with systemic inflammatory disease in children is important for proper treatment and prognosis. However, the diagnosis may be delayed because of difficulties in childhood examinations and early minor systemic symptoms. The objective of our study was to identify the pattern of childhood uveitis and investigate the frequency and clinical features of rheumatic diseases in pediatric patients with uveitis., Methods: This retrospective observational study reviewed the medical records of children (age ≤ 18 years) with uveitis at a Korean tertiary hospital between January 2005 and December 2018. Data collected included the age at onset of uveitis, sex, anatomic location of ocular inflammation, comorbid disease (including systemic inflammatory disease), ocular complications, relevant laboratory data, and treatment. Fisher's exact test was used to compare categorical variables and the Mann-Whitney U test was used to compare continuous variables. A p-value of < 0.05 was considered statistically significant., Results: A total of 155 pediatric patients with uveitis were included in this study. The median age at diagnosis was 13.0 years (interquartile range, 9.5-16.0 years). The male-to-female ratio was 1.09. The process was unilateral in 51.6% of children. Anterior uveitis, panuveitis, intermediate uveitis, and posterior uveitis represented 51.6, 26.5, 6.5, and 1.9% of the cases, respectively. Idiopathic uveitis (65.2%) was the most frequent type of uveitis. Systemic rheumatic disease associations were responsible for 28.4% of the cases, among which juvenile idiopathic arthritis (JIA) was the most frequent cause (14.8%). Human leukocyte antigen (HLA)-B27 and antinuclear antibody (ANA) positive rates were significantly higher in patients with JIA than in those with idiopathic uveitis (p = 0.006 and p = 0.007, respectively)., Conclusions: Approximately one-third of children with uveitis in Korea have a systemic rheumatic disease, of which JIA accounts for the majority of cases. HLA-B27 and ANA can serve as risk factors for JIA-associated uveitis.

Objectives: Rotavirus (RV) genotypes vary geographically, and this can affect vaccine effectiveness (VE). This study investigated the genotype distribution of RV and explored VE before introducing the RV vaccine to the national immunization programme in Vietnam., Methods: This hospital-based surveillance study was conducted at Children's Hospital 1, Ho Chi Minh City in 2013-2018. Stool samples and relevant data, including vaccination history, were collected from children aged <5 years who were hospitalized with gastroenteritis. RV was detected using enzyme immunoassays and then genotyped. Children aged ≥6 months were included in the VE analysis., Results: Overall, 5176 children were included in this study. RV was detected in 2421 children (46.8%). RV positivity decreased over the study period and was associated with age, seasonality, location and previous vaccination. Among 1105 RV-positive samples, G3P[8] was the most prevalent genotype (43.1%), followed by G8P[8] (19.7%), G1P[8] (12.9%) and G2P[4] (12.9%). Overall VE was 69.7% [95% confidence interval (CI) 53.3-80.6%] in fully vaccinated children and 58.6% (95% CI 44.1-69.4%) in children who had received at least one dose of RV vaccine. VE was highest for G3P[8] (95% CI 75.1-84.5%) and lowest for G2P[4] (95% CI 32.4-57.2%)., Conclusions: RV remains a major cause of acute gastroenteritis requiring hospitalization in southern Vietnam. The RV vaccine is effective, but its effectiveness varies with RV genotype., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

There are very scant data on the epidemiology of primary immunodeficiency diseases (PIDs) in Korea. Here we attempted to estimate the PID epidemiology and disease burden in Korea. A systematic review was performed of studies retrieved from the PubMed, KoreaMed, and Google Scholar databases. Studies on PIDs published in Korean or English between January 2001 and November 2018 were analyzed. The number of PID patients and the healthcare costs were estimated from Health Insurance Review and Assessment Service (HIRA) Korea data for 2017. A total of 398 PID patients were identified from 101 reports. Immunodeficiencies affecting cellular and humoral immunity were reported in 11 patients, combined immunodeficiency with associated or syndromic features in 40, predominantly antibody deficiencies in 144, diseases of immune dysregulation in 58, congenital defects of phagocytes in 104, defects in the intrinsic and innate immunity in 1, auto-inflammatory disorders in 4, complement deficiencies in 36, and phenocopies of PID in none. From the HIRA reimbursement data, a total of 1,162 outpatients and 306 inpatients were treated for 8,166 and 6,149 days, respectively. In addition, reimbursement was requested for 8,200 outpatient and 1,090 inpatient cases and $1,924,000 and $4,715,000 were reimbursed in 2017, respectively. This study systematically reviewed published studies on PID and analyzed the national open data system of the HIRA to estimate the disease burden of PID, for the first time in Korea.

Immunocompromised status can result in indeterminate QuantiFERON-TB Gold In-Tube (QFT-GIT) results, but the association of indeterminate results with immunocompetent status in children is unknown. Therefore, we aimed to identify factors associated with indeterminate QFT-GIT results for immunocompetent children. We conducted a retrospective chart review of children (aged ≤ 18 years) who underwent QFT-GIT between September 2006 and July 2017 at the Severance Hospital, Seoul, South Korea. Of the 2037 QFT-GIT assays included in the present study, 7.7% yielded indeterminate QFT-GIT results. Multivariable logistic regression analysis identified younger age (OR 0.88; 95% CI 0.836-0.927; P < 0.001), elevated white blood cell (WBC) count (OR 1.066; 95% CI 1.020-1.115; P = 0.005), decreased albumin levels (OR 0.505; 95% CI 0.316-0.807; P = 0.004), and low-dose steroid therapy (< 1 mg/kg per day of prednisone or equivalent for < 2 weeks) (OR 76.146; 95% CI 8.940-648.569; P < 0.001) as significant factors influencing indeterminate results. Younger age, high WBC count, low albumin levels, and low-dose steroid therapy were associated with indeterminate QFT-GIT results. Low-dose steroid therapy had the highest OR for the indeterminate results compared to other significant risk factors. Our study suggests that screening for steroid doses is important prior to performing interferon-gamma release assays for immunocompetent children.

Background: We investigated the treatment outcomes before and after the addition of amikacin to cefepime monotherapy as an initial empirical antibiotic treatment in pediatric cancer patients with febrile neutropenia., Methods: This was a retrospective historical cohort study. The subjects were pediatric cancer patients who visited the emergency room at the Samsung Medical Center, Seoul, Korea, due to chemotherapy-induced febrile neutropenia, between January 2011 and December 2016. Since September 2014, the empirical antimicrobial treatment regimen for febrile neutropenia was changed from high-dose cefepime monotherapy to combination therapy of adding a single dose of amikacin., Results: Two hundred twenty-five bacteremia episodes in 164 patients were reported during the study period. Bacteremia caused by cefepime-resistant Gram-negative bacteria was observed in 16% of patients before September 2014 and in 21% of the patients after September 2014 (P = 0.331). Use of appropriate empirical antibiotic treatments increased from 62% to 83% following addition of amikacin to cefepime treatment (P = 0.003). The duration of fever was shorter in the cefepime plus amikacin group than in the cefepime group (22 vs. 34 hours, P = 0.014); however, rates of septic shock and pediatric intensive care unit hospitalizations were not significantly different between the 2 groups (septic shock, both 7%, P = 0.436; pediatric intensive care unit 3% vs. 1%, P = 0.647)., Conclusions: We observed no additional benefit of amikacin addition to high-dose cefepime monotherapy. Therefore, adding amikacin to cefepime monotherapy in conditions where cefepime-resistant Gram-negative bacteremia amounts to 20% or less may not be justified.

Objectives: We aimed to determine the incidence and relative risk (RR) of invasive pneumococcal disease (IPD) in patients with asplenia/hyposplenism, using a nationwide population-based database., Methods: From 2009 to 2018, all claimed cases of newly diagnosed asplenia/hyposplenism in the National Health Insurance Service in South Korea were included. The incidence and RR of IPD in asplenia/hyposplenism patients were investigated using the Korean Center for Disease Control criteria., Results: Fifty-seven IPD cases were identified among 21,376 patients with 82,748 person-years of exposure. The cumulative 8-year IPD incidence was 0.5%; 45.6% of the infections occurred within two years after an asplenia/hyposplenism diagnosis. The age-standardised incidence rate was 104.5 per 100,000 person-years (95% confidence interval [CI], 103.6-105.4). Patients aged <5 years had a 15.1-times higher risk of IPD than those aged ≥60 years (95% CI: 5.8-39.5, p < 0.0001). The RR of IPD was 32.0 times higher in patients with asplenia/hyposplenism than in the general population (95% CI, 21.7-47.0); the standardized incidence ratio was 17.9(95% CI, 11.8-26.0)., Conclusions: This large population-based study highlights the high IPD incidence rate and RR in Korean patients with asplenia/hyposplenism. Increased awareness and effective prevention strategies are needed for these high-risk populations, especially children aged <5 years., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Activated phosphoinositide 3-kinase δ syndrome (APDS)1 is caused by gain-of-function mutations in PIK3CD , which encodes the catalytic p110δ subunit of phosphoinositide 3 kinase. We describe three patients with APDS1, the first thereof in Korea. Therein, we investigated clinical manifestations of APDS1 and collected data on the efficacy and safety profile of sirolimus, a mammalian target of rapamycin inhibitor and pathway-specific targeted medicine. The same heterozygous PIK3CD mutation was detected in all three patients (E1021K). After genetic diagnosis, all patients received sirolimus and experienced an excellent response, including amelioration of lymphoproliferation and improvement of nodular mucosal lymphoid hyperplasia in the gastrointestinal tract. The median trough level of sirolimus was 5.5 ng/mL (range, 2.8-7.5) at a dose of 2.6-3.6 mg/m². Two patients who needed high-dose, short-interval, immunoglobulin-replacement treatment (IGRT) had a reduced requirement for IGRT after initiating sirolimus, and the dosing interval was extended from 2 and 3 weeks to 4 weeks. The IgG trough level after sirolimus treatment (median, 594 mg/dL; range, 332-799 mg/dL) was significantly higher than that before sirolimus treatment (median, 290 mg/dL; range, 163-346 mg/dL) ( p <0.001). One episode of elevated serum creatinine with a surge of sirolimus (Patient 2) and episodes of neutropenia and oral stomatitis (Patient 1) were observed. We diagnosed the first three patients with APDS1 in Korea. Low-dose sirolimus may alleviate clinical manifestations thereof, including hypogammaglobulinemia., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2020.)

Although long-term antiviral prophylaxis is recommended to prevent varicella zoster virus (VZV) infection in seropositive recipients of allogeneic and autologous (auto-) hematopoietic cell transplantation (HCT), studies of VZV infections in pediatric auto-HCT recipients are rare. This study aimed to investigate the incidence and characteristics of VZV infection in pediatric auto-HCT recipients and explore the risk factors of VZV infection and its effect on survival outcomes. This study included all pediatric patients who underwent auto-HCT at Samsung Medical Center, Seoul, Korea, between January 1998 and December 2013. Before 2006, short-term acyclovir prophylaxis was provided until neutrophil engraftment; thereafter, routine prophylaxis was not provided. Patients who developed either herpes zoster or chickenpox within 2 years from transplantation were identified, and a chart review was performed. A total of 413 recipients and 698 auto-HCTs were included. Sixty-one episodes of VZV infections were identified in 54 patients. Fourteen cases of VZV infection (23%; 14 of 61) occurred within 30 days after auto-HCT. The cumulative incidence of the first episode of VZV infection at 2 years after transplantation was 14% (95% confidence interval [CI], 7.9% to 22.8%) in all recipients and 9% (95% CI, 1.0 to 26.6) in VZV-seronegative patients. Notably, the VZV infection rate increased with age and the VZV infection rate in patients age 15 to 19 years was almost three times higher than in patients age 0 to 4 years (28% versus 10%; P = .003). However, there was no difference in the VZV infection rate between recipients of single auto-HCT and recipients of tandem auto-HCT. Two patients died of disseminated VZV infection. VZV infection is a considerable risk in auto-HCT recipients with or without short-term prophylaxis. Universal antiviral prophylaxis might be considered, particularly in older children, regardless of VZV serologic results. To our knowledge, this is the largest study of VZV infection in pediatric auto-HCT recipients reported to date., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Coronavirus disease-2019 (COVID-19), which started in Wuhan, China, in December 2019 and declared a worldwide pandemic on March 11, 2020, is a novel infectious disease that causes respiratory illness and death. Pediatric COVID-19 accounts for a small percentage of patients and is often milder than that in adults; however, it can progress to severe disease in some cases. Even neonates can suffer from COVID-19, and children may spread the disease in the community. This review summarizes what is currently known about COVID-19 in children and adolescents.

Purpose: While there is an urgent need for diagnosis and therapeutic intervention in patients with primary immunodeficiency diseases (PIDs), current genetic tests have drawbacks. We retrospectively reviewed the usefulness of flow cytometry (FCM) as a quick tool for immunophenotyping and functional assays in patients suspected to have PIDs at a single tertiary care institute., Methods: Between January 2001 and June 2018, patients suspected of having PIDs were subjected to FCM tests, including lymphocyte subset analysis, detection of surface- or intracellular-target proteins, and functional analysis of immune cells, at Samsung Medical Center, Seoul, Korea. The genetic diagnosis was performed using Sanger or diagnostic exome sequencing., Results: Of 60 patients diagnosed with definite or probable PID according to the European Society of Immune Deficiencies criteria, 24 patients were provided with useful information about immunological dysfunction after initial FCM testing. In 10 patients, the PID diagnosis was based on abnormal findings in FCM testing without genetic tests. The FCM findings provided strong evidence for the diagnosis of severe combined immunodeficiency (n = 6), X-linked chronic granulomatous diseases (CGD) (n = 6), leukocyte adhesion deficiency type 1 (n = 3), X-linked agammaglobulinemia (n = 11), autoimmune lymphoproliferative syndrome-FASLG (n = 1), and familial hemophagocytic lymphohistiocytosis type 2 (n = 1), and probable evidence for autosomal recessive-CGD (n = 2), autosomal dominant-hyper-immunoglobulin E (IgE)-syndrome (n = 1), and STAT1 gain-of-function mutation (n = 1). In PIDs derived from PIK3CD (n = 2), LRBA (n = 2), and CTLA4 mutations (n = 3), the FCM test provided useful evidence of immune abnormalities and a tool for treatment monitoring., Conclusions: The initial application of FCM, particularly with known protein targets on immune cells, would facilitate the timely diagnosis of PIDs and thus would support clinical decisions and improve the clinical outcome., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2020 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Objectives: We investigated the incidence and characteristics of cholangitis after Kasai portoenterostomy (KPE) in patients with biliary atresia. We also examined the distribution and antimicrobial susceptibility patterns of the causative pathogens, which were isolated in sterile specimens, such as blood and ascites., Methods: A retrospective chart review was performed in patients with biliary atresia who underwent KPE at Severance Children's Hospital in Korea from 2006 to 2015. The Kaplan-Meier method was used to assess the cumulative incidence of cholangitis., Results: Among the 160 included patients, there were 494 episodes of cholangitis in 126 patients (78.8%) during the study period. The cumulative incidence of cholangitis at 1 and 5 years after KPE was 75.5% and 84.2%, respectively, and cholangitis recurred in most cases (76.2%). The cumulative incidence of culture-proven cholangitis at 1 and 5 years after KPE was 22.1% and 23.9%, respectively. Enterococcus faecium (27.7%) was the most prevalent pathogen, followed by Escherichia coli (14.9%), Enterobacter cloacae (10.6%), and Klebsiella pneumoniae (8.5%). Gram-positive isolates (n = 19) showed low susceptibility to ampicillin (42.1%) and gentamicin (66.7%), and only 38.1% of Gram-negative isolates (n = 21) were susceptible to cefotaxime., Conclusions: The present study is the largest to show the high incidence and characteristics of cholangitis after KPE in patients with biliary atresia. Enterococcus is a common pathogen of cholangitis after KPE and should be considered when choosing empiric antimicrobial therapy.

Background: The Xpert® MTB/RIF assay (Xpert; Cepheid, Sunnyvale, CA, USA) is a cartridge-based nucleic acid amplification assay for rapidly diagnosing tuberculosis and assessing antibiotic sensitivity. Although previous evidence supports the use of Xpert for diagnosing extrapulmonary tuberculosis (EPTB) in adults, information regarding the accuracy of Xpert for EPTB only in children is lacking. This meta-analysis was performed to assess the accuracy of Xpert for detecting EPTB in children., Methods: We searched the MEDLINE, EMBASE, and Cochrane Infectious Diseases Group Specialized Register from January 1, 2010 to July 16, 2019 for studies of the diagnostic performance wherein Xpert was analyzed against cultures or composite reference standards for < 18-year-old children with EPTB., Results: In only pediatric studies, 8 studies including 652 samples were selected. The pooled sensitivity and specificity of Xpert for all samples were 71% (95% CI 0.63-0.79) and 97% (95% CI 0.95-0.99), respectively. The area under the summary receiver operating characteristic (sROC) curve was 0.89. For lymph node tissues or aspirates, the pooled sensitivity and specificity of Xpert were 80% (95% CI 0.70-0.88) and 94% (95% CI 0.89-0.97), respectively; for cerebrospinal fluid (CSF), these values were 42% (95% CI 0.22-0.63) and 99% (95% CI 0.95-1.00), respectively., Conclusion: Overall, Xpert displayed high specificity but modest sensitivity across various samples for diagnosing pediatric EPTB compared to the composite reference standard. Xpert sensitivity varied with the sampling site and was especially lower in CSF samples. Positive Xpert results may be considered to indicate a presumptive case of pediatric EPTB, whereas negative test results indicate that the possibility of pediatric EPTB should not be excluded.