Etiology and Clinical Characteristics of Community-Acquired Pneumonia in Korean Children During the Pre-COVID-19 Period, 2015-2020.

BACKGROUND: There have been many epidemiologic studies on community-acquired pneumonia (CAP) among children, most of which had substantial limitations. This study investigated the etiologic distribution and clinical characteristics of CAP in Korean children for 5 years before the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A retrospective analysis of children hospitalized for CAP at 4 referral hospitals during 2015-2020 was performed. Cases in which bronchiolitis was suspected or pulmonary infiltration was not evident on chest radiography (CXR) were excluded. Viruses and atypical bacteria were defined as detected when positive in the polymerase chain reaction test performed for respiratory specimens. Serologic testing result for Mycoplasma pneumoniae was incorporated with strict interpretation. Pyogenic bacteria were included only when cultured in blood, pleural fluid, or bronchoalveolar lavage, but those cultured in endotracheal aspirate or sputum when the case was clinically evident bacterial pneumonia were also included. RESULTS: A total of 2,864 cases of suspected pneumonia were selected by diagnosis code and CXR findings. Medical chart and CXR review excluded nosocomial pneumonia and cases without evident infiltration, resulting in 517 (18.1%) CAP cases among 489 children. Regarding clinical symptoms, high fever was present in 59.4% and dyspnea in 19.9% of cases. Respiratory support was required for 29.2% of patients, including mechanical ventilation for 3.9%. Pathogens were detected in 49.9% of cases, with viruses in 32.3%, atypical bacteria in 17.8%, and pyogenic bacteria in 2.3% of cases. As single pathogens, M. pneumoniae (16.8%) and respiratory syncytial virus (RSV, 13.7%) were the most common. Parenteral ß-lactam and macrolide antibiotics were administered in 81.6% and 50.7% of cases, respectively. A total of 12 (2.3%) cases resulted in poor outcomes, including 3 deaths. CONCLUSION: M. pneumoniae and RSV were the most commonly detected pathogens of pediatric CAP, which was selected by strict clinical and radiologic criteria. It is necessary to carefully decide whether to use parenteral antibiotics based on the epidemiology and clinical features of CAP in children.

SARS-CoV-2 mRNA Vaccine Elicits Sustained T Cell Responses Against the Omicron Variant in Adolescents.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been acknowledged as an effective mean of preventing infection and hospitalization. However, the emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) has led to substantial increase in infections among children and adolescents. Vaccine-induced immunity and longevity have not been well defined in this population. Therefore, we aimed to analyze humoral and cellular immune responses against ancestral and SARS-CoV-2 variants after two shots of the BNT162b2 vaccine in healthy adolescents. Although vaccination induced a robust increase of spike-specific binding Abs and neutralizing Abs against the ancestral and SARS-CoV-2 variants, the neutralizing activity against the Omicron variant was significantly low. On the contrary, vaccine-induced memory CD4+ T cells exhibited substantial responses against both ancestral and Omicron spike proteins. Notably, CD4+ T cell responses against both ancestral and Omicron strains were preserved at 3 months after two shots of the BNT162b2 vaccine without waning. Polyfunctionality of vaccine-induced memory T cells was also preserved in response to Omicron spike protein. The present findings characterize the protective immunity of vaccination for adolescents in the era of continuous emergence of variants/subvariants.

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.

Clinical Characteristics and Outcomes of Children With SARS-CoV-2 Infection During the Delta and Omicron Variant-Dominant Periods in Korea.

BACKGROUND: Data on the clinical characteristics of pediatric patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant infection are limited. We aimed to evaluate the clinical features and outcomes of children with SARS-CoV-2 infection before and after omicron variant dominance in Korea. METHODS: A multicenter retrospective cohort study was conducted in hospitalized patients aged ≤ 18 years with laboratory-confirmed SARS-CoV-2 infection at five university hospitals in South Korea. The study periods were divided into the delta (from August 23, 2021 to January 2, 2022) and omicron (from January 30 to March 31, 2022). RESULTS: In total, 612 hospitalized patients were identified (211, delta; 401, omicron). During the omicron and delta periods, the proportions of individuals with serious illness (moderate, severe, and critical severity) were 21.2% and 11.8%, respectively (P = 0.034). Compared with the delta period, the proportions of patients with moderate illness increased significantly in the age groups of 0-4 years (14.2% vs. 3.4%) and 5-11 years (18.6% vs. 4.2%) during the omicron period. During the two periods, the proportions of patients with complex chronic diseases (delta, 16.0% vs. 4.3%, P = 0.040; omicron, 27.1% vs. 12.7%; P = 0.002), respiratory diseases except for asthma (delta, 8.0% vs. 0.0%, P = 0.013; omicron, 9.4% vs. 1.6%; P = 0.001), and neurologic diseases (delta, 28.0% vs. 3.2%, P < 0.001; omicron, 40.0% vs. 5.1%, P < 0.001) were significantly higher in patients with serious illness than in those with non-serious illness. During the delta period, the risk for serious illness was higher among patients with obesity (adjusted odds ratio [aOR], 8.18; 95% confidence interval [CI], 2.80-27.36) and neurologic diseases (aOR, 39.43; 95% CI, 6.90-268.3) and aged 12-18 years (aOR, 3.92; 95% CI, 1.46-10.85). However, the presence of neurologic disease (aOR, 9.80; 95% CI, 4.50-22.57) was the only risk factor for serious illness during the omicron period. During the omicron period, the proportions of patients with croup (11.0% vs. 0.5%) and seizures (13.2% vs. 2.8%) increased significantly compared with the delta period. CONCLUSION: Compared with the delta period, the proportions of young children and patients with complex comorbidities were higher during the omicron period in Korea. Patients with complex chronic diseases, especially neurologic diseases, had a high risk of severe coronavirus disease 2019 in the two distinct variant-dominant periods.

SARS-CoV-2-Naïve Korean Children and Adolescents Hospitalized With COVID-19 in 2021.

BACKGROUND: The risk of severe outcomes with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delta variant remains low in children and adolescents, but less is known about its effect on the SARS-CoV-2-naïve population. This study evaluated clinical manifestations and risk factors for moderate-to-critical coronavirus disease 2019 (COVID-19) in mostly SARS-CoV-2-naïve children and adolescents in 2021. METHODS: This multicenter retrospective study included patients aged 0-18 years who were hospitalized with COVID-19 at 8 referring hospitals in South Korea during the predelta-predominant and delta-predominant periods in 2021. Each case was labeled as either hospitalization with medical needs or for isolation. Severity was categorized as mild, moderate, severe, or critical with regard to pneumonia presence and illness severity. RESULTS: Among 753 cases, most (99.5%) had no prior history of COVID-19 or vaccination against COVID-19. The proportions of hospitalization with medical needs (3.5% vs. 19.7%), moderate illness (0.9% vs. 4.0%), and severe/critical illness (0.8% vs. 5.3%) increased during delta predominance. The risk of moderate-to-critical COVID-19 among hospitalizations with medical needs was higher among patients aged 12-18 years (adjusted odds ratio [aOR], 4.1; 95% confidence interval [CI], 1.5-11.8) and with obesity (aOR, 6.9; 95% CI, 2.4-19.6) but not among patients infected during delta predominance. However, children with obesity experienced more severe COVID-19 during delta predominance (aOR, 6.1; 95% CI, 1.2-29.6). CONCLUSION: Despite its similar severity among most SARS-CoV-2-naïve children and adolescents, the delta variant may affect COVID-19 severity in those with high-risk underlying medical conditions. Underlying conditions, particularly obesity, may cause severe COVID-19 in children and adolescents, warranting strong consideration for vaccinating high-risk children.

Changes in Etiology of Invasive Bacterial Infections in Infants Under 3 Months of Age in Korea, 2006-2020.

OBJECTIVES: Invasive bacterial infection (IBI) causes a significant burden in infants. In this study, we analyzed changes in epidemiology of IBI among infants in Korea. METHODS: A retrospective multicenter-based surveillance for IBIs in infants <3 months of age was performed during 2006-2020. Cases were classified as an early-onset disease (EOD) (0-6 days) or late-onset disease (LOD) (7-89 days). The temporal trend change in proportion of pathogens was analyzed. RESULTS: Among 1545 cases, the median age was 28 days (IQR: 12, 53) and EOD accounted for 17.7%. Among pathogens, S. agalactiae (40.4%), E. coli (38.5%), and S. aureus (17.8%) were the most common and attributed for 96.7%. Among EOD (n = 274), S. agalactiae (45.6%), S. aureus (31.4%), E. coli (17.2%) and L. monocytogenes (2.9%) were most common. Among LOD (n = 1274), E. coli (43.1%), S. agalactiae (39.3%), S. aureus (14.9%) and S. pneumoniae (1.3%) were most common. In the trend analysis, the proportion of S. aureus (r s = -0.850, P < 0.01) decreased significantly, while that of S. agalactiae increased (r s = 0.781, P < 0.01). CONCLUSION: During 2006-2020, among IBI in infants <3 months of age, S. agalactiae, E. coli, and S. aureus were most common and an increasing trend of S. agalactiae was observed.

Etiology and Epidemiology of Croup before and throughout the COVID-19 Pandemic, 2018-2022, South Korea.

Omicron, a recent variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently globally dominating. We reviewed the etiology and epidemiology of croup over an approximately 5-year period, with an emphasis on the recent dominance of the Omicron variant. Children less than 5 years of age seen in the emergency department with diagnosis of croup from two large national tertiary hospitals were collected for the period from January 2018 through March 2022. Viral etiologies of the patients were compared with national surveillance data upon circulating respiratory viruses in the community. A total number of 879 croup cases were recognized during the study period. The most common pathogen was SARS-CoV-2 (26.9%), followed by HRV (23.8%), PIV1 (14.6%), PIV3 (13.1%), and CoV NL63 (13.1%), among seventeen respiratory viral pathogens tested by polymerase chain reaction. The viral identification rate was significantly higher in the Omicron period, with most of the pathogens identified as SARS-CoV-2. In the Omicron period, with the exponential increase in the number of COVID-19 cases in the community, croup associated with SARS-CoV-2 significantly increased, with a high detection rate of 97.2% (35 of 36) among croup cases with pathogen identified. The etiologic and epidemiologic data before and throughout the COVID-19 pandemic indicate that the association between croup and infection with the SARS-CoV-2 Omicron variant is highly plausible.

Shift in Clinical Epidemiology of Human Parainfluenza Virus Type 3 and Respiratory Syncytial Virus B Infections in Korean Children Before and During the COVID-19 Pandemic: A Multicenter Retrospective Study.

BACKGROUND: Parainfluenza virus type 3 (PIV3) and respiratory syncytial virus (RSV) B epidemics occurred in South Korea in late 2021. We investigated epidemiological changes of PIV3 and RSV B infections in Korean children before and during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In this multicenter retrospective study, we enrolled patients aged less than 19 years with PIV3 or RSV infection in four university hospitals from January 2018 to January 2022. Demographic and clinical data were extracted from the subject's medical records and analyzed for each virus. RESULTS: A total of 652 children with PIV3 were identified including three epidemics: 216 in 2018, 260 in 2019, and 167 in 2021. Among 627 RSV B cases, 169 were identified in 2017/2018, 274 in 2019/2020, and 115 in 2021/2022. The peak circulation of PIV3 and RSV B epidemics were delayed by 6 and 2 months, respectively, in 2021, compared with those in the pre-COVID-19 period. The median age of PIV3 infections increased in 2021 (21.5 months in 2021 vs. 13.0-14.0 in 2018-2019; P < 0.001), whereas that of RSV B infections remained unchanged (3.6-4.0 months). During the COVID-19 pandemic, less frequent hospitalization rates were observed for both PIV3 and RSV B infections, but more children needed respiratory assistance for RSV B infection in 2021/2022 epidemic (32.5%) than before (14.7-19.4%, P = 0.014). CONCLUSION: We observed changes in the epidemiology and clinical presentation of PIV3 and RSV B infections in Korean children during the COVID-19 pandemic.

Epidemiology and Clinical Features of Myocarditis/Pericarditis before the Introduction of mRNA COVID-19 Vaccine in Korean Children: a Multicenter Study.

BACKGROUND: Korean health authority plans to vaccinate adolescents against coronavirus disease 2019 (COVID-19) starting high school seniors during the summer vacation of 2021. However, the myocarditis/pericarditis following COVID-19 vaccine has been reported recently in adolescents and young adults. This study was performed to answer the urgent questions about the basic epidemiology and clinical course of myocarditis/pericarditis in hospitalized patients prior to the introduction of COVID-19 vaccines in pediatric population. METHODS: A retrospective medical record analysis including frequency, clinical characteristics, etiology and outcome of myocarditis/pericarditis was conducted in 17 years and younger patients who were hospitalized in two referral hospitals in Korea between 2010 and 2019. RESULTS: Total 142 patients with myocarditis (n = 119) and/or pericarditis (n = 23) were identified. Median age was 5.4 years (interquartile range, 0.6-12.9 years; range, 11 days-17.8 years), and male was 61%. In adolescents aged 12-17 years, the male to female ratio was 3.2. Myocarditis/pericarditis occurred 0.70 per 1,000 in-patients during the study period: 0.96 (< 1 year), 0.50 (1-5 years), 0.67 (6-11 years) and 1.22 (12-17 years) per 1,000 in-patients, respectively. There was an increasing tendency for the annual frequency from 0.34 in 2010 to 1.25 per 1,000 in-patients in 2019 (P = 0.021). Among the 56 (40%) proven pathogens at admission, Mycoplasma pneumoniae (n = 11, 8%) and enterovirus (n = 10, 7%) were most common. Of the 142 patients, 99 (70%) required pediatric intensive care unit care and 10 (7%) received heart transplantation. In addition, 61 patients (61/131, 47%) without heart medication at admission needed heart medication when they were discharged. Eleven (7.7%) patients died, of which five patients were previously healthy. The median age of deceased patients was lower than the survival group (0.8 vs. 6.3 years, P = 0.014). CONCLUSION: The frequency of myocarditis/pericarditis was highest among male adolescent in-patients; however, the outcome was favorable in this group without any mortality.

Changes in the Etiology and Clinical Characteristics of Pediatric Infective Endocarditis in South Korea.

OBJECTIVE: Changes in the epidemiology, clinical manifestations, and outcomes of infective endocarditis (IE) have been reported in recent years. This study was performed to analyze changing trends in the etiology of IE in children in South Korea. STUDY DESIGN: A retrospective study of children with IE was conducted from 2 hospitals in Korea from 2004 to 2019. IE was defined according to the Modified Duke criteria. We analyzed the etiology and clinical outcome of 96 cases and compared the etiology with that during 1987-1997, as described in a previous study. RESULTS: A total of 96 cases in 89 children satisfied the modified Duke criteria. The median age was 9.5 years. Preexisting structural heart diseases were identified in 81 cases (84.4%). Ten of the 15 cases with normal heart anatomy had a history of indwelling central venous catheters and underlying noncardiac conditions. Of the 72 identified organisms, common pathogens included Staphylococcus aureus, 24 (32.9%); viridans streptococci, 22 (30.2%); coagulase-negative staphylococci, 14 (19.2%); and Candida species, 7 (9.6). Sixty-three cases (66.7%) required surgical intervention, and the overall fatality rate was 7.9%. Compared with the period of 1987-1997, an increasing trend in the proportion of staphylococci as the etiology of IE in 2004-2019 was observed (26.7% vs. 51.8%, P = 0.029). In addition, S. aureus was associated with the high rate of developing complications (P < 0.05). CONCLUSION: In South Korea, Gram-positive cocci represent 85% of all etiologic agents of IE in children with an increasing trend in the proportion of staphylococci.

Effectiveness of trivalent inactivated influenza vaccines in children during 2017-2018 season in Korea: Comparison of test-negative analysis by rapid and RT-PCR influenza tests.

OBJECTIVES: In Korea, the National Immunization Program provided trivalent inactivated influenza vaccines (IIV3) to all children aged 6-59 months during the 2017-2018 season. In this study, we aimed to evaluate the vaccine effectiveness (VE) of IIV3 in children during the 2017-2018 season. METHODS: Children aged 6-59 months who were tested for influenza for their acute respiratory illness in four hospitals during the 2017-2018 influenza season were included. We estimated the VE of IIV3 by test-negative case-control design based on the rapid influenza diagnostic test (RIDT) or reverse transcription polymerase chain reaction (RT-PCR) test results. RESULTS: A total of 4738 children were included in this study. The number of laboratory-confirmed influenza cases was 845 (17.8%), and there were 478 cases of influenza A and 362 cases of influenza B. The adjusted VE based on RT-PCR was 53.4% (95% CI, 25.3-70.5) against any influenza, 68.8% (95% CI, 38.7-84.1) against influenza A, and 29.7% (95% CI, -35.1 to 61.8) for influenza B. The adjusted VE based on RIDT was 14.8% (95% CI, -4.4 to 30.0) against any influenza, 24.2% (95% CI, 3.1-40.2) against influenza A, and -5.1% (95% CI, -42.6 to 21.4) against influenza B. Age-specific VE based on RT-PCR against any influenza was 44.1% (95% CI, -0.2 to 67.8) in children aged 6 months to 2 years and 59.3% (95% CI, 8.8-81.9) in children aged 3-<5 years. CONCLUSION: Our results suggest moderate protection (53.4%) of IIV3 against RT-PCR laboratory-confirmed influenza in children in the 2017-2018 influenza season. However, the RIDT hampered the validity to assess VE during influenza season. Caution is needed when interpreting an RIDT-based test negative design influenza VE study.

Abiotrophia defectiva as a cause of infective endocarditis with embolic complications in children.

Abiotrophia defectiva is a rare pathogen of infective endocarditis (IE) but is frequently involved in embolic complication and valvular dysfunction. IE caused by A. defectiva in children is poorly studied. This study reports four cases of A. defectiva IE in children and reviews previously reported five pediatric cases of A. defectiva IE. Most of the patients presented with a subacute course, with prolonged fever or atypical symptoms. Eight patients had embolic complications at presentation. All nine children were treated with combination antimicrobial therapy and six of them received surgical intervention. All patients recovered well without relapse. A. defectiva should be considered in children with infective endocarditis, especially in those with atypical presentations. As complications are frequent and more than half of the patients need surgical treatment, prompt diagnosis along with appropriate treatment is necessary.

Aberrant Neural Activation Underlying Idiom Comprehension in Korean Children with High Functioning Autism Spectrum Disorder.

PURPOSE: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication impairments and repetitive behaviors or restricted interests. Impaired pragmatic language comprehension is a universal feature in individuals with ASD. However, the underlying neural basis of pragmatic language is poorly understood. In the present study, we examined neural activation patterns associated with impaired pragmatic language comprehension in ASD, compared to typically developing children (TDC). MATERIALS AND METHODS: Functional magnetic resonance imaging (fMRI) was applied to 15 children with ASD and 18 TDC using the Korean pragmatic language task. RESULTS: Children with ASD were less accurate than TDC at comprehending idioms, particularly when they were required to interpret idioms with mismatched images (mismatched condition). Children with ASD also showed different patterns of neural activity than TDC in all three conditions (neutral, matched, and mismatched). Specifically, children with ASD showed decreased activation in the right inferior frontal gyrus (IFG) (Brodmann area 47) in the mismatched condition, compared with TDC (IFG; t(31)=3.17, p<0.001). CONCLUSION: These results suggest that children with ASD face difficulties in comprehending pragmatic expressions and apply different pragmatic language processes at the neural level.

Idiom Comprehension Deficits in High-Functioning Autism Spectrum Disorder Using a Korean Autism Social Language Task.

PURPOSE: High-functioning autism spectrum disorder (ASD) involves pragmatic impairment of language skills. Among numerous tasks for assessing pragmatic linguistic skills, idioms are important to evaluating high-functioning ASD. Nevertheless, no assessment tool has been developed with specific consideration of Korean culture. Therefore, we designed the Korean Autism Social Language Task (KASLAT) to test idiom comprehension in ASD. The aim of the current study was to introduce this novel psychological tool and evaluate idiom comprehension deficits in high-functioning ASD. MATERIALS AND METHODS: The participants included 42 children, ages 6-11 years, who visited our child psychiatric clinic between April 2014 and May 2015. The ASD group comprised 16 children; the attention deficit hyperactivity disorder (ADHD) group consisted of 16 children. An additional 10 normal control children who had not been diagnosed with either disorder participated in this study. Idiom comprehension ability was assessed in these three groups using the KASLAT. RESULTS: Both ASD and ADHD groups had significantly lower scores on the matched and mismatched tasks, compared to the normal control children (matched tasks mean score: ASD 11.56, ADHD 11.56, normal control 14.30; mismatched tasks mean score: ASD 6.50, ADHD 4.31, normal control 11.30). However, no significant differences were found in scores of KASLAT between the ADHD and ASD groups. CONCLUSION: These findings suggest that children with ASD exhibit greater impairment in idiom comprehension, compared to normal control children. The KASLAT may be useful in evaluating idiom comprehension ability.

A comparison of receptive-expressive language profiles between toddlers with autism spectrum disorder and developmental language delay.

PURPOSE: It is well known that expressive language impairment is commonly less severe than receptive language impairment in children with autism spectrum disorder (ASD). However, this result is based on experiments in Western countries with Western language scales. This study tries to find whether the result above is applicable for toddlers in a non-Western country; more specifically, in Korea with non-Western language scales. MATERIALS AND METHODS: The participants were 166 toddlers aged between 20 months and 50 months who visited the clinic from December 2010 to January 2013. The number of toddlers diagnosed as ASD and developmental language delay (DLD) was 103 and 63, respectively. Language development level was assessed using Sequenced Language Scale for Infants (SELSI), a Korean language scale. Using SELSI, each group was divided into 3 sub-groups. Moreover, the group difference by age was observed by dividing them into three age groups. Chi-square test and linear-by-linear association was used for analysis. RESULTS: Receptive language ability of the DLD group was superior to that of the ASD group in all age groups. However, expressive language ability in both groups showed no difference in all age groups. A greater proportion of expressive dominant type was found in ASD. The 20-29 months group in ASD showed the largest proportion of expressive language dominant type in the three age groups, suggesting that the younger the ASD toddler is, the more severe the receptive language impairment is. CONCLUSION: These findings suggest that receptive-expressive language characteristics in ASD at earlier age could be useful in the early detection of ASD.