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. Graphical

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.

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.

Therapeutics for the treatment of coronavirus disease 2019 in children and adolescents.

Coronavirus disease 2019 (COVID-19) is a mild to moderate respiratory illness in most children and adolescents, but a small proportion develop severe or critical illness. Although pediatric clinical trials for the treatment of COVID-19 are sparse, there are some available drugs for children and adolescents with severe COVID-19. This review summarizes clinical data focusing on antiviral agents and immunomodulators for COVID-19 treatment. Additionally, the current recommendations for therapeutics for children and adolescents with COVID-19 are discussed. Remdesivir is suggested for pediatric patients with COVID-19 in the following cases: children and adolescents with severe COVID-19 who need supplemental oxygen without mechanical ventilation; adolescents aged ≥12 years and weight of at least 40 kg with COVID-19 who do not require supplemental oxygen and are within 7 days of symptom onset and are at high risk of progression to severe illness. Nirmatrelvir/ritonavir is considered for adolescents aged ≥12 years and weighing at least 40 kg who do not require supplemental oxygen and are within 5 days of symptom onset and are at high risk of progression to severe disease. Corticosteroids are not recommended in children and adolescents with mild to moderate COVID-19. Corticosteroids are recommended in children and adolescents with severe to critical COVID-19.

Healthcare Workers in South Korea Maintain a SARS-CoV-2 Antibody Response Six Months After Receiving a Second Dose of the BNT162b2 mRNA Vaccine.

Background: Effective vaccines against coronavirus disease 2019 (COVID-19) are available worldwide; however, the longevity of vaccine effectiveness is not known. Objective: We performed a prospective observational study to assess the antibody response of healthcare workers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after BNT162b2 mRNA COVID-19 vaccination. Methods: SARS-CoV-2 neutralizing antibody (nAb) and spike (S) protein-IgG (S-IgG) antibody titers were examined in participants who received two doses of the BNT162b2 mRNA COVID-19 vaccine in a single center between March 1, 2021, and October 11, 2021. Antibody levels were analyzed at four times: before vaccination (visit 1), 4 weeks after the first vaccination (visit 2), 3 months after the second vaccination (visit 3), and 6 months after the second vaccination (visit 4). Results: A total of 249 healthcare workers at Jeju National University Hospital were enrolled in this study, and 982 blood samples were analyzed. The mean age was 38.1 ± 9.5 years, and 145 (58.2%) participants were females. Positive nAbs (inhibition rates ≥ 20%) were measured in 166/249 (66.7%) subjects at visit 2, 237/243 (97.5%) subjects at visit 3, and 150/237 (63.3%) subjects at visit 4. A S-IgG (≥50 AU/mL) positivity was detected in 246/249 (98.8%) subjects at visit 1, and all participants had positive S-IgG antibody levels at visits 3 and 4 after being fully vaccinated. Further analysis of S-IgG levels revealed a median quantitative antibody level of 1275.1 AU/mL (interquartile range [IQR] 755.5-2119.0) at visit 2, 2765.9 AU/mL (IQR 1809.8-4138.4) at visit 3, and 970.1 AU/mL (IQR 606.0-1495.9) at visit 4. Patient characteristics, such as age, body mass index, and comorbidity, had no relationship with nAb or S-IgG levels at any of the visits. Considering the change in antibody levels over time, both nAb and S-IgG levels at visit 4 decreased compared with the corresponding levels at visit 3. No evidence of SARS-CoV-2 infection was found among any of the participants throughout the study. Conclusions: The BNT162b2 mRNA vaccine was effective in protecting healthcare personnel working in COVID-19-related departments. While the level of S-IgG antibodies was maintained for 6 months after the second vaccination, nAb levels waned over this 6-month period, indicating the need for a booster vaccination in some healthcare workers 6 months after full vaccination. Herein, we suggest that further studies are needed to evaluate the need for an interval of booster vaccination after full vaccination.

Two adolescent cases of acute tubulointerstitial nephritis after second dose of COVID-19 mRNA vaccine.

The Food and Drug Administration (FDA) expanded the emergency use authorization for the BNT162b2 messenger RNA (mRNA) vaccine (Pfizer-BioNTech) for children aged 12-15 years on 10 May 2021. To date, less than a year has passed since vaccination against COVID-19 has been used in children and adolescents, and the overall effects and safety of these vaccines are still being assessed. The BNT162b2 vaccine originally had a favorable profile in 12-17-year-old recipients compared with older ages, and no serious adverse events had previously been reported. Despite various adverse events, the benefit of reducing the infection rate or the frequency of severe COVID-19 has been evaluated to outweigh the harm caused by COVID-19 vaccination. Additionally, several cases of sudden development of new-onset or relapsing glomerular diseases, including acute kidney injury (AKI), have been reported in adults following the BNT162b2 SARS-CoV-2 mRNA vaccine. Herein, we present two cases of adolescents who developed AKI following the second administration of the BNT162b2. These are the first pediatric cases of acute tubulointerstitial nephritis temporarily linked to SARS-CoV-2 vaccination.

Antibody Responses to SARS-CoV-2 in Children With COVID-19.

BACKGROUND: The immunologic features of children with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not clearly delineated. This study was conducted to evaluate SARS-CoV-2-specific antibody responses in children with COVID-19. METHODS: The levels of anti-spike (S) IgG, anti-SARS-CoV-2 IgG, and neutralizing antibody (NAb) were measured during various time points in children <19 years of age with COVID-19 in South Korea from February 2020 to September 2020. RESULTS: One hundred sixty-five blood samples from 114 children with COVID-19 (43.9% asymptomatic and 56.1% mildly symptomatic) were analyzed. In both asymptomatic and mildly symptomatic children, the positive rates of anti-S IgG, anti-SARS-CoV-2 IgG, and NAb were low within 7 days after onset, but they soon reached 100% 14 to <28 days after onset. In symptomatic children, the geometric mean titers (GMTs) of antibodies were all below the positive cutoff during the first 2 weeks from onset and peaked at 28 to <56 days (5.6 for anti-S IgG, 383.6 for anti-SARS-CoV-2 IgG, and 55.0 for NAb, P < .001, respectively). Antibody levels remained detectable up to 3 months after infection. The antibody GMTs during the period 14 to <56 days after symptom onset were highest in children aged 0-4 years. CONCLUSIONS: These results collectively present the humoral immune responses during SARS-CoV-2 infection in children. A further longitudinal study is needed to thoroughly understand the immune system and for effective vaccine development in children during the COVID-19 pandemic.

Expert Consensus on COVID-19 Vaccination in Korean Adolescents: A Modified Delphi Survey.

The effectiveness of coronavirus disease 2019 (COVID-19) vaccines had been shown in many studies in adult population, however, the real-world evidence in the childhood population was scarce. We aimed to organize the collective expert's opinions on adolescent vaccination against COVID-19 in Korea, therefore to guide the vaccination policy in the setting of available evidence. The Delphi panels responded that adolescents were greatly impacted by the quarantine measures, and COVID-19 is an important health problem for adolescents. Panels responded that in general, the benefits of the COVID-19 vaccine overweigh the potential risks in Korean adolescents. Continuing monitoring of available data is needed to provide the best vaccination practices in adolescents guided by the updated evidence.

Differential Impact of Nonpharmaceutical Interventions on the Epidemiology of Invasive Bacterial Infections in Children During the Coronavirus Disease 2019 Pandemic.

BACKGROUND: Invasive bacterial infection (IBI) remains a major burden of mortality and morbidity in children. As coronavirus disease 2019 (COVID-19) emerged, stringent nonpharmaceutical interventions (NPIs) were applied worldwide. This study aimed to evaluate the impact of NPIs on pediatric IBI in Korea. METHODS: From January 2018 to December 2020, surveillance for pediatric IBIs caused by 9 pathogens (S. pneumoniae, H. influenzae, N. meningitidis, S. agalactiae, S. pyogenes, S. aureus, Salmonella species, L. monocytogenes and E. coli) was performed at 22 hospitals throughout Korea. Annual incidence rates were compared before and after the COVID-19 pandemic. RESULTS: A total of 651 cases were identified and the annual incidence was 194.0 cases per 100,000 in-patients in 2018, 170.0 in 2019 and 172.4 in 2020. Most common pathogen by age group was S. agalactiae in infants < 3 months (n = 129, 46.7%), S. aureus in 3 to < 24 months (n = 35, 37.2%), Salmonella spp. in 24 to < 60 months (n = 24, 34.8%) and S. aureus in children ≥ 5 years (n = 128, 60.7%). Compared with 2018 to 2019, the incidence rate in 2020 decreased by 57% for invasive pneumococcal disease (26.6 vs. 11.5 per 100,000 in-patients, P = 0.014) and 59% for Salmonella spp. infection (22.8 vs. 9.4 per 100,000 in-patients, P = 0.018). In contrast, no significant changes were observed in invasive infections due to S. aureus, S. agalactiae and E. coli. CONCLUSIONS: The NPIs implemented during the COVID-19 pandemic reduced invasive diseases caused by S. pneumoniae and Salmonella spp. but not S. aureus, S. agalactiae and E. coli in children.

Healthcare Workers in South Korea Maintain a SARS-CoV-2 Antibody Response Six Months After Receiving a Second Dose of the BNT162b2 mRNA Vaccine

Background Effective vaccines against coronavirus disease 2019 (COVID-19) are available worldwide;however, the longevity of vaccine effectiveness is not known. Objective We performed a prospective observational study to assess the antibody response of healthcare workers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after BNT162b2 mRNA COVID-19 vaccination. Methods SARS-CoV-2 neutralizing antibody (nAb) and spike (S) protein-IgG (S-IgG) antibody titers were examined in participants who received two doses of the BNT162b2 mRNA COVID-19 vaccine in a single center between March 1, 2021, and October 11, 2021. Antibody levels were analyzed at four times: before vaccination (visit 1), 4 weeks after the first vaccination (visit 2), 3 months after the second vaccination (visit 3), and 6 months after the second vaccination (visit 4). Results A total of 249 healthcare workers at Jeju National University Hospital were enrolled in this study, and 982 blood samples were analyzed. The mean age was 38.1 ± 9.5 years, and 145 (58.2%) participants were females. Positive nAbs (inhibition rates ≥ 20%) were measured in 166/249 (66.7%) subjects at visit 2, 237/243 (97.5%) subjects at visit 3, and 150/237 (63.3%) subjects at visit 4. A S-IgG (≥50 AU/mL) positivity was detected in 246/249 (98.8%) subjects at visit 1, and all participants had positive S-IgG antibody levels at visits 3 and 4 after being fully vaccinated. Further analysis of S-IgG levels revealed a median quantitative antibody level of 1275.1 AU/mL (interquartile range [IQR] 755.5–2119.0) at visit 2, 2765.9 AU/mL (IQR 1809.8–4138.4) at visit 3, and 970.1 AU/mL (IQR 606.0–1495.9) at visit 4. Patient characteristics, such as age, body mass index, and comorbidity, had no relationship with nAb or S-IgG levels at any of the visits. Considering the change in antibody levels over time, both nAb and S-IgG levels at visit 4 decreased compared with the corresponding levels at visit 3. No evidence of SARS-CoV-2 infection was found among any of the participants throughout the study. Conclusions The BNT162b2 mRNA vaccine was effective in protecting healthcare personnel working in COVID-19-related departments. While the level of S-IgG antibodies was maintained for 6 months after the second vaccination, nAb levels waned over this 6-month period, indicating the need for a booster vaccination in some healthcare workers 6 months after full vaccination. Herein, we suggest that further studies are needed to evaluate the need for an interval of booster vaccination after full vaccination.

Risk Factors for Severe COVID-19 in Children: A Systematic Review and Meta-Analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been the most important global issue since December 2019. Although the clinical course of COVID-19 is known to be milder in children than in adults, associated hospitalizations among children have increased since the emergence of contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the achievement of a high vaccination rate in adults. Considering these global and domestic situations, we believe that risk stratification in children with COVID-19 is urgently needed for decision making regarding hospitalization priority in children infected with SARS-CoV-2 and vaccination priority against COVID-19. METHODS: This systematic review and meta-analysis was performed by comprehensively searching the PubMed, EMBASE, Scopus and KoreaMed databases through August 25, 2021. The criteria for enrollment were "severe COVID-19" as poor outcomes (intensive care unit admission, invasive mechanical ventilation, and/or death) and underlying comorbidities before SARS-CoV-2 infection. RESULTS: Among 872 screened studies, 17 articles were included in the systematic review, and 10 articles were included in the meta-analysis. Neonate (risk ratio [RR], 2.69; 95% confidence interval [CI], 1.83-3.97), prematurity in young infants (RR, 2.00; 95% CI, 1.63-2.46), obesity (RR, 1.43; 95% CI, 1.24-1.64), diabetes (RR, 2.26; 95% CI, 1.95-2.62), chronic lung disease (RR, 2.62; 95% CI, 1.71-4.00), heart disease (RR, 1.82; 95% CI, 1.58-2.09), neurologic disease (RR, 1.18; 95% CI, 1.05-1.33), and immunocompromised status (RR, 1.44; 95% CI, 1.01-2.04) were significant risk factors for severe COVID-19 in children. In the subgroup analysis, age younger than 3 months (RR, 0.26; 95% CI, 0.11-0.66), asthma (RR, 1.08; 95% CI, 0.98-1.20), and neurodevelopmental disorders (RR, 0.88; 95% CI, 0.75-1.04) were not risk factors for severe COVID-19. CONCLUSION: Children with comorbidities such as obesity, diabetes, heart disease, chronic lung diseases other than asthma, seizure disorders, and an immunocompromised status had a high prevalence of severe COVID-19. Neonate and premature infants had a high risk of severe COVID-19. Defining the high-risk group for severe COVID-19 could help to guide hospital admission and priority for vaccination against SARS-CoV-2.

COVID-19 in children across three Asian cosmopolitan regions.

ABSTRACT As another wave of COVID-19 outbreak has approached in July 2020, a larger scale COVID-19 pediatric Asian cohort summarizing the clinical observations is warranted. Children confirmed with COVID-19 infection from the Republic of Korea, the Hong Kong Special Administrative Region (HKSAR) and Wuhan, China, during their first waves of local outbreaks were included. Their clinical characteristics and the temporal sequences of the first waves of local paediatric outbreaks were compared. Four hundred and twenty three children with COVID-19 were analyzed. Wuhan had the earliest peak, followed by Korea and HKSAR. Compared with Korea and Wuhan, patients in HKSAR were significantly older (mean age: 12.9 vs. 10.8 vs. 6.6 years, p < 0.001, respectively) and had more imported cases (87.5% vs. 16.5% vs. 0%, p < 0.001, respectively). The imported cases were also older (13.4 vs. 7.6 years, p < 0.001). More cases in HKSAR were asymptomatic compared to Korea and Wuhan (45.5% vs. 22.0% vs. 20.9%, p < 0.001, respectively), and significantly more patients from Wuhan developed fever (40.6% vs. 29.7% vs. 21.6%, p=0.003, respectively). There were significantly less imported cases than domestic cases developing fever after adjusting for age and region of origin (p = 0.046). 5.4% to 10.8% of patients reported anosmia and ageusia. None developed pediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PMIS-TS). In general, adolescents were more likely to be asymptomatic and less likely to develop fever, but required longer hospital stays. In conclusion, majority patients in this pediatric Asian cohort had a mild disease. None developed PIMS-TS. Their clinical characteristics were influenced by travel history and age.

Clinical Characteristics and Viral RNA Detection in Children With Coronavirus Disease 2019 in the Republic of Korea.

Importance: There is limited information describing the full spectrum of coronavirus disease 2019 (COVID-19) and the duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA detection in children. Objective: To analyze the full clinical course and the duration of SARS-CoV-2 RNA detectability in children confirmed with COVID-19 in the Republic of Korea, where rigorous public health interventions have been implemented. Design, Setting, and Participants: This case series of children with COVID-19 was conducted in 20 hospitals and 2 nonhospital isolation facilities across the country from February 18, 2020, to March 31, 2020. Children younger than 19 years who had COVID-19 were included. Exposures: Confirmed COVID-19, detected via SARS-CoV-2 RNA in a combined nasopharyngeal and oropharyngeal swab or sputum by real-time reverse transcription-polymerase chain reaction. Main Outcomes and Measures: Clinical manifestations during the observation period, including the time and duration of symptom occurrence. The duration of SARS-CoV-2 RNA detection was also analyzed. Results: A total of 91 children with COVID-19 were included (median [range] age, 11 [0-18] years; 53 boys [58%]). Twenty children (22%) were asymptomatic during the entire observation period. Among 71 symptomatic cases, 47 children (66%) had unrecognized symptoms before diagnosis, 18 (25%) developed symptoms after diagnosis, and only 6 (9%) were diagnosed at the time of symptom onset. Twenty-two children (24%) had lower respiratory tract infections. The mean (SD) duration of the presence of SARS-CoV-2 RNA in upper respiratory samples was 17.6 (6.7) days. Virus RNA was detected for a mean (SD) of 14.1 (7.7) days in asymptomatic individuals. There was no difference in the duration of virus RNA detection between children with upper respiratory tract infections and lower respiratory tract infections (mean [SD], 18.7 [5.8] days vs 19.9 [5.6] days; P = .54). Fourteen children (15%) were treated with lopinavir-ritonavir and/or hydroxychloroquine. All recovered, without any fatal cases. Conclusions and Relevance: In this case series study, inapparent infections in children may have been associated with silent COVID-19 transmission in the community. Heightened surveillance using laboratory screening will allow detection in children with unrecognized SARS-CoV-2 infection.

Financial Burden of Hospitalization of Children with Coronavirus Disease 2019 under the National Health Insurance Service in Korea.

Coronavirus disease 2019 (COVID-19) has resulted in an ongoing pandemic; however, the socioeconomic burden of COVID-19 treatment in the pediatric population remains unclear. Thus, the aim of this study was to determine the hospitalization periods and medical costs among children with COVID-19. In total, 145 billing statements for pediatric patients receiving healthcare services because of COVID-19 from February 1, 2020 to March 31, 2020 were used. The study showed that individual treatment costs for children with COVID-19 are approximately USD 2,192 under the Korean National Health Insurance Service System. This study revealed the differences in cost among age groups, determined by the type of hospital wherein admission occurred, as a trend of increasing age, increasing hospitalization time, and increasing cost was observed. Tailored COVID-19 treatment strategies by age group may lower costs and increase the effectiveness of resource allocation.