Epidemiology of Respiratory Viruses in Korean Children Before and After the COVID-19 Pandemic: A Prospective Study From National Surveillance System.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic led to a decrease in the seasonal incidence of many respiratory viruses worldwide due to the impact of nonpharmaceutical interventions (NPIs). However, as NPI measures were relaxed, respiratory viral infections re-emerged. We aimed to characterize the epidemiology of respiratory viruses in Korean children during post-COVID-19 pandemic years compared to that before the pandemic. METHODS: A nationwide prospective ongoing surveillance study has been conducted for detection of respiratory viruses between January 2017 and June 2023. We included data on adenovirus (AdV), human bocavirus (HBoV), human coronavirus (HCoV), human metapneumovirus (HMPV), human rhinovirus (HRV), influenza virus (IFV), parainfluenza virus (PIV), and respiratory syncytial virus (RSV), which were detected in children and adolescents younger than 20 years. We analyzed the weekly detection frequency of individual viruses and the age distribution of the affected children. The study period was divided into prepandemic (2017-2019) and postpandemic (2021-2023) periods. RESULTS: A total of 19,589 and 14,068 samples were collected in the pre- and postpandemic periods, respectively. The overall detection rate of any virus throughout the study period was 63.1%, with the lowest occurring in the 2nd half of 2020 (50.6%) and the highest occurring in the 2nd half of 2021 (72.3%). Enveloped viruses (HCoV, HMPV, IFV, PIV, and RSV) almost disappeared, but nonenveloped viruses (AdV, HBoV, and HRV) were detected even during the peak of the COVID-19 pandemic. The codetection rate increased from 15.0% prepandemic to 19.1% postpandemic (P < 0.001). During the postpandemic period, a large out-of-season PIV and HMPV epidemic occurred, but the usual seasonality began to be restored in 2023. The mean age of children with each virus detected in 2023 was significantly greater than that in prepandemic years (P = 0.003 and 0.007 for AdV and HCoV, respectively; P < 0.001 for others). The mean age of children with IFV increased in 2022 (11.1 ± 5.2 years) from prepandemic years (7.9 ± 4.6 years) but decreased to 8.7 ± 4.1 years in 2023. CONCLUSION: With the relaxation of NPI measures, several seasonal respiratory viruses cocirculated with unusual seasonal epidemic patterns and were associated with increasing age of infected children.

Clinical Characteristics and Severity of Respiratory Syncytial Virus Infection in Korean Children during the Post-COVID-19 Pandemic Period.

We aimed to evaluate the clinical features of respiratory syncytial virus (RSV) infection and risk factors for severe RSV disease among Korean children in 2022/2023. A total of 235 children were identified, and 84.3% were hospitalized. Patients under 3 months and 2 years of age accounted for 20.9% and 54.5%, respectively. Pneumonia was diagnosed in 40.9% of children and bronchiolitis in 23.8%. Respiratory support and intensive care were required in 43.4% and 7.7% of patients, respectively. Haemophilus influenzae nasopharyngeal colonization and the presence of underlying disease showed a significant correlation with severity indicators. The clinical impact of RSV infection was high on infants and toddlers, even those having no underlying disease or not being indicated for palivizumab.

Community-acquired pneumonia in children: updated perspectives on its etiology, diagnosis, and treatment.

Pneumonia is a common pediatric infectious disease that is familiar to pediatricians and a major cause of hospitalization worldwide. Recent well-designed epidemiologic studies in developed countries indicated that respiratory viruses are detected in 30%-70%, atypical bacteria in 7%-17%, and pyogenic bacteria in 2%-8% of children hospitalized with community-acquired pneumonia (CAP). The etiological distribution of CAP varies widely by child age and the epidemiological season of the respiratory pathogen. Moreover, diagnostic tests, particularly for the detection of Streptococcus pneumoniae and Mycoplasma pneumoniae, the 2 major bacterial pathogens involved in pediatric CAP, have several limitations. Therefore, management and empirical antimicrobial therapy for children with CAP should be applied in a stepwise manner based on recent epidemiological, etiological, and microbiological evidence.

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.

First Detection of Enterovirus D68 in Korean Children, September 2022.

BACKGROUND: Enterovirus D68 (EV-D68) is a re-emerging pathogen that is particularly common in children and may cause asthma-like respiratory infection and acute flaccid myelitis. However, in Korea, EV-D68 has never been reported thus far. This study aimed to identify EV-D68 from nasopharyngeal aspirates (NPAs) in Korean children with a respiratory tract infection. MATERIALS AND METHODS: The EV-D68 reference strain was purchased and blindly used to assess the detection ability of three commercial and one in-house mRT-PCR kit in 2018. Then, we selected children whose specimens were positive for human rhinovirus (HRV) and/or enterovirus (EV) by Allplex mRT-PCR (Seegene, Inc., Seoul, Korea) from April to December 2022. Total RNA was extracted from NPAs, and a partial 5'-UTR gene was amplified and sequenced for the identification of HRV/EV species. Additionally, PCR targeting the VP1 gene was performed to assess EV-D68-positive NPAs, followed by sequencing. Phylogenetic analysis and comparison of amino acid sequence alignments were performed using a partial VP1 gene of our and recent international EV-D68 strains. RESULTS: Among the mRT-PCR kits tested, only the in-house kit was able to detect EV-D68 in 2018. However, we detected three EV-D68 strains among children hospitalized with fever and/or respiratory symptoms in September - December 2022 who tested positive for EV by the Allplex kit. Two of them were healthy toddlers with lower respiratory infections accompanied by new-onset wheezing but no neurologic complications. Among 34 children with lower respiratory infection who tested positive for HRV during the same period, EV-D68 was not detected. Phylogenetic analysis revealed that the first Korean EV-D68 belonged to subclade B3. Amino acid sequence alignment of international subclade B3 EV-D68 strains also showed that our strain is genetically more related to those from Europe than those from Japan. CONCLUSION: We first detected EV-D68 in three Korean children who had EV detected by the Allplex mRT-PCR kit in 2022. EV-D68 also circulated in Korea in fall 2022, but the prevalence and severity seemed to be lower than those in previous reports from other countries.

Two Years of Experience and Methodology of Korean COVID-19 Living Clinical Practice Guideline Development.

BACKGROUND: In Korea, during the early phase of the coronavirus disease 2019 (COVID-19) pandemic, we responded to the uncertainty of treatments under various conditions, consistently playing catch up with the speed of evidence updates. Therefore, there was high demand for national-level evidence-based clinical practice guidelines for clinicians in a timely manner. We developed evidence-based and updated living recommendations for clinicians through a transparent development process and multidisciplinary expert collaboration. METHODS: The National Evidence-based Healthcare Collaborating Agency (NECA) and the Korean Academy of Medical Sciences (KAMS) collaborated to develop trustworthy Korean living guidelines. The NECA-supported methodological sections and 8 professional medical societies of the KAMS worked with clinical experts, and 31 clinicians were involved annually. We developed a total of 35 clinical questions, including medications, respiratory/critical care, pediatric care, emergency care, diagnostic tests, and radiological examinations. RESULTS: An evidence-based search for treatments began in March 2021 and monthly updates were performed. It was expanded to other areas, and the search interval was organized by a steering committee owing to priority changes. Evidence synthesis and recommendation review was performed by researchers, and living recommendations were updated within 3-4 months. CONCLUSION: We provided timely recommendations on living schemes and disseminated them to the public, policymakers and various stakeholders using webpages and social media. Although the output was successful, there were some limitations. The rigor of development issues, urgent timelines for public dissemination, education for new developers, and spread of several new COVID-19 variants have worked as barriers. Therefore, we must prepare systematic processes and funding for future pandemics.

Molecular epidemiology of Acinetobacter baumannii complex causing invasive infections in Korean children during 2001-2020.

BACKGROUND: Acinetobacter baumannii (AB) has emerged as one of the most problematic pathogens affecting critically ill patients. This study aimed to investigate the longitudinal epidemiology of AB causing invasive diseases in children. METHODS: Acinetobacter spp. cultured from sterile body fluids and identified as Acinetobacter calcoaceticus-baumannii (ACB) complexes by automated systems from children aged below 19 years old were prospectively collected during 2001-2020. The discriminative partial sequence of rpoB gene was sequenced to identify the species, and sequence types (STs) were determined. Temporal changes in antimicrobial susceptibilities and STs were analyzed. RESULTS: In total, 108 non-duplicate ACB isolates were obtained from patients with invasive infections. The median age was 1.4 (interquartile range, 0.1-7.9) years, and 60.2% (n = 65) were male. Acinetobacter baumannii comprised 55.6% (n = 60) of the isolates, and the 30-day mortality was higher in patients with isolated AB than in those with non-baumannii Acinetobacter spp. (46.7% vs. 8.3%, P < 0.001). After 2010, complete genotype replacement was observed from non-CC92 genotypes to only CC92 genotypes. Carbapenem resistance rates were highest in AB CC92 (94.2%), followed by AB non-CC92 (12.5%) and non-baumannii Acinetobacter spp. (2.1%). During 2014-2017, which included clustered cases of invasive ST395, colistin resistance increased to 62.5% (n = 10/16), showing a mortality rate of 88% during this period. CONCLUSION: Complete genotype replacement of non-CC92 with CC92 genotypes was observed. AB CC92 was extensively drug-resistant, and pandrug resistance was observed depending on the ST, warranting careful monitoring.

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.

Respiratory syncytial virus infection and the need for immunization in Korea.

INTRODUCTION: Respiratory syncytial virus (RSV) infection is one of the most common causes of acute respiratory tract infections in young children and the elderly. Infants and young children aged <2 years and the elderly are at particular risk of severe infections requiring hospitalization. AREAS COVERED: This narrative review summarizes the epidemiology of RSV infection in Korea, with a particular focus on infants and the elderly, where possible, and highlights the need for effective vaccinations against RSV. Relevant papers were identified from a search of PubMed up to December 2021. EXPERT OPINION: RSV infection is associated with a significant burden of illness in infants and the elderly worldwide and accounts for a substantial number of hospital admissions due to severe lower respiratory tract infections in both of these age groups in Korea. Vaccination has the potential to reduce the burden of acute RSV-associated disease and long-term consequences such as asthma. Increased understanding of the immune response to RSV, including mucosal immunity, and the innate and adaptive immune responses is needed. Technological advances in vaccine platforms could provide better approaches for achieving a safe and effective vaccine-induced immune response.

Non-neuropsychiatric Long COVID Symptoms in Children Visiting a Pediatric Infectious Disease Clinic After an Omicron Surge.

Although much interest has emerged regarding post-COVID conditions, data on children and adolescents are limited. The prevalence of long COVID and common symptoms were analyzed in this case-control study of 274 children. Prolonged non-neuropsychiatric symptoms were more frequent in the case group (17.0% and 4.8%, P = 0.004). Abdominal pain (6.6%) was the most common long COVID symptom.

Pediatric Deaths Associated With Coronavirus Disease 2019 (COVID-19) in Korea.

As of September 3, 2022, 5,388,338 coronavirus disease 2019 (COVID-19) cases and 46 deaths (3 in 2021 and 43 in 2022) were reported in children ≤ 18 years in Korea. Cumulative confirmed cases accounted for 67.3% of the population aged ≤ 18 years and case fatality rate was 0.85/100,000. Among 46 fatal cases, 58.7% were male and median age was 7 years. Underlying diseases were present in 47.8%; neurologic diseases (63.6%) and malignancy (13.6%) most common. Only four had history of COVID-19 immunization. COVID-19 associated deaths occurred at median 2 days from diagnosis (range: -1 to 21). Among COVID-19 deaths, 41.3% occurred before admission; 2 before hospital arrival and 17 in the emergency department. Among children whose cause was documented, myocarditis, respiratory and multiorgan failure were most common. COVID-19 associated death was seen early after diagnosis in children and public health policies to provide access to medical care for children with COVID-19 are essential during the pandemic.

Threshold of Quantitative Cytomegalovirus DNA PCR for Preemptive Treatment in Pediatric Hematopoietic Stem Cell Transplant Recipients.

BACKGROUND: Consensus cytomegalovirus (CMV) DNA viral load thresholds for intervention in hematopoietic stem cell transplant (HSCT) recipients have not been established, especially in children. This study aimed at obtaining viral load thresholds of CMV DNA to guide preemptive management in pediatric HSCT recipients. MATERIALS AND METHODS: A total of 465 blood samples from 177 children who received HSCT between 2015 and 2019 were included in a single center in Korea. The samples were analyzed for CMV infection by both antigenemia assay and quantitative DNA polymerase chain reaction. The 2 assay results were compared for the 233 samples which were collected when antiviral treatment has not been initiated. We determined the viral loads corresponding to the antigenemia of 5 pp65-positive cells/2×10 5 white blood cells (WBCs) as the level for initiating preemptive therapy. RESULTS: Sixty percent of the samples were collected within 100 days (39.7% in 0 to 50 d, 60.2% in 0 to 100 d) from the graft infusion. The correlation between CMV DNA viral load and CMV antigenemia level increased significantly after 50 days from the graft infusion ( r =0.71 vs. r =0.93, P <0.0001). The correlation was greater in the antiviral treatment-naive group than the treatment group ( r =0.75 vs. r =0.66, P <0.0001). Under receiver operating characteristic curve analysis of the treatment-naive group, the estimated threshold CMV DNA viral loads corresponding to 5 pp65-positive cells/2×10 5 WBCs was 898 IU/mL. CONCLUSIONS: The CMV DNA levels that corresponded to 5 pp65-positive cells/2×10 5 WBCs was 900 IU/mL in the HSCT group. The proposed viral load thresholds can be used to guide preemptive therapy in pediatric HSCT recipients, especially in the preengraftment period.

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.

Preliminary Guidelines for the Clinical Evaluation and Management of Long COVID.

Long-lasting coronavirus disease 2019 (COVID-19) symptoms beyond 12 weeks, the so-called 'long COVID' have been increasingly reported worldwide. Long COVID can be manifested in various forms, and there is an increasing demand for proper assessment and management. However, it is challenging when trying to determine the best-practice standards of care based on the current evidence because there is no internationally agreed clinical definition or clear treatment pathway. Therefore, the present guidelines have been drafted to provide advice on diagnosis and management based on the latest updated available evidence and the consensus of expert opinion. So far, no standard test and drug treatment can be strongly recommended for patients with long COVID because of a lack of evidence. The present guidelines provide advice based on 12 key questions, including appropriate interventions for long COVID that can be used in clinical practice. Continuous careful observation and studies related to long COVID are needed for the long-term impact of COVID-19 and proper management for long COVID to be determined.

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.

Clinical Characteristics and Prognosis of the Modified Probable Pneumocystis jirovecii Pneumonia in Korean Children, 2001-2021.

There are few data about Pneumocystis jirovecii pneumonia (PCP) in children, particularly in developed countries. This study investigated the clinical characteristics and prognosis of the clinical PCP in non-HIV-infected Korean children. Children with positive results for the staining and/or polymerase chain reaction (PCR) for P. jirovecii between 2001 and 2021 were identified. Patients were grouped into clinical PCP, which comprised proven and modified probable cases, and non-PCP groups. Modified probable PCP (mp-PCP) indicate the case which P. jirovecii was detected by conventional PCR rather than real-time PCR test. The differences in demographic and clinical characteristics were analyzed between the groups. A total of 110 pneumonia cases with positive results for P. jirovecii PCR and/or stain were identified from 107 children. Of these, 28.2% were classified as non-PCP, 12.7% of proven PCP, and 59.1% of mp-PCP. Compared with the non-PCP group, the mp-PCP group had a significantly higher rate of solid organ transplantation (3.2% vs. 24.6%), fever (58.1% vs. 76.9%), tachypnea (25.8% vs. 66.2%), dyspnea (48.4% vs. 83.1%), desaturation (48.4% vs. 80.0%), and bilateral ground-glass opacity on chest radiograph (19.4% vs. 73.8%). However, when the mp-PCP group was compared with the proven PCP group, there was no statistically significant difference. For children with clinical PCP, age under 5 years of age (odds ratio [OR] 10.7), hospital-onset (OR 6.9), and desaturation as initial symptom (OR 63.5) were significant risk factors for death in multivariable analysis. Modified probable PCP might reliably reflect true PCP in terms of patient's demographic, clinical features, treatment response, and prognosis. Immunocompromised children with hospital-onset pneumonia who are younger than 5 years of age and have desaturation would be more cautiously and aggressively managed for survival through the screening for P. jirovecii by conventional PCR on appropriate lower respiratory specimens.

SARS-CoV-2 shedding dynamics and transmission in immunosuppressed patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern have been emerging. However, knowledge of temporal and spatial dynamics of SARS-CoV-2 is limited. This study characterized SARS-CoV-2 evolution in immunosuppressed patients with long-term SARS-CoV-2 shedding for 73-250 days, without specific treatment. We conducted whole-genome sequencing of 27 serial samples, including 26 serial samples collected from various anatomic sites of two patients and the first positive sample from patient 2's mother. We analysed the intrahost temporal dynamics and genomic diversity of the viral population within different sample types. Intrahost variants emerging during infection showed diversity between individual hosts. Remarkably, N501Y, P681R, and E484K, key substitutions within spike protein, emerged in vivo during infection and became the dominant population. P681R, which had not yet been detected in the publicly available genome in Korea, appeared within patient 1 during infection. Mutually exclusive substitutions at residues R346 (R346S and R346I) and E484 (E484K and E484A) of spike protein and continuous turnover of these substitutions occurred. Unique genetic changes were observed in urine samples. A household transmission from patient 2 to his mother, at least 38 days after the diagnosis, was characterized. Viruses may differently mutate and adjust to the host selective pressure, which could enable the virus to replicate efficiently for fitness in each host. Intrahost variants could be candidate variants likely to spread to the population eventually. Our findings may provide new insights into the dynamics of SARS-CoV-2 in response to interactions between the virus and host.