Effectiveness of Bivalent mRNA Booster Vaccine Against COVID-19 in Korea.

BACKGROUND: Bivalent booster mRNA vaccines containing the omicron-variant strains have been introduced worldwide in the autumn of 2022. Nevertheless, the omicron subvariants evoked another large coronavirus disease 2019 (COVID-19) pandemic wave in late 2022 and early 2023. METHODS: A retrospective, test-negative, case-control study was conducted to estimate the vaccine effectiveness (VE) of bivalent COVID-19 vaccines in 8 university hospitals between January and February 2023. The case and control groups were divided based on nasopharyngeal COVID-19 real-time polymerase chain reaction results and matched based on age, sex, hospital, and date (week) of the test performed. The VE of the BA.1- or BA.4/BA.5-based mRNA vaccines were estimated. VE was calculated using the 1-adjusted odds ratio from multivariable logistic regression. RESULTS: In total, 949 patients and 947 controls were enrolled in this study. VE for the BA.4/BA.5-based bivalent mRNA vaccine was 43% (95% confidence interval [CI], 17, 61%). In subgroup analysis based on age and underlying medical conditions, BA.4/BA.5-based bivalent mRNA vaccine was effective against old adults aged ≥ 65-years (VE, 55%; 95% CI, 23, 73%) and individuals with comorbidities (VE, 54%; 95% CI, 23, 73%). In comparison, the BA.1-based bivalent mRNA vaccine did not demonstrate statistically significant effectiveness (VE, 25%; 95% CI, -8, 49%). CONCLUSION: The BA.4/BA.5-based bivalent mRNA booster vaccine provided significant protection against COVID-19 in the Korean adults, especially in the older adults aged ≥ 65 years and in individuals with underlying medical conditions.

Impact of Infection Prevention Programs on Catheter-Associated Urinary Tract Infections Analyzed in Multicenter Study.

BACKGROUND: Catheter-associated urinary tract infections (CAUTIs) account for a large proportion of healthcare-associated infections and have a significant impact on morbidity, length of hospital stay, and mortality. Adherence to the recommended infection prevention practices can effectively reduce the incidence of CAUTIs. This study aimed to assess the characteristics of CAUTIs and the efficacy of prevention programs across hospitals of various sizes. METHODS: Intervention programs, including training, surveillance, and monitoring, were implemented. Data on the microorganisms responsible for CAUTIs, urinary catheter utilization ratio, rate of CAUTIs per 1,000 device days, and factors associated with the use of indwelling catheters were collected from 2017 to 2019. The incidence of CAUTIs and associated data were compared between university hospitals and small- and medium-sized hospitals. RESULTS: Thirty-two hospitals participated in the study, including 21 university hospitals and 11 small- and medium-sized hospitals. The microorganisms responsible for CAUTIs and their resistance rates did not differ between the two groups. In the first quarter of 2018, the incidence rate was 2.05 infections/1,000 device-days in university hospitals and 1.44 infections/1,000 device-days in small- and medium-sized hospitals. After implementing interventions, the rate gradually decreased in the first quarter of 2019, with 1.18 infections/1,000 device-days in university hospitals and 0.79 infections/1,000 device-days in small- and medium-sized hospitals. However, by the end of the study, the infection rate increased to 1.74 infections/1,000 device-days in university hospitals and 1.80 infections/1,000 device-days in small- and medium-sized hospitals. CONCLUSION: We implemented interventions to prevent CAUTIs and evaluated their outcomes. The incidence of these infections decreased in the initial phases of the intervention when adequate support and personnel were present. The rate of these infections may be reduced by implementing active interventions such as consistent monitoring and adherence to guidelines for preventing infections.

Interim Estimates of 2023-2024 Seasonal Influenza Vaccine Effectiveness Among Adults in Korea.

In the 2023-2024 season, the influenza epidemic in South Korea peaked earlier than in recent years. In this study, we aimed to estimate the interim vaccine effectiveness (VE) of the influenza vaccination to prevent influenza during the early season. From November 1, 2023, to December 31, 2023, we enrolled 2,632 subjects with influenza-like illness from eight hospitals participating in hospital-based influenza morbidity and mortality surveillance. A retrospective test-negative case-control study was conducted to estimate the VE. The results showed an adjusted VE of 22.5% (95% confidence interval [CI], 6.6 to 35.8) for the total population. The adjusted VE was 22.3% (95% CI, 6.1 to 35.7) for influenza A and 9.4% (95% CI, -51.3 to 45.7) for influenza A/H1N1. Full results of the analysis will be reported.

Clinical Characteristics and Risk Factors for Mortality in Critical COVID-19 Patients Aged 50 Years or Younger During Omicron Wave in Korea: Comparison With Patients Older Than 50 Years of Age.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has caused the death of thousands of patients worldwide. Although age is known to be a risk factor for morbidity and mortality in COVID-19 patients, critical illness or death is occurring even in the younger age group as the epidemic spreads. In early 2022, omicron became the dominant variant of the COVID-19 virus in South Korea, and the epidemic proceeded on a large scale. Accordingly, this study aimed to determine whether young adults (aged ≤ 50 years) with critical COVID-19 infection during the omicron period had different characteristics from older patients and to determine the risk factors for mortality in this specific age group. METHODS: We evaluated 213 critical adult patients (high flow nasal cannula or higher respiratory support) hospitalized for polymerase chain reaction-confirmed COVID-19 in nine hospitals in South Korea between February 1, 2022 and April 30, 2022. Demographic characteristics, including body mass index (BMI) and vaccination status; underlying diseases; clinical features and laboratory findings; clinical course; treatment received; and outcomes were collected from electronic medical records (EMRs) and analyzed according to age and mortality. RESULTS: Overall, 71 critically ill patients aged ≤ 50 years were enrolled, and 142 critically ill patients aged over 50 years were selected through 1:2 matching based on the date of diagnosis. The most frequent underlying diseases among those aged ≤ 50 years were diabetes and hypertension, and all 14 patients who died had either a BMI ≥ 25 kg/m² or an underlying disease. The total case fatality rate among severe patients (S-CFR) was 31.0%, and the S-CFR differed according to age and was higher than that during the delta period. The S-CFR was 19.7% for those aged ≤ 50 years, 36.6% for those aged > 50 years, and 38.1% for those aged ≥ 65 years. In multivariate analysis, age (odds ratio [OR], 1.084; 95% confidence interval [CI], 1.043-1.127), initial low-density lipoprotein > 600 IU/L (OR, 4.782; 95% CI, 1.584-14.434), initial C-reactive protein > 8 mg/dL (OR, 2.940; 95% CI, 1.042-8.293), highest aspartate aminotransferase > 200 IU/L (OR, 12.931; 95% CI, 1.691-98.908), and mechanical ventilation implementation (OR, 3.671; 95% CI, 1.294-10.420) were significant independent predictors of mortality in critical COVID-19 patients during the omicron wave. A similar pattern was shown when analyzing the data by age group, but most had no statistical significance owing to the small number of deaths in the young critical group. Although the vaccination completion rate of all the patients (31.0%) was higher than that in the delta wave period (13.6%), it was still lower than that of the general population. Further, only 15 (21.1%) critically ill patients aged ≤ 50 years were fully vaccinated. Overall, the severity of hospitalized critical patients was significantly higher than that in the delta period, indicating that it was difficult to find common risk factors in the two periods only with a simple comparison. CONCLUSION: Overall, the S-CFR of critically ill COVID-19 patients in the omicron period was higher than that in the delta period, especially in those aged ≤ 50 years. All of the patients who died had an underlying disease or obesity. In the same population, the vaccination rate was very low compared to that in the delta wave, indicating that non-vaccination significantly affected the progression to critical illness. Notably, there was a lack of prescription for Paxlovid for these patients although they satisfied the prescription criteria. Early diagnosis and active initial treatment was necessary, along with the proven methods of vaccination and personal hygiene. Further studies are needed to determine how each variant affects critically ill patients.

Effects of Non-Pharmacological Interventions on Respiratory Viruses Other Than SARS-CoV-2: Analysis of Laboratory Surveillance and Literature Review From 2018 to 2021.

BACKGROUND: Since the global coronavirus disease 2019 (COVID-19) pandemic, non-pharmacological interventions (NPIs) such as extensive and comprehensive hand hygiene, mask-wearing, and social distancing have been implemented globally. This study aimed to investigate changes in respiratory viruses other than severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that occurred following the implementation of these NPIs. METHODS: From January 2018 to December 2021, influenza-like illness patient specimens and specimens from the Korea Influenza and Respiratory Viruses Surveillance System were analyzed at the Incheon Metropolitan City Institute of Public Health and Environment. Oropharyngeal or nasopharyngeal swab samples from respiratory infection patients were transferred in a virus transport medium at 4°C. After RNA or DNA extraction, respiratory virus-specific genes for human influenza virus (IFV), adenovirus (ADV), parainfluenza virus (PIV), respiratory syncytial virus (RSV), human rhinovirus (hRV), human coronavirus, human bocavirus, and human metapneumovirus were detected by individual real-time reverse transcription polymerase chain reaction. RESULTS: A total 3,334 samples were collected. After NPI was implemented, the detection of respiratory viruses other than SARS-CoV-2 decreased overall. The yearly detection rate of respiratory viruses was decreased from 69.5% (399/574) in 2018 and 73.3% (505/689) in 2019 to 19.8% (206/1,043) in 2020 and 34.9% (365/1,028) in 2021. The epidemic was more prominent in respiratory viruses such as IFV and RSV, which were considered dominant viruses, especially those with viral envelopes. Among viruses that were not considered dominant, hRV showed no clear change before and after NPI, while PIV showed a rapid increase compared to the existing dominant viruses between October-December 2021, after the increase in the number of gatherings started at the end of September and the "Relaxing COVID19 and mitigation policy," which was implemented on November 1. CONCLUSION: NPI seems to have influenced the isolation and transmission of respiratory viruses in South Korea. In the future, additional studies focusing on the isolation and transmission patterns of respiratory viruses following NPI are needed.

Clinical Characteristics and Risk Factors for Mortality in Critical Coronavirus Disease 2019 Patients 50 Years of Age or Younger During the Delta Wave: Comparison With Patients > 50 Years in Korea.

BACKGROUND: Numerous patients around the globe are dying from coronavirus disease 2019 (COVID-19). While age is a known risk factor, risk analysis in the young generation is lacking. The present study aimed to evaluate the clinical features and mortality risk factors in younger patients (≤ 50 years) with a critical case of COVID-19 in comparison with those among older patients (> 50 years) in Korea. METHODS: We analyzed the data of adult patients only in critical condition (requiring high flow nasal cannula oxygen therapy or higher respiratory support) hospitalized with PCR-confirmed COVID-19 at 11 hospitals in Korea from July 1, 2021 to November 30, 2021 when the delta variant was a dominant strain. Patients' electronic medical records were reviewed to identify clinical characteristics. RESULTS: During the study period, 448 patients were enrolled. One hundred and forty-two were aged 50 years or younger (the younger group), while 306 were above 50 years of age (the older group). The most common pre-existing conditions in the younger group were diabetes mellitus and hypertension, and 69.7% of the patients had a body mass index (BMI) > 25 kg/m². Of 142 younger patients, 31 of 142 patients (21.8%, 19 women) did not have these pre-existing conditions. The overall case fatality rate among severity cases was 21.0%, and it differed according to age: 5.6% (n = 8/142) in the younger group, 28.1% in the older group, and 38% in the ≥ 65 years group. Age (odds ratio [OR], 7.902; 95% confidence interval [CI], 2.754-18.181), mechanical ventilation therapy (OR, 17.233; 95% CI, 8.439-35.192), highest creatinine > 1.5 mg/dL (OR, 17.631; 95% CI, 8.321-37.357), and combined blood stream infection (OR, 7.092; 95% CI, 1.061-18.181) were identified as independent predictors of mortality in total patients. Similar patterns were observed in age-specific analyses, but most results were statistically insignificant in multivariate analysis due to the low number of deaths in the younger group. The full vaccination rate was very low among study population (13.6%), and only three patients were fully vaccinated, with none of the patients who died having been fully vaccinated in the younger group. Seven of eight patients who died had a pre-existing condition or were obese (BMI > 25 kg/m²), and the one remaining patient died from a secondary infection. CONCLUSION: About 22% of the patients in the young critical group did not have an underlying disease or obesity, but the rate of obesity (BMI > 25 kg/m²) was high, with a fatality rate of 5.6%. The full vaccination rate was extremely low compared to the general population of the same age group, showing that non-vaccination has a grave impact on the progression of COVID-19 to a critical condition. The findings of this study highlight the need for measures to prevent critical progression of COVID-19, such as vaccinations and targeting young adults especially having risk factors.

Clinical and Virologic Effectiveness of Remdesivir Treatment for Severe Coronavirus Disease 2019 (COVID-19) in Korea: a Nationwide Multicenter Retrospective Cohort Study.

BACKGROUND: Remdesivir is widely used for the treatment of coronavirus disease 2019 (COVID-19), but controversies regarding its efficacy still remain. METHODS: A retrospective cohort study was conducted to evaluate the effect of remdesivir on clinical and virologic outcomes of severe COVID-19 patients from June to July 2020. Primary clinical endpoints included clinical recovery, additional mechanical ventilator (MV) support, and duration of oxygen or MV support. Viral load reduction by hospital day (HD) 15 was evaluated by calculating changes in cycle threshold (Ct) values. RESULTS: A total of 86 severe COVID-19 patients were evaluated including 48 remdesivir-treated patients. Baseline characteristics were not significantly different between the two groups. Remdesivir was administered an average of 7.42 days from symptom onset. The proportions of clinical recovery of the remdesivir and supportive care group at HD 14 (56.3% and 39.5%) and HD 28 (87.5% and 78.9%) were not statistically different. The proportion of patients requiring MV support by HD 28 was significantly lower in the remdesivir group than in the supportive care group (22.9% vs. 44.7%, P = 0.032), and MV duration was significantly shorter in the remdesivir group (average, 1.97 vs. 5.37 days; P = 0.017). Analysis of upper respiratory tract specimens demonstrated that increases of Ct value from HD 1-5 to 11-15 were significantly greater in the remdesivir group than the supportive care group (average, 10.19 vs. 5.36; P = 0.007), and the slope of the Ct value increase was also significantly steeper in the remdesivir group (average, 5.10 vs. 2.68; P = 0.007). CONCLUSION: The remdesivir group showed clinical and virologic benefit in terms of MV requirement and viral load reduction, supporting remdesivir treatment for severe COVID-19.

Positivity of Carbapenemase-producing Enterobacteriaceae in Patients Following Exposure within Long-term Care Facilities in Seoul, Korea.

BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) are emerging as a worldwide threat. Long-term care facilities (LTCFs) are considered a reservoir for CPE and play a central role in transmission to acute care hospitals. We investigated the CPE positivity in patients exposed to CPE in LTCFs. Furthermore, we analyzed the CPE positivity rates in the environment exposed to CPE. METHODS: We collected rectal swab specimens from patients residing in LTCFs who were exposed to CPE. Environmental sampling was performed by infection control practitioners from sites classified as patient private space, common space in the patient room, common space other than patient rooms, and nursing station. Each sample was cultured on a Chrom Klebsiella pneumoniae carbapenemase (KPC) agar for CPE screening. The positive isolates were subjected to a polymerase chain reaction to identify the presence of blaKPC, blaVIM, blaIMP, blaOXA-48, and blaNDM and determine CPE genotype. RESULTS: From 65 index cases, a total of 24 hospitals and 481 patients were enrolled; 414 patients who had resided in the same patient room as a patient with confirmed CPE and 67 patients who were newly admitted to that patient room. A total of 117 (24.3%) patients were positive for CPE among which 93 (22.5%, 93/414) were already admitted patients and 24 (35.8%, 24/67) were newly admitted patients. A total of 163 CPEs were detected and K. pneumoniae (n = 104, 63.8%) was the most common bacteria followed by Escherichia coli (n = 43, 26.4%) and Citrobacter koseri (n = 11, 6.7%). Environmental sampling was performed in 24 hospitals and 604 sites. A total of 12 sites (2.0%) were positive for CPE and sink in the nursing station (n = 6, 4.2%) was the most contaminated space. CONCLUSION: CPE colonization rates in patients exposed to CPE in LTCFs were higher than those found in acute care hospitals. Proper infection control measures for detecting and reducing CPE colonization in patients residing in LTCFs are required. Newly admitted patients could also be carriers; therefore, infection control for newly admitted patients also needs to be thorough.

Safety and Effectiveness of Peramivir in Korean Adult Influenza Patients: Prospective Observational Study Based on Post-Marketing Surveillance Data.

BACKGROUND: The safety and clinical effectiveness data of peramivir in the real clinical field are limited. A prospective observational study was conducted based on the post-marketing surveillance data to evaluate the post-marketing safety and effectiveness of peramivir in Korean adults with seasonal influenza. METHODS: Among adults aged 20 years or older who were diagnosed with influenza A or B, patients who started peramivir within 48 hours from the initial symptoms of influenza were enrolled. All adverse events (AEs) that occurred within 7 days after administration of peramivir were checked. For the evaluation of effectiveness, changes in the severity of influenza symptoms and daily living performance were examined before and 7 days after the administration of peramivir. The date on which influenza related symptoms disappeared was checked. RESULTS: A total of 3,024 patients were enrolled for safety evaluation and 2,939 patients were for effectiveness evaluation. In the safety evaluation, 42 AEs were observed in 35 (1.16%) patients. The most common AE was fever. AEs were mostly rated as mild in severity. Serious AEs were observed in 10 patients and two of them died. However, both deaths were considered to be less relevant to peramivir. In the effectiveness evaluation, the severity of influenza symptoms decreased by 10.68 ± 4.01 points and daily living performance was improved 5.59 ± 2.16 points. Influenza related symptoms disappeared on average 3.02 ± 2.39 days after peramivir administration. CONCLUSION: Peramivir showed a tolerable safety profile and acceptable effectiveness in Korean adult patients with seasonal influenza.

Immunogenicity and Safety of a Live Attenuated Zoster Vaccine (ZOSTAVAX™) in Korean Adults.

A live attenuated zoster vaccine (ZOSTAVAX™, Merck & Co., Inc.) was approved by the Korea Ministry of Food and Drug Safety in 2009. However, the immunogenicity and safety of the vaccine has not been assessed in Korean population. This is multi-center, open-label, single-arm study performed with 180 healthy Korean adults ≥ 50 yr of age. The geometric mean titer (GMT) and geometric mean fold rise (GMFR) of varicella zoster virus (VZV) antibodies were measured by glycoprotein enzyme-linked immunosorbent assay (gpELISA) at 4 weeks post-vaccination. Subjects were followed for exposure to varicella or herpes zoster (HZ), the development of any varicella/varicella-like or HZ/HZ-like rashes, and any other clinical adverse experiences (AEs) for 42 days post-vaccination. For the 166 subjects included in the per-protocol population, the GMT at Day 1 was 66.9. At 4 weeks post-vaccination, the GMT for this population was 185.4, with a GMFR of 2.8 (95% CI, 2.5-3.1). Of the 180 subjects vaccinated, 62.8% experienced ≥ 1 AE, with 53.3% of subjects reporting injection-site AEs. The most frequently reported injection-site AEs were erythema (45.0%) with the majority being mild in intensity. Overall, 44 (24.4%) subjects experienced ≥ 1 systemic AE, 10 (5.5%) subjects experienced a systemic vaccine-related AE, and 3 (1.7%) subjects experienced ≥ 1 serious AE not related to vaccine. No subjects reported a VZV-like rash. There was no subject of death and no subject discontinued due to an adverse event. A single dose of zoster vaccine induced VZV-specific gpELISA antibody response and was generally well-tolerated in healthy Korean adults ≥50 yr of age (registry at www.clinicaltrial.gov No. NCT01556451).

Immunity and the burden of herpes zoster.

The burden of herpes zoster may be related to patients' immunity, although this has not been studied extensively. This hypothesis was tested in a matched case-control study of patients with herpes zoster who sought treatment at one of seven university hospitals in Korea from January 1, 2007, to December 31, 2010. Patients diagnosed with herpes zoster were placed into three groups based on their immune status: severely immunocompromised, mild-to-moderately immunocompromised, and normal immunity. Each patient in the severely immunocompromised group was matched with one patient in the mild-to-moderately immunocompromised group and one patient in the normal immunity group in the same hospital based on age, sex, and date of herpes zoster onset. A total of 582 patients with herpes zoster were included in the analysis: 194 in each of the three groups. Patients in the severely immunocompromised group had the highest herpes zoster-related hospitalization rate as compared to patients in the mild-to-moderately immunocompromised and normal immune groups (P < 0.01). The length of hospital stay and herpes zoster-related medical cost increased significantly with the deterioration of patients' immunity (P < 0.01, respectively). Cutaneous complications occurred more frequently in the severely immunocompromised group than in the other two groups (P < 0.01). An increase in herpes zoster burden was observed as the patients' immunity decreased. Therefore, effective measures are necessary to prevent herpes zoster and reduce its burden in severely immunocompromised patients.

Effectiveness of COVID-19 XBB.1.5 monovalent mRNA vaccine in Korea: interim analysis.

As coronavirus disease-2019 (COVID-19) becomes an endemic disease, the virus continues to evolve and become immunologically distinct from previous strains. Immune imprinting has raised concerns about bivalent mRNA vaccines containing both ancestral virus and Omicron variant. To increase efficacy against the predominant strains as of the second half of 2023, the updated vaccine formulation contained only the mRNA of XBB.1.5 sublineage. We conducted a multicenter, test-negative, case-control study to estimate XBB.1.5 monovalent vaccine effectiveness (VE) and present the results of an interim analysis with data collected in November 2023. Patients who underwent COVID-19 testing at eight university hospitals were included and matched based on age (19-49, 50-64, and ≥65 years) and sex in a 1:1 ratio. VE was calculated using the adjusted odds ratio derived from multivariable logistic regression. Of the 992 patients included, 49 (5.3%) received the XBB.1.5 monovalent vaccine at least 7 days before COVID-19 testing. Patients with COVID-19 (cases) were less likely to have received the XBB.1.5 monovalent vaccine (case 3.5% vs. control 7.2%, p=0.019) and to have a history of COVID-19 within 6 months (2.2% vs. 4.6%, p=0.068). In contrast, patients with COVID-19 were more likely to be healthcare workers (8.2% vs. 3.0%, p=0.001) and to have chronic neurological diseases (16.7% vs. 11.9%, p=0.048). The adjusted VE of the XBB.1.5 monovalent mRNA vaccine was 56.8% (95% confidence interval: 18.7-77.9%). XBB.1.5 monovalent mRNA vaccine provided significant protection against COVID-19 in the first one to two months after vaccination.

CT differentiation of abscess and non-infected fluid in the postoperative neck.

BACKGROUND: Differentiation of postoperative neck abscess from non-infected fluid is important because the treatment is different. PURPOSE: To determine specific CT findings that might help to differentiate abscesses from non-infected fluid collections in the postoperative neck. MATERIAL AND METHODS: We retrospectively reviewed CT scans of 50 patients (43 men and 7 women; mean age, 62.5 ± 8.9 years) who had postoperative fluid collections in the neck (26 abscesses and 24 non-infected fluid collections). Diagnosis of an abscess was determined by a positive bacteria culture from the fluid collection. Diagnoses were correlated with the following CT findings: anatomic spaces involved, the maximum transverse diameter, margin, attenuation, rim enhancement, gas bubbles, and manifestations of soft tissue adjacent to a fluid collection. RESULTS: Rim enhancement pattern and soft tissue manifestations showed significant differences between abscess and non-infected fluid. The reliable CT findings for abscess were: (i) rim enhancement > 50% of the circumference, 54% sensitive, 71% specific, and 62% accurate; and (ii) severe soft tissue manifestations, 39% sensitive, 92% specific, and 64% accurate. There were no significant differences in the anatomic spaces involved, the maximum transverse diameter, margin, attenuation, and gas bubbles between abscess and non-infected fluid. CONCLUSION: CT findings that may help differentiate postoperative neck abscess from non-infected fluid were rim enhancement > 50% of the circumference and severe soft tissue manifestations.

Wastewater Knows Pathogen Spread: Analysis of Residential Wastewater for Infectious Microorganisms including SARS-CoV-2.

BACKGROUND: We aimed to identify the genes of 35 pathogens, including viruses, bacteria, and protozoa that cause waterborne infectious diseases, and to assess the feasibility of a wastewater-based surveillance system. MATERIALS AND METHODS: Wastewater was aseptically sampled once a month from 2 sites. A total of 1 L of wastewater from each site underwent 0.2 µm filtration to generate the sample A. Subsequently, 200 ul of the filtered water was ultra-filtered and concentrated to generate the sample B, which was mixed with sample A in a 1:1 ratio. We performed a Filmarray® Gastrointestinal (GI) panel (BioFire Diagnnostics', Salt Lake City, UT, USA) test to simultaneously detect 13 enterobacteria, 5 enterovirus, and 4 protozoa. RNA was extracted to assess 18 types of viruses. RESULTS: Severe acute respiratory syndrome coronavirus 2 adenovirus, bocavirus, and rhinovirus was detected at both site. Norovirus GI/GII was continuously detected at both sites. Moreover, adenovirus, group A rotaviruses, and hepatitis A virus were frequently detected; however, hepatitis E virus was absent at either site. Campylobacter, enteroaggregative Escherichia coli, enterotoxigenic E. coli, Shiga toxin-producing E. coli, and Clostridioides difficile toxin A/B were detected at both sites. Giardia lamblia was also detected in both sites. CONCLUSION: We analyze multiple infectious disease pathogens under sample surveillance with incidence. Further in-depth studies on wastewater-based surveillance will be feasible and important.

Immunogenicity and safety of SARS-CoV-2 recombinant protein nanoparticle vaccine GBP510 adjuvanted with AS03: interim results of a randomised, active-controlled, observer-blinded, phase 3 trial.

Background: GBP510 vaccine contains self-assembling, recombinant nanoparticles displaying SARS-CoV-2 spike receptor-binding domains. We report interim phase 3 immunogenicity results for GBP510 adjuvanted with AS03 (GBP510/AS03) compared with ChAdOx1-S (Vaxzevria, AstraZeneca) in healthy adults aged ≥18 years, up to 6 months after the second dose. Methods: This was a randomised, active-controlled, observer-blinded, parallel group, phase 3 study, conducted at 38 sites across six countries (South Korea, Philippines, Thailand, Vietnam, Ukraine and New Zealand). Cohort 1 (no history of SARS-CoV-2 infection/COVID-19 vaccination) was randomised 2:1 to receive two doses of GBP510/AS03 or ChAdOx1-S (immunogenicity and safety), while Cohort 2 (regardless of baseline serostatus) was randomised 5:1 (safety). Primary objectives were to demonstrate superiority in geometric mean titre (GMT) and non-inferiority in seroconversion rate (SCR; ≥4-fold rise from baseline) of GBP510/AS03 vs. ChAdOx1-S for neutralising antibodies against the ancestral strain by live-virus neutralisation assay. Secondary objectives included assessment of safety and reactogenicity (long-term 6 months cut-off date: 09 August 2022). This study was registered on ClinicalTrials.gov (NCT05007951). Findings: Between 30 August 2021 and 11 January 2022, a total of 4913 participants were screened and 4036 participants (1956 in Cohort 1 and 2080 in Cohort 2) who met eligibility criteria were enrolled and randomised to receive 2 doses of GBP510/AS03 (n = 3039) or ChAdOx1-S (n = 997). Most participants were Southeast Asian (81.5%) and aged 18-64 years (94.7%). The primary objectives assessed in per-protocol set included 877 participants in GBP510/AS03 and 441 in ChAdOx1-S group: at 2 weeks after the second vaccination, the GMT ratio (GBP510/AS03/ChAdOx1-S) in per-protocol set was 2.93 (95% CI 2.63-3.27), demonstrating superiority (95% CI lower limit >1) of GBP510/AS03; the between-group SCR difference of 10.8% (95% CI 7.68-14.32) also satisfied the non-inferiority criterion (95% CI lower limit > -5%). Neutralizing antibody titres sustained higher for the GBP510/AS03 group compared to the ChAdOx1-S group through 6 months after the second vaccination. In Safety analysis (Cohort 1 & 2), the proportion of participants with adverse events (AEs) after any vaccination was higher with GBP510/AS03 vs. ChAdOx1-S for solicited local AEs (56.7% vs. 49.2%), but was similar for solicited systemic AEs (51.2% vs. 53.5%) and unsolicited AEs (13.3% vs. 14.6%) up to 28 days after the second vaccination. No safety concerns were identified during follow-up for 6 months after the second vaccination. Interpretation: Our interim findings suggested that GBP510/AS03 met the superiority criterion for neutralising antibodies and non-inferiority criterion for SCR compared with ChAdOx1-S, and showed a clinically acceptable safety profile. Funding: This work was supported, in whole or in part, by funding from CEPI and the Bill & Melinda Gates Foundation Investments INV-010680 and INV-006462. The Bill & Melinda Gates Foundation supported this project for the generation of IND-enabling data and CEPI supported this clinical study.

Red blood cell transfusions are associated with lower mortality in patients with severe sepsis and septic shock: a propensity-matched analysis*.

OBJECTIVES: To evaluate the effects of transfusions in patients with severe sepsis and septic shock on mortality. DESIGN: Propensity-matched analysis of a prospective observational database (April 2005 to February 2009). SETTING: Twenty-two medical and surgical intensive care units in 12 teaching hospitals in Korea. PATIENTS: One thousand fifty-four patients with community-acquired severe sepsis and septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 1,054 patients, 407 (38.6%) received a blood transfusion. The mean pretransfusion hemoglobin level was 7.7 ± 1.2 g/dL. Transfused patients had higher 28-day and in-hospital mortality rates (32.7% vs. 17.3%; p < .001, 41.3% vs. 20.3%; p < .001, respectively) and a longer duration of hospital stay (21 [interquartile range, 10-35] vs. 13 [interquartile range, 8-24] days; p < .001), but were more severely ill at admission (lower systolic blood pressure, higher Acute Physiology and Chronic Health Evaluation II score, and Sequential Organ Failure Assessment score at admission). In 152 pairs matched according to the propensity score depending on patient transfusion status, transfused patients had a lower risk of 7-day (9.2% vs. 27.0%; p < .001), 28-day (24.3% vs. 38.8%; p = .007), and in-hospital mortality rates (31.6% vs. 42.8%; p = .044). After adjusting for blood transfusion as a time-dependent variable in multivariable analysis, blood transfusion was independently associated with lower risk of 7-day (hazard ratio 0.42, 95% confidence interval 0.19-0.50, p = .026), 28-day (hazard ratio 0.43, 95% confidence interval 0.29-0.62, p < .001), and in-hospital mortality (hazard ratio 0.51, 95% confidence interval 0.39-0.69, p < .001). CONCLUSIONS: In this observational study of patients with community-acquired severe sepsis and septic shock, red blood cell transfusions were associated with lower risk of mortality.

The clinical effectiveness of oseltamivir in mild cases of pandemic influenza A H1N1 2009 infection.

BACKGROUND: Oseltamivir is widely used for the treatment of influenza infection, but data on its effectiveness in treating infections with pandemic influenza A H1N1 2009 are scarce. Therefore, we compared the effectiveness of oseltamivir and routine symptomatic treatment in pandemic influenza A H1N1 2009 infection. METHODS: Between August and October 2009, among laboratory confirmed influenza cases who were aged over 15 y with no underlying disease, 90 patients with oseltamivir treatment and 72 patients with symptomatic treatment were evaluated by telephone interviews to compare clinical outcomes. No patient was hospitalized. The primary end-point was the duration of illness. We also assessed the time to attain a sense of well-being and the time to return to normal activity. RESULTS: There was no statistically significant difference in the duration of illness between the oseltamivir-treated group and the symptomatic treatment group (mean duration after the start of treatment, 6.50 ± 3.75 days vs 7.04 ± 3.75 days). There was also no statistically significant difference between the 2 groups in the time to a sense of well-being (1.70 ± 1.57 days vs 2.00 ± 2.12 days) and to return to normal activity (7.13 ± 2.61 days vs 7.58 ± 2.71 days). The complication rate was very low (only 2 cases of mild pneumonia in oseltamivir recipients) and no significant difference was found between the 2 groups (p = 0.50). CONCLUSIONS: Oral oseltamivir treatment does not significantly reduce the duration of illness or influenza-related complications in mild pandemic influenza A H1N1 2009 virus infection in previously healthy adults.

Prescription of antibiotics for adults hospitalized with community-acquired pneumonia in Korea in 2004: a population-based descriptive study.

BACKGROUND AND OBJECTIVE: Community-acquired pneumonia (CAP) is generally considered to be a major cause of morbidity and mortality. There is much controversy regarding the optimal choice of antibiotics for patients with CAP. The aim of this study was to identify the antibiotics prescribed for adults hospitalized with CAP in Korea during a calendar year. METHODS: This population-based, descriptive epidemiological study was performed using data from nationwide health insurance claims from 1 January 2004 to 31 December 2004. The study population was adults (≥18 years old), who had been hospitalized with CAP as determined by discharge diagnosis, and who had been treated with antibiotics for ≥3 days. The exclusion criteria were tuberculosis, underlying malignancies and potential nosocomial pneumonia, based on the department providing care, or surgery reports during the admission. RESULTS: Of the 5592 adults hospitalized with CAP, data for 3662 (65.5%) patients was eligible for inclusion in the analysis. This included data for 1899 (51.9%) males, and 2045 (55.8%) patients ≥65 years of age. The most frequently prescribed antimicrobial regimen was ß-lactam/ß-lactamase inhibitors and fluoroquinolones in combination (31.0%), followed by ß-lactam/ß-lactamase inhibitors plus macrolides (30.2%), monotherapy (17.0%), ß-lactam/ß-lactamase inhibitors plus aminoglycosides (12.9%), ß-lactam/ß-lactamase inhibitors plus clindamycin (4.9%), and cephalosporins plus fluoroquinolones (2.5%). Monotherapy included, in decreasing order of use, cephalosporins (6.0%), fluoroquinolones (3.5%), ß-lactam/ß-lactamase inhibitors (2.3%) and macrolides (2.2%). CONCLUSIONS: In this study, patterns of antimicrobial prescription for patients hospitalized with CAP were assessed for the first time in Korea. There was divergence from the 2009 Korean guidelines for the treatment of CAP, reinforcing the need for assessment of physicians' adherence to the guidelines.

Epidemiological and clinical characteristics of community-acquired severe sepsis and septic shock: a prospective observational study in 12 university hospitals in Korea.

A prospective multicenter observational study was performed to investigate the epidemiology and outcomes of community-acquired severe sepsis and septic shock. Subjects included 1,192 adult patients admitted to the 22 participating intensive care units (ICUs) of 12 university hospitals in the Korean Sepsis Registry System from April, 2005 through February, 2009. Male accounted for 656 (55%) patients. Mean age was 65.0 ± 14.2 yr. Septic shock developed in 740 (62.1%) patients. Bacteremia was present in 422 (35.4%) patients. The 28-day and in-hospital mortality rates were 23.0% and 28.0%, respectively. Men were more likely to have comorbid illnesses and acute organ dysfunctions, and had higher mortality and clinical severity compared to women. While respiratory sources of sepsis were common in men, urinary sources were predominant in women. In the multivariate logistic regression analysis, cancer (odds ratio 1.89; 95% confidence interval 1.13-3.17), urinary tract infection (0.25; 0.13-0.46), APACHE II score (1.05; 1.02-1.09), SOFA score on day 1 (1.13; 1.06-1.21) and metabolic dysfunction (2.24, 1.45-3.45) were independent clinical factors for gender-related in-hospital mortality. This study provided epidemiological and clinical characteristics of community-acquired severe sepsis and septic shock in ICUs in Korea, and demonstrated the impact of clinical factors on gender difference in mortality.

Clinical Characteristics and Pregnancy-Related Outcomes of Pregnant Women Hospitalized with COVID-19 During the Delta Wave: A Single-Center Observational Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) during pregnancy is associated with increased disease severity and an increased risk of perinatal complications. However, few studies of pregnant women with COVID-19 have been conducted in Korea. The purpose of this study was to describe the clinical course and pregnancy outcomes of pregnant women admitted to our hospital with COVID-19 according to the severity. MATERIALS AND METHODS: This retrospective cohort study included women aged 18 years of age or older who were hospitalized in the Gachon University Gil Medical Center with COVID-19 during pregnancy between July 1, 2021 and January 31, 2022. COVID-19 severity was classified according to the "Criteria for severity classification by symptoms of COVID-19" presented by the Korea Disease Control and Prevention Agency. Severe cases were defined as those who required oxygen treatment administered via a high-flow nasal cannula or invasive mechanical ventilation or should be applied extracorporeal membrane oxygenation (ECMO) or continuous renal replacement therapy. RESULTS: A total of 103 pregnant women were hospitalized with COVID-19 during the study period. Their mean age was 33 (± 4.14) years, and 4 (3.9%) had been vaccinated against COVID-19. At the time of diagnosis of COVID-19, 3 (2.9%), 33 (32.0%), and 67 (65.1%) patients were in the first, second, and third trimester, respectively. The most common symptoms were cough (99 patients, 96.1%) and fever (85 patients, 82.5%). There was 1 (1.0%) asymptomatic patient. Forty patients (38.8%) required supplemental oxygen and 19 patients (18.4%) had severe disease. Of the 19 severe cases, 7 were in the 2nd trimester and 12 were in the 3rd trimester. Forty-one (39.8%) patients delivered, including two twin deliveries. Of the 41 cases of delivery, 14 were premature, 4 out of 21 (19.0%) in mild, 4 out of 12 (25.0%) in moderate, and 6 out of 8 (75.0%) in severe. Severe disease was associated with an increased rate of preterm birth (P = 0.012). Four of the 43 neonates (9.1%) received oxygen treatment. CONCLUSION: Pregnant women with COVID-19 had a high rate of severe disease and a high preterm delivery rate, especially among those with severe disease.