Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Background: With a rapid decrease in tuberculosis (TB) incidence, the significance of latent tuberculosis infection (LTBI) has been underscored in South Korea. Although South Korea does not have a high proportion of immigrants compared to other countries, there is a growing argument that it should actively embrace immigrants as a solution to address issues of low birth rates and population aging. This study aimed to assess TB incidence among immigrants who participated a pilot LTBI screening program in South Korea. Methods: Records of immigrants participated in a pilot LTBI screening program in South Korea between 2018 and 2019 were linked with Korean National TB Surveillance System to determine TB development. Participants underwent interferon-gamma release assay (IGRA) and chest X-rays. Standardized incidence ratios (SIRs) stratified by age, country of origin’s TB burden was calculated with a reference group of general South Korean population. Results: Of a total of 9,517 participants, 14 TB cases were identified. Participants with positive IGRA results who did not initiate LTBI treatment showed TB incidence of 312.5 per 100,000 person-years, whereas those with negative results showed TB incidence of 34.4 per 100,000 person-years, resulting in an incidence rate ratio of 9.08 (95% confidence interval [CI], 2.50–32.99). SIR of TB among total participants including those with negative IGRA results was 2.60 (95% CI, 1.54–4.38; P < 0.001), whereas SIR among those with positive IGRA results was 5.86 (95% CI, 3.15–10.89; P < 0.001). In the calculation of SIR among participants with positive IGRA results, those aged under 35 from high TB-burden countries or intermediate TBburden countries showed a high SIR (18.08; 95% CI, 2.55–128.37; P = 0.004), and 11.30 (95% CI, 2.82–45.16; P < 0.001), respectively). Contrary to previous reports that suggest the majority of elderly population with a positive IGRA result were due to remote infection and had a lower TB risk compared to younger ages, SIR among those aged 65 or over from intermediate TB-burden countries was 6.15 (95% CI, 0.87–43.69; P = 0.069), which was comparable to that in younger participants aged between 35 and 49 (SIR, 4.87; 95% CI, 1.22–19.49; P = 0.025) or those aged between 50 and 64 (SIR, 4.62; 95% CI, 1.73–12.31; P = 0.002). Conclusion Young immigrants with positive IGRA results from countries with high or intermediate TB burden showed a relatively high TB risk compared to a general South Korea population. In addition, unexpected high TB risk was observed among elderly immigrants with positive IGRA results. In establishing future policies for LTBI in immigrants in South Korea, screenings should primarily focus on younger age group (who aged under 35).Additionally, further research is needed on the high TB risk observed in elderly immigrants.

Background: In 2017, Korea implemented nationwide latent tuberculosis infection (LTBI) project targeting healthcare workers (HCWs). We aimed to assess its performance using the cascade of care model. Methods: We included 45,503 employees of medical institutions with positive interferongamma release assay result who participated between March 2017 and December 2018. We described percentages of LTBI participants completing each step in the cascade of care.Poisson regression model was conducted to assess individual characteristics and factors associated with not-visiting clinics for further care, not-initiating LTBI treatment, and notcompleting treatment. Results: Proportions of visiting clinics and initiating and completing treatment in HCWs were 54.9%, 38.5%, and 32.0%, respectively. Despite of less likelihood of visiting clinics and initiating LTBI treatment, older age ≥ 65 years were more likely to complete treatment (adjusted relative risk [aRR], 0.80; 95% confidence interval [CI], 0.64–0.99), compared to young age < 35 years. Compared to nurses, doctors were less likely to visit clinic; however, were more likely to initiate treatment (aRR, 0.88; 95% CI, 0.81–0.96). Those who visited public health centers were associated with not-initiating treatment (aRR, 1.34; 95% CI, 1.29–1.40). When treated at private hospitals, 9-month isoniazid monotherapy was less likely to complete treatment, compared to 3-month isoniazid and rifampicin combination therapy (aRR, 1.33; 95% CI, 1.16–1.53). Conclusion Among employees of medical institutions with LTBI, only one third completed treatment. Age, occupation, treatment center, and initial regimen were significantly related to LTBI treatment performance indicators. Rifampicin-based short treatment regimens were effective under standard of care.

Background: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

In 2017, the Korean government launched an unprecedentedly large-scaled latent tuberculosis infection (LTBI) screening project which covered more than a million individuals in congregate settings. A total of 1,047,689 participants of source population (n = 2,336,157) underwent LTBI testing from 2017 to 2018. The overall LTBI test uptake rate during this project was 44.8%. Workers in daycare centers (83.5%) and kindergartens (78.9%) showed high participation rate. A total of 1,012,206 individuals with valid results of interferongamma release assay (IGRA) were selected to constitute the IGRA cohort. Most of the enrolled participants in the IGRA cohort were in their working age. Approximately, threequarters of total enrolled population were female. Investigating the LTBI prevalence, stages of LTBI care cascade, natural history of LTBI, efficacy of LTBI treatment and cost-effectiveness of LTBI screening are feasible within this IGRA cohort.

In 2017, the Korean government launched an unprecedentedly large-scaled latent tuberculosis infection (LTBI) screening project which covered more than a million individuals in congregate settings. A total of 1,047,689 participants of source population (n = 2,336,157) underwent LTBI testing from 2017 to 2018. The overall LTBI test uptake rate during this project was 44.8%. Workers in daycare centers (83.5%) and kindergartens (78.9%) showed high participation rate. A total of 1,012,206 individuals with valid results of interferongamma release assay (IGRA) were selected to constitute the IGRA cohort. Most of the enrolled participants in the IGRA cohort were in their working age. Approximately, threequarters of total enrolled population were female. Investigating the LTBI prevalence, stages of LTBI care cascade, natural history of LTBI, efficacy of LTBI treatment and cost-effectiveness of LTBI screening are feasible within this IGRA cohort.

Background: The coronavirus disease 2019 (COVID-19) pandemic caused disruptions to healthcare systems and endangered the control and prevention of tuberculosis (TB). We investigated the nationwide effects of COVID-19 on the national Public-Private Mix (PPM) TB control project in Korea, using monitoring indicators from the Korean PPM monitoring database. Methods: The Korean PPM monitoring database includes data from patients registered at PPM hospitals throughout the country. Data of six monitoring indicators for active TB cases updated between July 2019 and June 2020 were collected. The data of each cohort throughout the country and in Daegu-Gyeongbuk, Seoul Metropolitan Area, and Jeonnam-Jeonbuk were collated to provide nationwide data. The data were compared using the χ 2 test for trend to evaluate quarterly trends of each monitoring indicator at the national level and in the prespecified regions. Results: Test coverages of sputum smear (P = 0.622) and culture (P = 0.815), drug susceptibility test (P = 0.750), and adherence rate to initial standard treatment (P = 0.901) at the national level were not significantly different during the study period. The rate of loss to follow-up among TB cases at the national level was not significantly different (P = 0.088) however, the treatment success rate among the smear-positive drug-susceptible pulmonary TB cohort at the national level significantly decreased, from 90.6% to 84.1% (P < 0.001). Treatment success rate in the Seoul metropolitan area also significantly decreased during the study period, from 89.4% to 84.5% (P = 0.006). Conclusion Our study showed that initial TB management during the COVID-19 pandemic was properly administered under the PPM project in Korea. However, our study cannot confirm or conclude a decreased treatment success rate after the COVID-19 pandemic due to limited data.

Background: The national Public-Private Mix (PPM) tuberculosis (TB) control project provides for the comprehensive management of TB patients at private hospitals in South Korea. Surveillance and monitoring of TB under the PPM project are essential toward achieving TB elimination goals. Methods: TB is a nationally notifiable disease in South Korea and is monitored using the surveillance system. The Korea Centers for Disease Control and Prevention quarterly generates monitoring indicators for TB management, used to evaluate activities of the PPM hospitals by the central steering committee of the national PPM TB control project. Based on the notification date, TB patients at PPM hospitals were enrolled in each quarter, forming a cohort, and followed up for at least 12 months to identify treatment outcomes. This report analyzed the dataset of cohorts the first quarter of 2016 through the fourth quarter of 2017. Results: The coverage of sputum, smear, and culture tests among the pulmonary TB cases were 92.8% and 91.5%, respectively. The percentage of positive sputum smear and culture test results were 30.7% and 61.5%, respectively. The coverage of drug susceptibility tests among the culture-confirmed cases was 92.8%. The treatment success rate among the smear-positive drug-susceptible cases was 83.2%. The coverage of latent TB infection treatment among the childhood TB contacts was significantly higher than that among the adult contacts (85.6% vs. 56.0%, p=0.001). Conclusion This is the first official report to analyze monitoring indicators, describing the current status of the national PPM TB control project. To sustain its effect, strengthening the monitoring and evaluation systems is essential.

BACKGROUND: The increasing rate of drug-resistant tuberculosis (TB) is a threat to the public health and TB control. In Korea, about 75~80% of TB patients are treated in private hospitals and the rate has been continuously increasing since 2000. METHODS: On a retrospective basis, we enrolled 170 newly diagnosed with or retreated for multidrug-resistant TB (MDR-TB) in 2004 from 21 private hospitals. We extracted the following demographics and treatment history from patient medical records: initial treatment outcomes, cumulative survival rates, treatment outcomes, and prognostic factors. RESULTS: Of the 170 patients, the majority were male (64.1%), the mean age was 44.5 years old, and mean body-mass-index was 20.2 kg/m2. None of the patients tested positive for HIV. Eleven (6.5%) were confirmed to have extensively drug-resistant TB (XDR-TB) at treatment initiation. Treatment success rates were not different between XDR-TB (36.4%, 4/11) and non-XDR MDR-TB (51.6%, 82/159). Default rate was high, 21.8% (37/170). Far advanced disease on X-ray was a significant negative predictor of treatment success; advanced disease and low BMI were risk factors for all-cause mortality. CONCLUSION: In private hospitals in Korea, the proportion of XDR-TB in MDR-TB was comparable to previous data. The treatment success rate of MDR-/XDR-TB remains poor and the failure rate was quite high. Adequate TB control policies should be strengthened to prevent the further development and spread of MDR-/XDR-TB in Korea.
Demography ; Extensively Drug-Resistant Tuberculosis ; HIV ; Hospitals, Private ; Humans ; Korea ; Male ; Public Health ; Retrospective Studies ; Risk Factors ; Survival Rate ; Tuberculosis, Multidrug-Resistant

Intramural hematoma of the cardiac muscle is a rare clinical condition. Only a few cases have been reported in the medicosurgical conditions related to post cardiac surgery, chest trauma and dissecting aneurysms of the aorta. Moreover, there are few cases of spontaneous left atrial intramural hematoma and they may occur in the medical conditions related to calcified mitral annulus dissection or amyloidosis. We experienced a case of spontaneous intramural left atrial hematoma in a 29 year-old male resulting in vaso-occlusive cardiogenic shock. We report the clinical manifestation and treatment of this case with a review of literatures.
Adult ; Amyloidosis ; Aneurysm, Dissecting ; Aorta ; Heart Atria ; Hematoma* ; Humans ; Male ; Myocardium ; Shock, Cardiogenic* ; Thoracic Surgery ; Thorax