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: The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection. Results: K18-hACE2 mice were intranasally infected with 1 × 105 PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7 days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection. Conclusion Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model.

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.

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.

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: This study aimed to investigate the association between e-cigarette (EC) use and development of acute severe pneumonia in the Korean population using a national database. Methods: We conducted a retrospective analysis using linkage of data between the Korean National Health and Nutrition Examination Survey (KNHANES) and the National Health Insurance Service (NHIS) administrative claims database. The primary endpoint of this study was development of severe pneumonia requiring hospital admission according to EC use during the study period. The secondary endpoints were in-hospital mortality, intensive care unit (ICU) admission, ventilator care, and days of hospital stay. Results: The final analysis included 28,950 individuals, of which 578 (2.0%) were EC users.EC users were younger and more often male than non-EC users. The EC users showed higher level of education and household income and had fewer comorbidities. Severe pneumonia was noted in 37 of 28,372 non-EC users (0.13%), but there were no occurrences of severe pneumonia in EC users. The incidence of pneumonia occurrence was not different between the two groups (P = 1.000). Conclusions Since e-cigarette or vaping use-associated lung injury (EVALI) is most likely included in acute severe pneumonia occurring within 3 months of EC use, it is considered that there might be no EVALI patients in Korea during the investigation period. A large-scale, prospective study is necessary to evaluate the association between EC use and acute lung injury.

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.

Materials and methods: A rigorous and systematic approach was used and each of the selected studies was evaluated for methodological quality. Data about study design, total number of cases enrolled, iron administration method, timing, and dose were extracted. Change in hemoglobin and transfusion rates were extracted to evaluate the effectiveness of iron supplementation. Results: Eleven studies were included in the final analysis. Most of studies reported that hemoglobin change between iron and control group did not show any difference. Only one study reported that iron supplementation could reduce the decrease in hemoglobin. However, transfusion rate showed a decrease in the iron supplementation group compared with the control group. There was no clear consensus on the optimum timing and dose of iron supplementation and intravenously administered iron was more effective than orally administered iron, especially in anemic patients. Conclusion Iron supplementation is not clear as a way to raise hemoglobin levels after TKA, but an effective treatment for lowering transfusion rate, especially in patients with anemia. We could not determine the optimal timing and dose of the iron. Intravenously administered iron was similar to, or better than, orally administered iron for improving hemoglobin levels and transfusion rate.

Materials and methods: A rigorous and systematic approach was used and each of the selected studies was evaluated for methodological quality. Data about study design, total number of cases enrolled, iron administration method, timing, and dose were extracted. Change in hemoglobin and transfusion rates were extracted to evaluate the effectiveness of iron supplementation. Results: Eleven studies were included in the final analysis. Most of studies reported that hemoglobin change between iron and control group did not show any difference. Only one study reported that iron supplementation could reduce the decrease in hemoglobin. However, transfusion rate showed a decrease in the iron supplementation group compared with the control group. There was no clear consensus on the optimum timing and dose of iron supplementation and intravenously administered iron was more effective than orally administered iron, especially in anemic patients. Conclusion Iron supplementation is not clear as a way to raise hemoglobin levels after TKA, but an effective treatment for lowering transfusion rate, especially in patients with anemia. We could not determine the optimal timing and dose of the iron. Intravenously administered iron was similar to, or better than, orally administered iron for improving hemoglobin levels and transfusion rate.