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.

Lactase non-persistence (LNP), one of the causes of lactose intolerance, is related to lactase gene associated single nucleotide polymorphisms (SNPs). Since the frequency of LNP varies by ethnic group and country, the research to reveal the presence or absence of LNP for specific people has been conducted worldwide. However, in East Asia, the study of lactase gene associated SNPs have not been sufficiently examined so far using ancient human specimens from archaeological sites. In our study of Joseon period human remains (n=14), we successfully revealed genetic information of lactase gene associated SNPs (rs1679771596, rs41525747, rs4988236, rs4988235, rs41380347, rs869051967, rs145946881 and rs182549), further confirming that as for eight SNPs, the pre-modern Korean people had a lactase non-persistent genotype. Our report contributes to the establishment of LNP associated SNP analysis technique that can be useful in forthcoming studies on human bones and mummy samples from East Asian archaeological sites.

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.

Purpose: Triage tools play a vital role in classifying the severity of children in emergency departments (EDs). We investigated the association between the Korean Triage and Acuity Scale (KTAS) and severity of dyspnea in the ED. Methods: We conducted a retrospective study of children aged 3-14 years with dyspnea who visited the ED from January 2015 through December 2021. They were divided into severe (KTAS level 1-3) and non-severe (KTAS level 4-5) groups. Between the groups, we compared the clinical characteristics, including age, sex, associated symptoms, vital signs, route of visit, treatment at ED, and outcomes. Results: Among a total of 468 children with dyspnea, 267 and 201 were assigned to the severe and non-severe groups, respectively. The severe group had higher frequencies of fever (21.7% vs. 13.9%; P = 0.031), cough (53.2% vs. 43.3%; P = 0.034), systemic steroids (42.3% vs. 25.9%; P < 0.001), intravenous fluids (47.6% vs. 25.4%; P < 0.001), oxygen therapy (16.5% vs. 6.5%; P = 0.001), inotropics (4.1% vs. 1.0%; P = 0.042), and hospitalization (24.7% vs. 11.9%; P = 0.002). The severe group also showed a higher mean heart rate, respiratory rate, and temperature, and lower mean oxygen saturation (all Ps < 0.001). Among these findings, fever, heart rate, respiratory rate, temperature, intravenous fluids, oxygen therapy, inotropics, and hospitalization remained significantly different between the groups after defining the severe group as a KTAS level 1-2. Conclusion This study shows the association between KTAS and severity of dyspnea in the ED. Therefore, KTAS may reflect not only the initial clinical conditions but also emergency measures and outcomes in children with dyspnea who visit EDs.

Objective: A prolonged length of stay in the emergency department (EDLOS) is known to be associated with poorer outcomes in critically ill patients. However, this has not been proven in patients who visit the emergency department (ED) due to acute heart failure (AHF). We aimed to find out whether prolonged EDLOS is associated with major in-hospital complications in patients with AHF. Methods: This is a retrospective cohort study of AHF patients who were admitted to intensive care units (ICU) via the ED of a single academic hospital from January 2015 to December 2019. We divided the patients into two groups: EDLOS <24 hours and EDLOS≥24 hours. The primary outcome was major in-hospital complications, which included in-hospital death, application of continuous renal replacement therapy, or extracorporeal membrane oxygenation treatment. Secondary outcomes included in-hospital death, prolonged ICU stay (≥10 days), and prolonged hospital stay (≥14 days) excluding ED stay. Results: A total of 265 patients were enrolled. Of these 163 patients stayed in the ED for over 24 hours. The multivariable logistic analysis demonstrated that EDLOS ≥24 hours was independently associated with major in-hospital complications (odds ratio [OR], 3.296; 95% confidence interval [CI], 1.291-8.413; P=0.013). Analysis of the secondary outcomes showed that EDLOS ≥24 hours was associated with in-hospital death (OR, 2.607; 95% CI, 1.005-6.759; P=0.049) and prolonged hospital stay ≥14 days (OR, 2.458; 95% CI, 1.303-4.636; P=0.006). Conclusion Our study showed that in patients with AHF who visited ED and were admitted to the ICU, prolonged EDLOS was associated with major in-hospital complications.

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.

We evaluated the Standard Q COVID-19 Ag test for the diagnosis of coronavirus disease 2019 (COVID-19) compared to the reverse transcription-polymerase chain reaction (RT-PCR) test.We applied both tests to patients who were about to be hospitalized, had visited an emergency room, or had been admitted due to COVID-19 confirmed by RT-PCR. Two nasopharyngeal swabs were obtained; one was tested by RT-PCR and the other by the Standard Q COVID-19 Ag test. A total of 118 pairs of tests from 98 patients were performed between January 5 and 11, 2021. The overall sensitivity and specificity for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for the Standard Q COVID-19 Ag test compared to RT-PCR were 17.5% (95% confidence interval [CI], 8.8–32.0%) and 100% (95% CI, 95.3–100.0%). Analysis of the results using RT-PCR cycle thresholds of ≤ 30 or ≤ 25 increased the sensitivity to 26.9% (95% CI, 13.7–46.1%), and 41.1% (95% CI, 21.6–64.0%), respectively.

Background: Cervical cancer is the fourth common cancer in women worldwide. The Papanicolau test is the primary screening procedure to detect abnormal cervical cells.Colposcopy is the main procedure for discriminating high-grade cervical lesions. The study aimed at clarifying the discrepancy between cervical cytology and colposcopic biopsy histology as well as confounding factors. Methods: Eligible patients visited thirteen tertiary hospitals for colposcopic biopsy following cervical cytology and human papillomavirus (HPV) genotypes between January and December 2018. Baseline characteristics including age, body mass index (BMI), and parity were collected. Results: In our study, 3,798 eligible patients were included. Mean age of patients was 42.7(19–88) years and mean BMI was 22.5 (16.9–34.1) kg/m2 . The referred cervical cytologic findings consisted of 495 normal, 1,390 atypical squamous cells of undetermined significance, 380 atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion, 792 low-grade squamous intraepithelial lesion, 593 high-grade squamous intraepithelial lesion, 79 atypical glandular cells, 46 squamous cell carcinoma, and 23 adenocarcinoma. HPV-positive findings were found in 3,008 (79.2%) patients and were not detected in 914 (24.1%) cases. The risk of unexpected low-grade lesions from histology was higher in patients > 45 years (odds ratio [OR], 2.137; 95% confidence intervals [CIs], 1.475–3.096). In contrast, the risk of unexpected high-grade lesions from colposcopic biopsy was lower in patients ≥ 45 years (OR, 0.530; 95% CI, 0.367–0.747) and HPV 16/18 infection was higher than other HPV (OR, 1.848; 95% CI, 1.385–2.469). Conclusion Age and HPV genotypes were responsible for the discrepancies between cytology and histology. Precautions should be taken for women over the age of 45 in triage for colposcopy in order to avoid unnecessary testing.

Purpose: The prognostic factors in obstructive colon cancer have not been clearly identified. We aimed to identify the prognostic factor to establish optimal treatment strategy in obstructive colon cancer. Methods: Patients who underwent surgery for primary colon cancer in stages II and III with symptomatic obstruction from 2004 to 2010 in six hospitals were retrospectively collected. Clinicopathological and surgical outcomes were compared between stent insertion and emergent surgery group. Multiple regression analysis and survival curve analysis were used to identif y the prognostic factors in symptomatic obstructive colon cancer. Results: Among 210 patients, 168 patients (80.0%) underwent stent insertion followed by surgery and 42 patients (20.0%) underwent emergent surgery. Laparoscopic approach (55.4% vs. 23.8%, p< 0.001) and adequate lymph node (LN) harvest (≥12) (93.5% vs. 69.0%, p < 0.001) were significantly higher in stent insertion group. In multiple regression analysis, emergent surgery (hazard ratio [HR], 2.153; 95% confidence interval [CI], 1.031–4.495), vascular invasion (HR, 6.257; 95% CI, 2.784–14.061), and omitting adjuvant chemotherapy (HR, 3.107; 95% CI, 1.394–6.925) were independent poor prognostic factors in 5-year overall survival, and N stage (N1: HR, 3.095; 95% CI, 1.316–7.284; N2: HR, 4.156; 95% CI, 1.671–10.333) was the only poor prognostic factor in 5-year disease-free survival. Conclusion In symptomatic obstructive colon cancer, emergent surgery, N stage, vascular invasion, and omission of adjuvant chemotherapy were independent poor prognostic factors. Stent insertion is suggested as the initial treatment for symptomatic obstructive colon cancer, and adjuvant chemotherapy is recommended, especially when vascular invasion or LN metastasis is confirmed.