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Background@#Sleep apnea, characterized by interruptions in breathing during sleep, presents health risks and has been associated with various dietary patterns. This study aimed to investigate the relationship between dietary patterns, as measured by the Recommended Food Score (RFS), and the risk of sleep apnea, as assessed using the Berlin Questionnaire. @*Methods@#A total of 11,586 adults from a general hospital in Korea were included in the analysis. Participants completed a questionnaire covering demographic factors, lifestyle behaviors, and dietary habits. Dietary quality was assessed using the RFS, while sleep apnea risk was evaluated using the Berlin Questionnaire. Logistic regression analysis was conducted to assess the impact of RFS on sleep quality, adjusting for potential confounding factors. @*Results@#Higher RFS was negatively correlated with sleep apnea risk (odds ratio=0.91 [95% confidence interval, 0.82–1.00, P=0.048)]. Significant positive associations were observed between male sex, low education level, marital status, smoking, drinking, inactivity, high blood pressure, high waist circumference, high levels of triglycerides, and poor sleep quality. Hematologic markers such as C-reactive protein levels and glutamic pyruvic transaminase also displayed significant associations with sleep quality. @*Conclusions@#This study contributes to our understanding of the complex interplay between diet, lifestyle, metabolic health, and sleep quality. These findings underscore the importance of dietary interventions in managing sleep apnea and highlight avenues for further research.
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A survival prediction model has recently been developed to evaluate the prognosis of resected nonmetastatic pancreatic ductal adenocarcinoma based on a Cox model using two nationwide databases: Surveillance, Epidemiology and End Results (SEER) and Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP). In this study, we applied two machine learning methods—random survival forests (RSF) and support vector machines (SVM)—for survival analysis and compared their prediction performance using the SEER and KOTUS-BP datasets. Three schemes were used for model development and evaluation. First, we utilized data from SEER for model development and used data from KOTUS-BP for external evaluation. Second, these two datasets were swapped by taking data from KOTUS-BP for model development and data from SEER for external evaluation. Finally, we mixed these two datasets half and half and utilized the mixed datasets for model development and validation. We used 9,624 patients from SEER and 3,281 patients from KOTUS-BP to construct a prediction model with seven covariates: age, sex, histologic differentiation, adjuvant treatment, resection margin status, and the American Joint Committee on Cancer 8th edition T-stage and N-stage. Comparing the three schemes, the performance of the Cox model, RSF, and SVM was better when using the mixed datasets than when using the unmixed datasets. When using the mixed datasets, the C-index, 1-year, 2-year, and 3-year time-dependent areas under the curve for the Cox model were 0.644, 0.698, 0.680, and 0.687, respectively. The Cox model performed slightly better than RSF and SVM.
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Genetic associations have been quantified using a number of statistical measures. Entropy-based mutual information may be one of the more direct ways of estimating the association, in the sense that it does not depend on the parametrization. For this purpose, both the entropy and conditional entropy of the phenotype distribution should be obtained. Quantitative traits, however, do not usually allow an exact evaluation of entropy. The estimation of entropy needs a probability density function, which can be approximated by kernel density estimation. We have investigated the proper sequence of procedures for combining the kernel density estimation and entropy estimation with a probability density function in order to calculate mutual information. Genotypes and their interactions were constructed to set the conditions for conditional entropy. Extensive simulation data created using three types of generating functions were analyzed using two different kernels as well as two types of multifactor dimensionality reduction and another probability density approximation method called m-spacing. The statistical power in terms of correct detection rates was compared. Using kernels was found to be most useful when the trait distributions were more complex than simple normal or gamma distributions. A full-scale genomic dataset was explored to identify associations using the 2-h oral glucose tolerance test results and γ-glutamyl transpeptidase levels as phenotypes. Clearly distinguishable single-nucleotide polymorphisms (SNPs) and interacting SNP pairs associated with these phenotypes were found and listed with empirical p-values.
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Various methodologies for the genetic analysis of longitudinal data have been proposed and applied to data from large-scale genome-wide association studies (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with traits of interest and to detect SNP-time interactions. We recently proposed a grid-based Bayesian mixed model for longitudinal genetic data and showed that our Bayesian method increased the statistical power compared to the corresponding univariate method and well detected SNP-time interactions. In this paper, we further analyze longitudinal obesity-related traits such as body mass index, hip circumference, waist circumference, and waist-hip ratio from Korea Association Resource data to evaluate the proposed Bayesian method. We first conducted GWAS analyses of cross-sectional traits and combined the results of GWAS analyses through a meta-analysis based on a trajectory model and a random-effects model. We then applied our Bayesian method to a subset of SNPs selected by meta-analysis to further discover SNPs associated with traits of interest and SNP-time interactions. The proposed Bayesian method identified several novel SNPs associated with longitudinal obesity-related traits, and almost 25% of the identified SNPs had significant p-values for SNP-time interactions.
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The rise of newer coronavirus disease 2019 (COVID-19) variants has brought a challenge to ending the spread of COVID-19. The variants have a different fatality, morbidity, and transmission rates and affect vaccine efficacy differently. Therefore, the impact of each new variant on the spread of COVID-19 is of interest to governments and scientists. Here, we proposed mathematical SEIQRDVP and SEIQRDV3P models to predict the impact of the Omicron variant on the spread of the COVID-19 situation in South Korea. SEIQEDVP considers one vaccine level at a time while SEIQRDV3P considers three vaccination levels (only one dose received, full doses received, and full doses + booster shots received) simultaneously. The omicron variant’s effect was contemplated as a weighted sum of the delta and omicron variants’ transmission rate and tuned using a hyperparameter k. Our models’ performances were compared with common models like SEIR, SEIQR, and SEIQRDVUP using the root mean square error (RMSE). SEIQRDV3P performed better than the SEIQRDVP model. Without consideration of the variant effect, we don’t see a rapid rise in COVID-19 cases and high RMSE values. But, with consideration of the omicron variant, we predicted a continuous rapid rise in COVID-19 cases until maybe herd immunity is developed in the population. Also, the RMSE value for the SEIQRDV3P model decreased by 27.4%. Therefore, modeling the impact of any new risen variant is crucial in determining the trajectory of the spread of COVID-19 and determining policies to be implemented.
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Penalized regression has been widely used in genome-wide association studies for jointanalyses to find genetic associations. Among penalized regression models, the least absolute shrinkage and selection operator (Lasso) method effectively removes some coefficientsfrom the model by shrinking them to zero. To handle group structures, such as genes andpathways, several modified Lasso penalties have been proposed, including group Lasso andsparse group Lasso. Group Lasso ensures sparsity at the level of pre-defined groups, eliminating unimportant groups. Sparse group Lasso performs group selection as in group Lasso,but also performs individual selection as in Lasso. While these sparse methods are useful inhigh-dimensional genetic studies, interpreting the results with many groups and coefficients is not straightforward. Lasso's results are often expressed as trace plots of regressioncoefficients. However, few studies have explored the systematic visualization of group information. In this study, we propose a multi-level polar Lasso (MP-Lasso) chart, which caneffectively represent the results from group Lasso and sparse group Lasso analyses. An Rpackage to draw MP-Lasso charts was developed. Through a real-world genetic data application, we demonstrated that our MP-Lasso chart package effectively visualizes the resultsof Lasso, group Lasso, and sparse group Lasso.
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Various methods of frequent pattern mining have been applied to genetic problems, specifically, to the combined association of two genotypes (a genotype pattern, or diplotype) at different DNA variants with disease. These methods have the ability to come up with a selection of genotype patterns that are more common in affected than unaffected individuals, and the assessment of statistical significance for these selected patterns poses some unique problems, which are briefly outlined here.
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Objective@#The need to perform genetic sequencing to diagnose the polymerase epsilon exonuclease (POLE) subtype of endometrial cancer (EC) hinders the adoption of molecular classification. We investigated clinicopathologic and protein markers that distinguish the POLE from the copy number (CN)-low subtype in EC. @*Methods@#Ninety-one samples (15 POLE, 76 CN-low) were selected from The Cancer Genome Atlas EC dataset. Clinicopathologic and normalized reverse phase protein array expression data were analyzed for associations with the subtypes. A logistic model including selected markers was constructed by stepwise selection using area under the curve (AUC) from 5-fold cross-validation (CV). The selected markers were validated using immunohistochemistry (IHC) in a separate cohort. @*Results@#Body mass index (BMI) and tumor grade were significantly associated with the POLE subtype. With BMI and tumor grade as covariates, 5 proteins were associated with the EC subtypes. The stepwise selection method identified BMI, cyclin B1, caspase 8, and X-box binding protein 1 (XBP1) as markers distinguishing the POLE from the CN-low subtype. The mean of CV AUC, sensitivity, specificity, and balanced accuracy of the selected model were 0.97, 0.91, 0.87, and 0.89, respectively. IHC validation showed that cyclin B1 expression was significantly higher in the POLE than in the CN-low subtype and receiver operating characteristic curve of cyclin B1 expression in IHC revealed AUC of 0.683. @*Conclusion@#BMI and expression of cyclin B1, caspase 8, and XBP1 are candidate markers distinguishing the POLE from the CN-low subtype. Cyclin B1 IHC may replace POLE sequencing in molecular classification of EC.
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For the novel coronavirus disease 2019 (COVID-19), predictive modeling, in the literature, uses broadly susceptible exposed infected recoverd (SEIR)/SIR, agent-based, curve-fitting models. Governments and legislative bodies rely on insights from prediction models to suggest new policies and to assess the effectiveness of enforced policies. Therefore, access to accurate outbreak prediction models is essential to obtain insights into the likely spread and consequences of infectious diseases. The objective of this study is to predict the future COVID-19 situation of Korea. Here, we employed 5 models for this analysis; SEIR, local linear regression (LLR), negative binomial (NB) regression, segment Poisson, deep-learning based long short-term memory models (LSTM) and tree based gradient boosting machine (GBM). After prediction, model performance comparison was evelauated using relative mean squared errors (RMSE) for two sets of train (January 20, 2020‒December 31, 2020 and January 20, 2020‒January 31, 2021) and testing data (January 1, 2021‒February 28, 2021 and February 1, 2021‒February 28, 2021) . Except for segmented Poisson model, the other models predicted a decline in the daily confirmed cases in the country for the coming future. RMSE values’ comparison showed that LLR, GBM, SEIR, NB, and LSTM respectively, performed well in the forecasting of the pandemic situation of the country. A good understanding of the epidemic dynamics would greatly enhance the control and prevention of COVID-19 and other infectious diseases. Therefore, with increasing daily confirmed cases since this year, these results could help in the pandemic response by informing decisions about planning, resource allocation, and decision concerning social distancing policies.
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Objective@#Bipolar disorder (BD) is complex genetic disorder. Therefore, approaches using clinical phenotypes such as biological rhythm disruption could be an alternative. In this study, we explored the relationship between melatonin pathway genes with circadian and seasonal rhythms of BD. @*Methods@#We recruited clinically stable patients with BD (n=324). We measured the seasonal variation of mood and behavior (seasonality), and circadian preference, on a lifetime basis. We analyzed 34 variants in four genes (MTNR1a, MTNR1b, AANAT, ASMT) involved in the melatonin pathway. @*Results@#Four variants were nominally associated with seasonality and circadian preference. After multiple test corrections, the rs116879618 in AANAT remained significantly associated with seasonality (corrected p=0.0151). When analyzing additional variants of AANAT through imputation, the rs117849139, rs77121614 and rs28936679 (corrected p=0.0086, 0.0154, and 0.0092) also showed a significant association with seasonality. @*Conclusion@#This is the first study reporting the relationship between variants of AANAT and seasonality in patients with BD. Since AANAT controls the level of melatonin production in accordance with light and darkness, this study suggests that melatonin may be involved in the pathogenesis of BD, which frequently shows a seasonality of behaviors and symptom manifestations.
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Background/Aims@#Several prediction models for evaluating the prognosis of nonmetastatic resected pancreatic ductal adenocarcinoma (PDAC) have been developed, and their performances were reported to be superior to that of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. We developed a prediction model to evaluate the prognosis of resected PDAC and externally validated it with data from a nationwide Korean database. @*Methods@#Data from the Surveillance, Epidemiology and End Results (SEER) database were utilized for model development, and data from the Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP) database were used for external validation. Potential candidate variables for model development were age, sex, histologic differentiation, tumor location, adjuvant chemotherapy, and the AJCC 8th staging system T and N stages. For external validation, the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (AUC) were evaluated. @*Results@#Between 2004 and 2016, data from 9,624 patients were utilized for model development, and data from 3,282 patients were used for external validation. In the multivariate Cox proportional hazard model, age, sex, tumor location, T and N stages, histologic differentiation, and adjuvant chemotherapy were independent prognostic factors for resected PDAC. After an exhaustive search and 10-fold cross validation, the best model was finally developed, which included all prognostic variables. The C-index, 1-year, 2-year, 3-year, and 5-year time-dependent AUCs were 0.628, 0.650, 0.665, 0.675, and 0.686, respectively. @*Conclusions@#The survival prediction model for resected PDAC could provide quantitative survival probabilities with reliable performance. External validation studies with other nationwide databases are needed to evaluate the performance of this model.
ABSTRACT
For the novel coronavirus disease 2019 (COVID-19), predictive modeling, in the literature, uses broadly susceptible exposed infected recoverd (SEIR)/SIR, agent-based, curve-fitting models. Governments and legislative bodies rely on insights from prediction models to suggest new policies and to assess the effectiveness of enforced policies. Therefore, access to accurate outbreak prediction models is essential to obtain insights into the likely spread and consequences of infectious diseases. The objective of this study is to predict the future COVID-19 situation of Korea. Here, we employed 5 models for this analysis; SEIR, local linear regression (LLR), negative binomial (NB) regression, segment Poisson, deep-learning based long short-term memory models (LSTM) and tree based gradient boosting machine (GBM). After prediction, model performance comparison was evelauated using relative mean squared errors (RMSE) for two sets of train (January 20, 2020‒December 31, 2020 and January 20, 2020‒January 31, 2021) and testing data (January 1, 2021‒February 28, 2021 and February 1, 2021‒February 28, 2021) . Except for segmented Poisson model, the other models predicted a decline in the daily confirmed cases in the country for the coming future. RMSE values’ comparison showed that LLR, GBM, SEIR, NB, and LSTM respectively, performed well in the forecasting of the pandemic situation of the country. A good understanding of the epidemic dynamics would greatly enhance the control and prevention of COVID-19 and other infectious diseases. Therefore, with increasing daily confirmed cases since this year, these results could help in the pandemic response by informing decisions about planning, resource allocation, and decision concerning social distancing policies.
ABSTRACT
Objective@#Bipolar disorder (BD) is complex genetic disorder. Therefore, approaches using clinical phenotypes such as biological rhythm disruption could be an alternative. In this study, we explored the relationship between melatonin pathway genes with circadian and seasonal rhythms of BD. @*Methods@#We recruited clinically stable patients with BD (n=324). We measured the seasonal variation of mood and behavior (seasonality), and circadian preference, on a lifetime basis. We analyzed 34 variants in four genes (MTNR1a, MTNR1b, AANAT, ASMT) involved in the melatonin pathway. @*Results@#Four variants were nominally associated with seasonality and circadian preference. After multiple test corrections, the rs116879618 in AANAT remained significantly associated with seasonality (corrected p=0.0151). When analyzing additional variants of AANAT through imputation, the rs117849139, rs77121614 and rs28936679 (corrected p=0.0086, 0.0154, and 0.0092) also showed a significant association with seasonality. @*Conclusion@#This is the first study reporting the relationship between variants of AANAT and seasonality in patients with BD. Since AANAT controls the level of melatonin production in accordance with light and darkness, this study suggests that melatonin may be involved in the pathogenesis of BD, which frequently shows a seasonality of behaviors and symptom manifestations.
ABSTRACT
Purpose@#Diagnostic biomarkers of pancreatic ductal adenocarcinoma (PDAC) have been used for early detection to reduce its dismal survival rate. However, clinically feasible biomarkers are still rare. Therefore, in this study, we developed an automated multi-marker enzyme-linked immunosorbent assay (ELISA) kit using 3 biomarkers (leucine-rich alpha-2-glycoprotein [LRG1], transthyretin [TTR], and CA 19-9) that were previously discovered and proposed a diagnostic model for PDAC based on this kit for clinical usage. @*Methods@#Individual LRG1, TTR, and CA 19-9 panels were combined into a single automated ELISA panel and tested on 728 plasma samples, including PDAC (n = 381) and normal samples (n = 347). The consistency between individual panels of 3 biomarkers and the automated multi-panel ELISA kit were accessed by correlation. The diagnostic model was developed using logistic regression according to the automated ELISA kit to predict the risk of pancreatic cancer (high-, intermediate-, and low-risk groups). @*Results@#The Pearson correlation coefficient of predicted values between the triple-marker automated ELISA panel and the former individual ELISA was 0.865. The proposed model provided reliable prediction results with a positive predictive value of 92.05%, negative predictive value of 90.69%, specificity of 90.69%, and sensitivity of 92.05%, which all simultaneously exceed 90% cutoff value. @*Conclusion@#This diagnostic model based on the triple ELISA kit showed better diagnostic performance than previous markers for PDAC. In the future, it needs external validation to be used in the clinic.
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Background@#A coronavirus disease 2019 (COVID-19) outbreak started in February 2020 and was controlled at the end of March 2020 in Daegu, the epicenter of the coronavirus outbreak in Korea. The aim of this study was to describe the clinical course and outcomes of patients with COVID-19 in Daegu. @*Methods@#In collaboration with Daegu Metropolitan City and Korean Center for Diseases Control, we conducted a retrospective, multicenter cohort study. Demographic, clinical, treatment, and laboratory data, including viral RNA detection, were obtained from the electronic medical records and cohort database and compared between survivors and non-survivors. We used univariate and multi-variable logistic regression methods and Cox regression model and performed Kaplan–Meier analysis to determine the risk factors associated with the 28-day mortality and release from isolation among the patients. @*Results@#In this study, 7,057 laboratory-confirmed patients with COVID-19 (total cohort) who had been diagnosed from February 18 to July 10, 2020 were included. Of the total cohort, 5,467 were asymptomatic to mild patients (77.4%) (asymptomatic 30.6% and mild 46.8%), 985 moderate (14.0%), 380 severe (5.4%), and 225 critical (3.2%). The mortality of the patients was 2.5% (179/7,057). The Cox regression hazard model for the patients with available clinical information (core cohort) (n = 2,254) showed the risk factors for 28-day mortality: age > 70 (hazard ratio [HR], 4.219, P = 0.002), need for O 2 supply at admission (HR, 2.995; P = 0.001), fever (> 37.5°C) (HR, 2.808; P = 0.001), diabetes (HR, 2.119; P = 0.008), cancer (HR, 3.043; P = 0.011), dementia (HR, 5.252; P = 0.008), neurological disease (HR, 2.084; P = 0.039), heart failure (HR, 3.234;P = 0.012), and hypertension (HR, 2.160; P = 0.017). The median duration for release from isolation was 33 days (interquartile range, 24.0–46.0) in survivors. The Cox proportional hazard model for the long duration of isolation included severity, age > 70, and dementia. @*Conclusion@#Overall, asymptomatic to mild patients were approximately 77% of the total cohort (asymptomatic, 30.6%). The case fatality rate was 2.5%. Risk factors, including older age, need for O 2 supply, dementia, and neurological disorder at admission, could help clinicians to identify COVID-19 patients with poor prognosis at an early stage.
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With the ongoing rise of coronavirus disease 2019 (COVID-19) pandemic across the globe, interests in COVID-19 antibody testing, also known as a serology test has grown, as a way to measure how far the infection has spread in the population and to identify individuals who may be immune. Recently, many countries reported their population based antibody titer study results. South Korea recently reported their third antibody formation rate, where it divided the study between the general population and the young male youths in their early twenties. As previously stated, these simple point estimates may be misinterpreted without proper estimation of standard error and confidence intervals. In this article, we provide an updated 95% confidence intervals for COVID-19 antibody formation rate for the Korean population using asymptotic, exact and Bayesian statistical estimation methods. As before, we found that the Wald method gives the narrowest interval among all asymptotic methods whereas mid p-value gives the narrowest among all exact methods and Jeffrey’s method gives the narrowest from Bayesian method. The most conservative 95% confidence interval estimation shows that as of 00:00 November 23, 2020, at least 69,524 people were infected but not confirmed. It also shows that more positive cases were found among the young male in their twenties (0.22%), three times that of the general public (0.051%). This thereby calls for the quarantine authorities’ need to strengthen quarantine managements for the early 20s in order to find the hidden infected people in the population.
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In genome-wide association studies, pathway-based analysis has been widely performed to enhance interpretation of single-nucleotide polymorphism association results. We proposed a novel method of hierarchical structural component model (HisCoM) for pathway analysis of common variants (HisCoM for pathway analysis of common variants [HisCoM-PCA]) which was used to identify pathways associated with traits. HisCoM-PCA is based on principal component analysis (PCA) for dimensional reduction of single nucleotide polymorphisms in each gene, and the HisCoM for pathway analysis. In this study, we developed a HisCoM-PCA software for the hierarchical pathway analysis of common variants. HisCoM-PCA software has several features. Various principle component scores selection criteria in PCA step can be specified by users who want to summarize common variants at each gene-level by different threshold values. In addition, multiple public pathway databases and customized pathway information can be used to perform pathway analysis. We expect that HisCoM-PCA software will be useful for users to perform powerful pathway analysis.
ABSTRACT
The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. No specific therapeutic agents or vaccines for COVID-19 are available, though several antiviral drugs, are under investigation as treatment agents for COVID-19. The use of convalescent plasma transfusion that contain neutralizing antibodies for COVID-19 has become the major focus. This requires mass screening of populations for these antibodies. While several countries started reporting population based antibody rate, its simple point estimate may be misinterpreted without proper estimation of standard error and confidence intervals. In this paper, we review the importance of antibody studies and present the 95% confidence intervals COVID-19 antibody rate for the Korean population using two recently performed antibody tests in Korea. Due to the sparsity of data, the estimation of confidence interval is a big challenge. Thus, we consider several confidence intervals using Asymptotic, Exact and Bayesian estimation methods. In this article, we found that the Wald method gives the narrowest interval among all Asymptotic methods whereas mid p-value gives the narrowest among all Exact methods and Jeffrey’s method gives the narrowest from Bayesian method. The most conservative 95% confidence interval estimation shows that as of 00:00 on September 15, 2020, at least 32,602 people were infected but not confirmed in Korea.
ABSTRACT
In genome-wide association studies, pathway-based analysis has been widely performed to enhance interpretation of single-nucleotide polymorphism association results. We proposed a novel method of hierarchical structural component model (HisCoM) for pathway analysis of common variants (HisCoM for pathway analysis of common variants [HisCoM-PCA]) which was used to identify pathways associated with traits. HisCoM-PCA is based on principal component analysis (PCA) for dimensional reduction of single nucleotide polymorphisms in each gene, and the HisCoM for pathway analysis. In this study, we developed a HisCoM-PCA software for the hierarchical pathway analysis of common variants. HisCoM-PCA software has several features. Various principle component scores selection criteria in PCA step can be specified by users who want to summarize common variants at each gene-level by different threshold values. In addition, multiple public pathway databases and customized pathway information can be used to perform pathway analysis. We expect that HisCoM-PCA software will be useful for users to perform powerful pathway analysis.
ABSTRACT
The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. No specific therapeutic agents or vaccines for COVID-19 are available, though several antiviral drugs, are under investigation as treatment agents for COVID-19. The use of convalescent plasma transfusion that contain neutralizing antibodies for COVID-19 has become the major focus. This requires mass screening of populations for these antibodies. While several countries started reporting population based antibody rate, its simple point estimate may be misinterpreted without proper estimation of standard error and confidence intervals. In this paper, we review the importance of antibody studies and present the 95% confidence intervals COVID-19 antibody rate for the Korean population using two recently performed antibody tests in Korea. Due to the sparsity of data, the estimation of confidence interval is a big challenge. Thus, we consider several confidence intervals using Asymptotic, Exact and Bayesian estimation methods. In this article, we found that the Wald method gives the narrowest interval among all Asymptotic methods whereas mid p-value gives the narrowest among all Exact methods and Jeffrey’s method gives the narrowest from Bayesian method. The most conservative 95% confidence interval estimation shows that as of 00:00 on September 15, 2020, at least 32,602 people were infected but not confirmed in Korea.