A Study on the Retrospective Reinterpretation of BRCA1 and BRCA2 Variants.

BACKGROUND: Hereditary breast/ovarian cancer is associated with BRCA gene mutations. As large volumes of clinical data on BRCA variants are continuously updated, their clinical interpretation may change, leading to their reclassification. This study analyzed the class and proportion of the changed clinical interpretations of BRCA variants to validate the need for periodic reviews of these variants. METHODS: This retrospective study reinterpreted previously reported BRCA1 and BRCA2 exon variants according to the 2015 American College of Medical Genetics and Genomics guidelines and the clinical significance of the recent public genomic database. Reanalyzed results were obtained for patients tested for BRCA genetic mutation for 10 years and 4 months. RESULTS: We included data from 4,058 patients, with 595 having at least one pathogenic variant (P), likely pathogenic variant (LP), or variant of uncertain significance (VUS) at a detection rate of 14.66%. The numbers of exon and intron variants were 562 (87.81%) and 78 (12.19%), respectively. BRCA1 exhibited a significantly higher P/LP detection rate of 6.96% compared to that of BRCA2 at 6.89% (p < 0.001). Conversely, BRCA2 demonstrated a significantly higher VUS rate of 10.38% compared to that of BRCA1 at 5.08% (p < 0.001). Among BRCA1 mutations, substitutions were the most prevalent in P/LP and VUS. Among BRCA2 mutations, deletions were most prevalent in P/LP, and substitutions were most prevalent in VUS. Among the 131 patients with P/LP in BRCA1 exons, the clinical interpretation was reclassified in two cases (1.53%), one VUS and one benign/likely benign (B/LB), and 48 cases (48.00%) with VUS were reclassified; one to P/LP and 47 to B/LB. Among the 138 patients with P/LP in BRCA2 exons, the clinical interpretation was reclassified in six (4.35%), five to VUS, and one to B/LB, and all 74 with VUS were reclassified to B/LB. CONCLUSIONS: We determined the class and proportion of reclassified BRCA variants. In conclusion, reviews are required to provide clinical guidance, such as determining treatment direction and preventive measures in the future.

Circulating-tumor DNA Assessment in Diffuse Large B-cell Lymphoma to Determine Up-front Stem Cell Transplantation: A Pilot Study.

BACKGROUND/AIM: This study evaluated the possibility of clinical use of circulating-tumor DNA (ctDNA) as a biomarker to determine up-front autologous stem cell transplantation (auto-SCT) for patients with high-risk diffuse large B-cell lymphoma (DLBCL) in practice. PATIENTS AND METHODS: To explore the dynamics of ctDNA in DLBCL, blood samples were collected sequentially before and after treatment from patients with newly diagnosed DLBCL who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. To conduct ctDNA genotyping and ctDNA monitoring simultaneously, targeted sequencing by cancer personalized profiling using deep sequencing was used. RESULTS: Ten patients between the ages of 50 and 60 years were enrolled. Based on the international prognostic index (IPI), seven patients were classified as high-IPI-risk group, and three patients were classified as low-IPI-risk group. The IPI risk group correlated with total metabolic tumor volume. All patients completed six cycles of R-CHOP chemotherapy, and seven patients achieved complete response. Changes in ctDNA mutation numbers did not correlate with changes in PET scan images and treatment response. In most high-risk patients, new mutations appeared in ctDNA after completion of chemotherapy that conceivably marked resistant clones. Notably, disease relapse did not occur in high-risk patients with poor prognostic mutations who underwent autologous SCT. CONCLUSION: ctDNA monitoring was meaningful in high-risk patients. Moreover, ctDNA and well-known prognostic factors should be considered in the decision making for auto-SCT. If a new genetic mutation in ctDNA with a negative prognosis would emerge during treatment, high-risk patients should consider auto-SCT.

Incidence and Distribution of the Pathogens Causing GI Infections at a University Hospital of Korea.

BACKGROUND: Gastrointestinal (GI) infections, caused by various pathogens such as bacteria, viruses, protozoa, and parasites, are the second most common infectious diseases. Molecular diagnostics that can simultaneously detect these pathogens are commonly used in syndromic approaches. The authors aimed to identify the causative pathogens of GI infections to provide clinically useful information. METHODS: This retrospective study used molecular diagnostic methods to determine the incidence and distribution of GI pathogens according to gender, age, and season and analyze their coinfection from August 2020 to December 2022. RESULTS: The overall incidence of at least one GI pathogen was 40.1% (991/2, 471). The positivity rates for bacteria and viruses were 33.1% (817/2, 471) and 9.2% (227/2,471), respectively; the positivity rate for bacteria was significantly higher than that for viruses (p < 0.001). The incidence of GI pathogens according to age group was highest in group 3 (59.9%), followed by group 4 (57.0%). The most common bacterial pathogen associated with GI infections was C. difficile, followed by diarrheagenic E. coli, Campylobacter spp., and Salmonella spp. Enteropathogenic E. coli accounted for a large percentage of diarrheagenic E. coli (63.6%, 157/247). Among the viral pathogens, norovirus GI/GII was the most commonly detected virus, followed by adenovirus F40/41 and rotavirus A. For bacterial- or viral-positive cases, the distribution of GI pathogens according to age group showed the highest proportion of C. difficile in all groups, except for group 2. In group 2, rotavirus A accounted for the highest percentage (61.1%, 22/36). The incidence of GI pathogens was the highest in summer (36.1%), followed by autumn (32.7%), and winter (18.0%). The co-infection rate with two or more pathogens was 16.9% (167/991). The rates of co-infection with two or more bacteria, bacteria and viruses, and two viruses were 58.1%, 31.7%, and 10.2%, re-spectively. CONCLUSIONS: Information on the incidence and distribution of GI pathogens might be clinically useful; however, unlike the distribution of other infectious pathogens, it is necessary to consider that microorganisms identified through molecular diagnostics can be detected even in healthy people without clinical symptoms.

Recent Changes in the Human Metapneumovirus Outbreak at a University Hospital in Korea.

BACKGROUND: Although the detection of respiratory viruses other than severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was significantly reduced because of quarantine due to the coronavirus disease (COVID-19) pandemic, an epidemic of several viruses was reported unexpectedly. We also detected a change in the pattern of human metapneumovirus (HMPV) outbreak compared to that before the COVID-19 pandemic. Therefore, the authors intended to identify the incidence and altered distribution pattern of the HMPV outbreak and provide useful information for clinical practice. METHODS: This retrospective study investigated the incidence and distribution of HMPV from March 2020 to December 2022 during the COVID-19 pandemic. Detection of respiratory microorganisms was performed by multiplex polymerase chain reaction using a commercial kit and FilmArray assay. RESULTS: The overall incidence of at least one respiratory microorganism was 50.3% (1,152/2,290). HMPV was not detected between March 2020 and June 2022. However, it was suddenly detected in July 2022 and continued for approximately five months until November 2022. In particular, the detection rate of HMPV was high in September and October 2022, accounting for approximately 76.1% (51/67) of the total HMPV-positive cases. Seasonally, 92.5% (62/67) of HMPV cases were detected in autumn, while the rest of the cases were detected in summer. The HMPV detection rate, according to the age group, was highest in group 4 (3 - 6 years) at 7.4% (27/367), followed by group 3 (4 months to 2 years) at 3.6% (31/861). In HMPV-positive cases, the rate of more than two respiratory pathogens was 46.3% (31/67). An analysis of co-infecting pathogens showed that HMPV with rhinovirus A/B/C/ enteroviruses accounted for the highest percentage (51.6%), followed by HMPV with respiratory syncytial virus (48.4%). CONCLUSIONS: The COVID-19 pandemic has caused several changes in our lives. This study confirmed that the seasonal distribution of HMPV was different from that before the COVID-19 pandemic. Therefore, it can be assumed that the distribution of other respiratory microorganisms could have changed and it appears that changes could occur in previously known viral epidemiology. Clinicians should therefore be alert to this possibility.

The Diagnostic Yield and Difficulties of Utilizing Soft-clipped Read Clusters Encountered in Clinical Exome Sequencing.

BACKGROUND: Despite the wide use of next generation sequencing, there are still many difficulties in detecting structural variants. A split read is one of the clues of structural variants and is represented as a soft-clipped read in the raw sequencing data. Considering that most of the breakpoints of structural variants reside in non-coding regions, split read information has not been routinely used in exome sequencing or targeted panel sequencing. Recently, SCRAMble, a software capable of detecting mobile element insertion (MEI) and deletion based on soft-clipped read clusters (SCRCs), was shown to provide an additional diagnostic yield of 0.03 - 0.25%. SCRAMble is the only software that can be used for exome sequencing or targeted panel sequencing to detect structural variants based on SCRC information. The aim of present study was to establish a working procedure of utilizing SCRC information using SCRAMble in clinical exome sequencing and to assess its diagnostic yield. METHODS: Raw sequencing data of clinical exome sequencing were retrospectively analyzed using SCRAMble to search MEIs and deletions. SCRAMble software was installed according to the manufacturer's instructions and default parameters except for one, mei-score, which was adjusted for sensitivity, were used. RefSeq gene annotation was performed for both MEI and deletion calls using ANNOVAR. Blacklist-based filtering was used to reduce candidate MEI/deletion calls. Clinical relevance was manually evaluated for the remaining variant calls. RESULTS: One diagnostic MEI, which is a founder variant in East Asia, was detected in two cases (2/266, 0.75%). In addition, two diagnostic deletions, which had been previously detected in depth-of-coverage (DOC)-based copy number variant (CNV) callers, were detected (2/266, 0.75%). Base-level breakpoints that could not be derived by the DOC-based callers were identified for these two deletions using SCRAMble. Most SCRCs were repetitive among cases and blacklist-based filtering reduced candidate MEI/deletion calls by 49.5 - 94.5%, leaving a considerable number of variant calls to be manually validated. CONCLUSIONS: SCRC screening in exome or targeted panel sequencing may provide additional diagnostic yield either by pathogenic MEI detection or reassurance of deletions identified by DOC-based CNV callers. Development of an efficient filtering algorithm is warranted.

Diagnostic Performance of Interferon Gamma Release Assay (IGRA) for Cell-Mediated Immune Responses to SARS-CoV-2.

BACKGROUND: As SARS-CoV-2 infection became a pandemic, much effort has been made to measure both antibody production and T cell response to SARS-CoV-2 to diagnose COVID-19 patients or find out their immune status. Authors tried to determine the optimal cutoff value and evaluate clinical performance of one interferon-γ release assay (IGRA) kit and compared their results with serological antibody assay in COVID-19 patients. METHODS: Study subjects included 100 patients confirmed as COVID-19 with RT-PCR method and 88 healthy volunteers who were PCR negative. IGRA tests were performed using STANDARDTM E Covi-FERON ELISA. Presence of SARS-CoV-2 antibodies was detected using STANDARD Q COVID-19 IgM/IgG Plus Test. Cutoff value was assessed using receiver operating characteristic (ROC) curve. RESULTS: The cutoff value was 0.24 IU/mL and the area under the curve (AUC) of the ROC curve was 0.973 with 95% confidence interval (CI) of 0.940 - 1.005. At this cutoff value, sensitivity and specificity were 91.7% and 100%, respectively. In addition, when compared with antibody test, concordance rate was 95%. CONCLUSIONS: STANDARDTM E Covi-FERON ELISA showed high sensitivity and specificity, when the cutoff value was 0.24 IU/mL. It was also consistent with the antibody test. IGRA test was a good indicator of cellular immune response in COVID-19 patients.

Evaluation of two SARS-CoV-2 IgG/IgM Rapid Tests in Capillary Blood Samples.

BACKGROUND: As COVID-19 has spread rapidly around the world, it has become essential to detect the virus quickly and accurately for disease prevention and control. Therefore, in response to the COVID-19 pandemic, the need for rapid serological point-of-care test has increased. Recently, many antibody tests have been developed to detect IgM and/or IgG to SARS-CoV-2 in human blood. The authors conducted a prospective study to evaluate the performance of a rapid chromatographic immunoassay and a fluorescent immunoassay for the qualitative detection of specific antibodies, IgM and IgG to SARS-CoV-2 in capillary blood samples, compared to the real-time RT-PCR. METHODS: The subjects included 70 patients who were confirmed positive by real-time RT-PCR and 70 people who were negative. STANDARD Q COVID-19 IgM/IgG Plus Test (chromatographic immunoassay) and Fluorescent immunoassay for IgM and IgG to SARS-CoV-2 (fluorescent immunoassay) were performed using capillary blood samples. Based on the results of real-time RT-PCR assay, clinical sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of two rapid tests were investigated. And the agreement rate between two rapid tests was also presented. RESULTS: Sensitivity, specificity, PPV and NPV of the chromatographic immunoassay were 82.9%, 98.6%, 98.3%, and 85.2%, respectively. At more than 7 days after the onset of symptoms, sensitivity increased to 87.3%. Sensitivity, specificity, PPV, and NPV were 81.4%, 100.0%, 100.0%, and 84.3%, respectively, for the fluorescent immunoassay. At more than 7 days after the onset of symptoms, sensitivity increased to 85.7%. The agreement rate of the two tests was 97.1%. CONCLUSIONS: STANDARD Q COVID-19 IgM/IgG Plus Test and STANDARD F COVID-19 IgM/IgG Combo FIA turned out very specific and sensitive enough to detect individuals infected to SARS-CoV-2. Also, these tests were simple, fast, visually interpretable, and required a small amount of capillary whole blood.

Outbreak of Parainfluenza Virus During the COVID-19 Pandemic at a University Hospital in Korea.

BACKGROUND: The incidence of respiratory viral diseases including parainfluenza virus (PIV) infection has decreased noticeably due to strict quarantine measures during the COVID-19 pandemic. However, the recent outbreak of PIV in children occurred unexpectedly and the distribution pattern showed prominent differences from before the COVID-19 pandemic. PIV is one of the major viral pathogens related to acute lower respiratory infection in young children and the elderly. Accordingly, the authors intended to identify the incidence and distribution pattern of PIV outbreaks and to contribute to public health by providing information on it. METHODS: This study was conducted retrospectively to investigate the incidence and distribution of PIV according to age group, gender, month, and season, and to analyze the co-infections from March 2020 to February 2022. The detection for respiratory microorganisms was performed through FilmArray assay. RESULTS: The overall incidence for at least one respiratory pathogen was 45.9% (665/1,450). PIV was not detected at all from March 2020 to August 2021. However, it was first detected in September 2021 and the rate in the month that followed, October, accounted for 60% (114/190) of the total PIV infections during the entire study period. It also accounted for 44.9% (190/423) of patients with respiratory pathogens from September 2021 to February 2022. It reached the highest proportion at 90.5% (114/126) in October 2021. As for the distribution according to the age groups, group 3 (58.4%) accounted for the highest percentage, followed by group 4 (21.1%). In the PIV positive cases, the overall rate of more than two respiratory pathogens was 32.6% (62/190). The most common pattern of co-infection was PIV3 with rhinovirus/enterovirus (67.7%), followed by PIV3 with adenovirus (8.1%) and PIV3 with rhinovirus/enterovirus and adenovirus (8.1%). CONCLUSIONS: The COVID-19 pandemic has brought about many changes in our daily lives. It has been confirmed that the seasonal distribution of PIV was distinctly different from before the COVID-19 pandemic. It is anticipated that this phenomenon will affect the incidence or distribution of other respiratory pathogens and viral epidemiology. Therefore, clinicians should pay attention to these changes in terms of public health.

Prevalence of Group B Streptococcus Colonization in Pregnant Women at a University Hospital in Korea.

BACKGROUND: Group B Streptococcus (GBS) colonization in pregnant women is a risk factor for causing infection in neonates; therefore, GBS screening tests are performed on them. Culture methods and molecular diagnostics are mainly performed for GBS detection; however, culture methods differ in the detection rate for GBS depending on the procedure of culture. The authors intended to confirm the difference in GBS colonization rate in the conventional culture method, enrichment culture method, and molecular genetic test as screening tests for GBS. METHODS: Duplicate vagino-rectal swabs were collected from 371 pregnant women between the 35th and 37th week of gestation; one was used for conventional culture method and the other was frozen at -80℃, followed by enrichment culture method and molecular genetic test. RESULTS: The prevalence of GBS colonization identified by conventional culture, enrichment culture, and molecular genetic test was 4.35% (17/391), 8.95% (35/391), and 22.25% (87/391), respectively. The detection rate by enrichment culture method was 2.06 times higher (17/391 vs. 35/391) than that by conventional culture method. It was identified that there was a significant difference in the detection rates of GBS between the two methods (p < 0.001). The detection rate identified in molecular genetic test was much higher at 22.25% (87/391). The concordance rate of the results from three detection methods for GBS was 80.05% (313/391). All pregnant women colonized with GBS were given intrapartum antibiotic prophylaxis using cefazolin and their neonates were confirmed not to be infected with GBS. CONCLUSIONS: Prevalence of GBS colonization in pregnant women is shown to vary depending on detection method. Particularly, it differs greatly depending on the use of enrichment media in the culture method. Therefore, it is necessary that the microbiological laboratory implements the culture method with supplementary procedures such as selective or enrichment media in order to improve the detection rate of GBS.

Analysis of the fluid contents of simple bone cyst in the mandible.

Description of simple bone cyst (SBC) content has been controversial. This study aimed to assess and give a clearer picture of the SBC cavity contents. Between 2014 and 2016, 19 patients with SBC verified by histopathological examination were included in this study. SBC cavity content was investigated using clinical, radiographic, surgical, and laboratory findings. The difference in components among cavity fluid, blood, and serum was evaluated using a paired sample t-test for statistical analysis. All 19 SBC cases radiographically and surgically revealed a fluid-filled cavity. The patients' average age was 21.3 ± 13.2 years, with no sex predominance found. SBCs were found mostly in the anterior mandible (n = 12, 63.2%). All lesions were filled with clear straw-colored or blood-colored floods with low concentration. Although the fluid components were similar to those in the blood and serum in the laboratory analysis, the statistical analysis revealed that the fluid components were not significantly different only for eosinophil (p = 0.43) and basophil (p = 0.06) counts as blood components and sodium (p = 0.76), potassium (p = 0.08), and chloride (p = 0.13) concentration as serum components. The results show that SBC is a fluid-filled cavity, with the cavity fluid being more likely similar to serum rather than blood regarding internal components.

Feasibility of targeted cascade genetic testing in the family members of BRCA1/2 gene pathogenic variant/likely pathogenic variant carriers.

The pathogenic variant (PV) or likely pathogenic variant (LPV) BRCA1/2 gene is strongly associated with hereditary breast or ovarian cancer. Therefore, it is important to screen blood relatives to establish preventive modalities and surveillance. This study evaluated the feasibility of targeted cascade genetic testing for family members of BRCA1/2 gene PV or LPV carriers. We screened 18 families for BRCA1/2 gene status via the conventional cascade genetic test (n = 9) and targeted cascade genetic test (n = 9), which targeted the exon region wherein the index patient showed PV or LPV. The pedigree and clinicopathologic characteristics were reviewed and analyzed. All index patients were diagnosed with breast cancer, while the third family members were all healthy. In the conventional cascade test group, 3 index patients and 3 family members had the BRCA1/2 gene PV or LPV. In the targeted cascade test group, 5 family members had same type of BRCA1/2 gene PV or LPV as their index patients. Two families had an identical string of BRCA1/2 gene PV or LPV. Although the targeted cascade genetic test cannot completely characterize the BRCA1/2 gene, it is sufficient for determining its PV or LPV status. This limited genetic test can be used for family members of PV or LPV carriers.

Changes in the Distribution of Respiratory Microorganisms before and during the COVID-19 Pandemic, Daegu, Korea.

BACKGROUND: Acute respiratory infection (ARI) is the most common infectious disease in all ages and genders worldwide. Respiratory microorganisms such as respiratory viruses, are commonly responsible for causing ARI. COVID-19 is still prevalent in Korea. The implementation of lockdown and strict control measures, the mandatory wearing of masks, and social distancing are critical steps for controlling the risk of COVID-19 spread. This study was conducted to find out how these changes in daily lives impacted the distribution of respiratory microorganisms. METHODS: A retrospective study was conducted to identify the incidence and distribution patterns of ARI-causing respiratory microorganisms before (Period Ⅰ) and during the COVID-19 pandemic (Period Ⅱ) in terms of detection method, age, month, and season. In particular, data in Periods Ⅰ and Ⅱ were compared for eight major kinds of respiratory microorganisms: adenovirus (AdV), human metapneumovirus (HMPV), human rhinovirus/enterovirus (Rhino/Entero), influenza virus (Flu) A, Flu B, human parainfluenza virus (HPIV) 3, respiratory syncytial virus, and Mycoplasma pneumoniae. RESULTS: A total of 27,191 respiratory specimens were tested, of which 5,513 were obtained from children and adolescents (age groups 1 ⁓ 5) and 21,678 from adults (age group 6). The overall positive rates for at least one respiratory microorganism in Periods Ⅰ and Ⅱ were 23.1% (1,199/5,193) and 4.9% (1,070/21,998), respectively (p < 0.001). The overall positive rates in male and female patients were significantly different (8.7% vs. 7.9%; p = 0.016). On the FilmArray™ RP assay, positive rates in all age groups decreased significantly in Period Ⅱ compared with Period Ⅰ. AdV, Rhino/Entero, and Flu A were detected in all four seasons, but HMPV and HPIV3 were not detected. The overall positive rates on FilmArray and the Flu antigen test in Period Ⅱ were significantly decreased. In the COVID-19 test, the positive rates were high in March and April 2020, and decreased thereafter, but these increased again in the winter of 2020/2021. CONCLUSIONS: Life changes due to COVID-19 pandemic have had a significant impact on the distribution of respiratory microorganisms; our study results might provide useful information on respiratory virus epidemiology.

Serological evaluation of patients with coronavirus disease-2019 in Daegu, South Korea.

BACKGROUND: Early and accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to prevent spread of the infection. Understanding of the antibody response to SARS-CoV-2 in patients with coronavirus disease 2019 (COVID-19) is insufficient, particularly in relation to those whose responses persist for more than 1 month after the onset of symptoms. We conducted a SARS-CoV-2 antibody test to identify factors affecting the serological response and to evaluate its diagnostic utility in patients with COVID-19. METHODS AND FINDING: We collected 1,048 residual serum samples from 396 patients with COVID-19 confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2. The samples had been used for routine admission tests in six healthcare institutions in Daegu. Antibody to SARS-CoV-2 was analyzed and the cutoff index (COI) was calculated for quantitative analysis. The patients' information was reviewed to evaluate the relationship between antibody positivity and clinical characteristics. The anti-SARS-CoV-2 antibody positivity rate was 85% and the average COI was 24·3. The positivity rate and COI increased with time elapsed since symptom onset. Anti-SARS-CoV-2 antibody persisted for at least 13 weeks after symptom onset at a high COI. There was a significant difference in anti-SARS-CoV-2 antibody positivity rate between patients with and without symptoms, but not according to sex or disease course. The descending COI pattern at weeks 1 to 5 after symptom onset was significantly more frequent in patients who died than in those who recovered. CONCLUSIONS: Anti-SARS-CoV-2 antibody persisted for at least 13 weeks at a high COI in patients with COVID-19. A decreasing COI pattern up to fifth week may be associated with a poor prognosis of COVID-19. As new treatments and vaccines are introduced, it is important to monitor continuously the usefulness of anti-SARS-CoV-2 antibody assays.

Severe Acute Respiratory Syndrome Coronavirus-2 Antibody Responses in Hospitalized Patients with Coronavirus Disease 2019 in Daegu, Korea.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) started to spread in Daegu beginning at the end of February 2020. IgG and IgM antibodies against SARS-CoV-2 were measured in hospitalized patients with COVID-19 with moderate to severe symptoms to improve the understanding of antibody responses. METHODS: We enrolled 312 patients with COVID-19 admitted to seven hospitals located in Daegu. Using serum (or plasma) samples from patients with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infections, both IgG and IgM antibodies were measured using commercial enzyme-linked immunosorbent assay (R-FIND CO¬VID-19 ELISA, SG medical, Seoul, Korea). RESULTS: The median value from the initial diagnosis, confirmed by SARS-CoV-2 PCR, to the sampling date was 24 days (day 1 to 88). The total positive rate of IgG was 93.9% and the positive IgM rate was 39.4%, without considering the elapsed period after diagnosis. Positive IgG and IgM rates were highest at 100.0% and 59.0%, respectively, at 3 weeks (15 - 21 days). IgG showed a high positive rate of 79.3% even within 7 days after the initial diag-nosis of the disease and maintained a positive rate of 97.8% until after 8 weeks. CONCLUSIONS: Among hospitalized patients with COVID-19, IgG was detected from the beginning of the diagnosis and persisted for an extended time period.

Age-Related Variation of Syndecan-1 Levels in Saliva and Plasma of Healthy Individuals.

BACKGROUND: Saliva contains various cells, proteins, and molecules, and it is emerging as a material for diagnosing various diseases. Syndecan-1 (SDC-1) is a member of cell surface heparan sulfate proteoglycans and is mainly expressed in epithelial cells and plasma cells. SDC-1 is known to be associated with various cancers and inflammatory response, but there are few studies related to the change of SDC-1 levels in the saliva and plasma of healthy individuals due to aging process. METHODS: The study was conducted on 61 females who were healthy without any metabolic diseases, systemic infection, and oral cavity lesions. The subjects were divided into two groups based on age. Those below 40 years were placed in Group I and those who were 40 years and above were placed in Group II. Saliva was collected according to the guideline and the salivary flow rate (SFR) was determined. SDC-1 levels in the plasma and saliva were measured using a commercially available sandwich ELISA method. RESULTS: Age was significantly different between Group I and II (28.0 ± 2.5 vs. 47.4 ± 5.5, p < 0.001). SFR also showed a significant difference between Group I and II [0.32 (0.13 - 0.39) vs. 0.25 (0.16 - 0.35) ng/mL, p = 0.003]. Salivary SDC-1 level in Group I was significantly higher than that in Group II (p < 0.001). In addition, plasma SDC-1 level in Group I was also higher than that in Group II (p < 0.001). SFR was not significantly correlated as age increased, but it showed a significant negative correlation with salivary SDC-1 (r = -0.607, p < 0.001) and plasma SDC-1 levels (r = -0.373, p = 0.003). Salivary SDC-1 level was significantly correlated with plasma SDC-1 level (r = 0.331, p = 0.012). CONCLUSIONS: In the younger group, the SFR, salivary, and plasma SDC-1 levels were significantly higher than in the older group. Salivary and plasma SDC-1 showed significant negative correlation as age increased. Although this study was not conducted on a large scale, it might be thought to provide information on the age-related variation for salivary and plasma SDC-1 levels in the aging process.

Clinical impact of cell-free serum Epstein-Barr virus status in patients with newly diagnosed malignant lymphoma.

BACKGROUND: We analyzed cell-free serum Epstein‒Barr virus (EBV) DNA to identify its prognostic role in patients with newly diagnosed lymphoma. METHODS: We retrospectively reviewed patients diagnosed with lymphoma between January 2014 and July 2020. Patients were enrolled according to the following criteria: i) pathologically confirmed lymphomas according to the World Health Organization criteria, ii) age over 18 years, iii) serum EBV DNA measurement using polymerase chain reaction prior to first-line therapy, and iv) receipt of curative standard chemotherapy. In total, 263 patients met these criteria and were included in this study. RESULTS: Serum EBV DNA was detected in 79 patients (30.0%). Patients with positive serum EBV tended to be older (P =0.090), and the proportion of T-cell lineage lymphomas was higher than that of B-cell lymphomas (P =0.003). EBV positivity was significantly associated with more advanced disease based on the Ann Arbor staging system (P =0.008) and the International Prognostic Index (P =0.009). EBV positivity was also associated with higher disease relapse (P =0.038) and death rates (P =0.005). EBV-positive lymphomas further showed inferior long-term survival outcomes in terms of progression-free survival (PFS) (P=0.053) and overall survival (OS) (P=0.014). In the subgroup analyses, serum EBV positivity was a significant prognostic factor for patients with B-cell lineage lymphomas in terms of PFS (P =0.003) and OS (P=0.033). CONCLUSION: We demonstrated that cell-free serum EBV DNA status at the time of diagnosis has potential as a prognostic biomarker for patients with newly diagnosed malignant lymphomas.

Characterization of the novel DQA1*01:01:09 allele by next-generation sequencing.

HLA-DQA1*01:01:09 differs from HLA-DQA1*01:01:01:01 by one nucleotide substitution in codon-12 in exon 1.

How to keep patients and staff safe from accidental SARS-CoV-2 exposure in the emergency room: Lessons from South Korea's explosive COVID-19 outbreak.

OBJECTIVES: We report our experience with an emergency room (ER) shutdown related to an accidental exposure to a patient with coronavirus disease 2019 (COVID-19) who had not been isolated. SETTING: A 635-bed, tertiary-care hospital in Daegu, South Korea. METHODS: To prevent nosocomial transmission of the disease, we subsequently isolated patients with suspected symptoms, relevant radiographic findings, or epidemiology. Severe acute respiratory coronavirus 2 (SARS-CoV-2) reverse-transcriptase polymerase chain reaction assays (RT-PCR) were performed for most patients requiring hospitalization. A universal mask policy and comprehensive use of personal protective equipment (PPE) were implemented. We analyzed effects of these interventions. RESULTS: From the pre-shutdown period (February 10-25, 2020) to the post-shutdown period (February 28 to March 16, 2020), the mean hourly turnaround time decreased from 23:31 ±6:43 hours to 9:27 ±3:41 hours (P < .001). As a result, the proportion of the patients tested increased from 5.8% (N=1,037) to 64.6% (N=690) (P < .001) and the average number of tests per day increased from 3.8±4.3 to 24.7±5.0 (P < .001). All 23 patients with COVID-19 in the post-shutdown period were isolated in the ER without any problematic accidental exposure or nosocomial transmission. After the shutdown, several metrics increased. The median duration of stay in the ER among hospitalized patients increased from 4:30 hours (interquartile range [IQR], 2:17-9:48) to 14:33 hours (IQR, 6:55-24:50) (P < .001). Rates of intensive care unit admissions increased from 1.4% to 2.9% (P = .023), and mortality increased from 0.9% to 3.0% (P = .001). CONCLUSIONS: Problematic accidental exposure and nosocomial transmission of COVID-19 can be successfully prevented through active isolation and surveillance policies and comprehensive PPE use despite longer ER stays and the presence of more severely ill patients during a severe COVID-19 outbreak.

Confirmation of COVID-19 in Out-of-Hospital Cardiac Arrest Patients and Postmortem Management in the Emergency Department during the COVID-19 Outbreak.

BACKGROUND: There is currently a lack of evidence-based postresuscitation or postmortem guidelines for patients with out-of-hospital cardiac arrest (OHCA) in the setting of an emerging infectious disease. This study aimed to develop and validate a multimodal screening tool that aids in predicting the disease confirmation in emergency situations and patients with OHCA during a coronavirus disease 2019 (COVID-19) outbreak. MATERIALS AND METHODS: We conducted a retrospective, multicenter observational study of adult patients with OHCA in Daegu, Korea. To identify the potential predictors that could be used in screening tools in the emergency department, we applied logistic regression to data collected from March 1 to March 14. The prediction performance of the screening variables was then assessed and validated on the data of patients with OHCA who were treated between February 19 and March 31, 2020. General patient characteristics and hematological findings of the COVID-19-negative and COVID-19-positive groups were compared. We also evaluated confirmation test criteria as predictors for COVID-19 positivity in patients with OHCA. RESULTS: Advanced age, body temperature, and abnormal chest X-ray (CXR) revealed significant predictive ability in the derivation cohort. Of the 184 adult patients with OHCA identified in the validation cohort, 80 patients were included in the analysis. Notably, 9 patients were positive and 71 were negative on the COVID-19 reverse transcription polymerase chain reaction test. Five patients (55.6%) in the COVID-19-positive group had a fever before OHCA, and 12 (16.9%) of the COVID-19-negative group had a fever before OHCA (P = 0.018). Eight patients (88.9%) in the COVID-19-positive group had a CXR indicating pneumonic infiltration. Of the criteria for predicting COVID-19, fever or an abnormal CXR had a sensitivity of 100% (95% confidence interval [CI]: 65.4 - 100) and a specificity of 22.5% (95% CI: 13.5 - 34.0). CONCLUSION: The screening tools that combined fever or abnormal CXR had a good discriminatory ability for COVID-19 infection in adult patients with OHCA. Therefore, during the COVID-19 outbreak period, it is recommended to suspect COVID-19 infection and perform COVID-19 test if patients present with a history of fever or show abnormal findings in postmortem CXR.