Replication kinetics and infectivity of SARS-CoV-2 Omicron variant sublineages recovered in the Republic of Korea

Objectives@#We analyzed the correlation between the infectivity and transmissibility of the severe acute respiratory syndrome coronavirus 2 Omicron sublineages BA.1, BA. 2, BA.4, and BA.5. @*Methods@#We assessed viral replication kinetics and infectivity at the cellular level. Nasopharyngeal and oropharyngeal specimens were obtained from patients with coronavirus disease 2019, confirmed using whole-genome sequencing to be caused by the Omicron sublineages BA.1, BA.2, BA.4, or BA.5. These specimens were used to infect Vero E6 cells, derived from monkey kidneys, for the purpose of viral isolation. Viral stocks were then passaged in Vero E6 cells at a multiplicity of infection of 0.01, and culture supernatants were harvested at 12-hour intervals for 72 hours. To evaluate viral replication kinetics, we determined the cycle threshold values of the supernatants using real-time reverse transcription polymerase chain reaction and converted these values to genome copy numbers. @*Results@#The viral load was comparable between BA.2, BA.4, and BA.5, whereas BA.1 exhibited a lower value. The peak infectious load of BA.4 was approximately 3 times lower than that of BA.2 and BA.5, while the peak load of BA.2 and BA.5 was about 7 times higher than that of BA.1. Notably, BA.1 demonstrated the lowest infectivity over the entire study period. @*Conclusion@#Our results suggest that the global BA.5 wave may have been amplified by the higher viral replication and infectivity of BA.5 compared to other Omicron sublineages. These analyses could support the rapid assessment of the impact of novel variants on case incidence.

Increased viral load in patients infected with severe acute respiratory syndrome coronavirus 2 Omicron variant in the Republic of Korea

Objectives@#Coronavirus disease 2019 (COVID-19) has been declared a global pandemic owingto the rapid spread of the causative agent, severe acute respiratory syndrome coronavirus 2.Its Delta and Omicron variants are more transmissible and pathogenic than other variants.Some debates have emerged on the mechanism of variants of concern. In the COVID-19 wave that began in December 2021, the Omicron variant, first reported in South Africa, became identifiable in most cases globally. The aim of this study was to provide data to inform effective responses to the transmission of the Omicron variant. @*Methods@#The Delta variant and the spike protein D614G mutant were compared with the Omicron variant. Viral loads from 5 days after symptom onset were compared usingepidemiological data collected at the time of diagnosis. @*Results@#The Omicron variant exhibited a higher viral load than other variants, resulting in greater transmissibility within 5 days of symptom onset. @*Conclusion@#Future research should focus on vaccine efficacy against the Omicron variant and compare trends in disease severity associated with its high viral load.

Guidelines for the Laboratory Diagnosis of Monkeypox in Korea

While the coronavirus disease 2019 pandemic is ongoing, monkeypox has been rapidly spreading in non-endemic countries since May 2022. Accurate and rapid laboratory tests are essential for identifying and controlling monkeypox. Korean Society for Laboratory Medicine and the Korea Disease Prevention and Control Agency have proposed guidelines for diagnosing monkeypox in clinical laboratories in Korea. These guidelines cover the type of tests, selection of specimens, collection of specimens, diagnostic methods, interpretation of test results, and biosafety. Molecular tests are recommended as confirmatory tests. Skin lesion specimens are recommended for testing in the symptomatic stage, and the collection of both blood and oropharyngeal swabs is recommended in the presymptomatic or prodromal stage.

Genomic Surveillance of SARS-CoV-2: Distribution of Clades in the Republic of Korea in 2020

Since a novel beta-coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019, there has been a rapid global spread of the virus. Genomic surveillance was conducted on samples isolated from infected individuals to monitor the spread of genetic variants of SARS-CoV-2 in Korea. The Korea Disease Control and Prevention Agency performed whole genome sequencing of SARS-CoV-2 in Korea for 1 year (January 2020 to January 2021). A total of 2,488 SARSCoV-2 cases were sequenced (including 648 cases from abroad). Initially, the prevalent clades of SARSCoV-2 were the S and V clades, however, by March 2020, GH clade was the most dominant. Only international travelers were identified as having G or GR clades, and since the first variant 501Y.V1 was identified (from a traveler from the United Kingdom on December 22 nd , 2020), a total of 27 variants of 501Y.V1, 501Y.V2, and 484K.V2 have been classified (as of January 25 th , 2021). The results in this study indicated that quarantining of travelers entering Korea successfully prevented dissemination of the SARS-CoV-2 variants in Korea.

Prognostic Value of Alpha-Fetoprotein in Patients Who Achieve a Complete Response to Transarterial Chemoembolization for Hepatocellular Carcinoma

Purpose@#Alpha-fetoprotein (AFP) is a prognostic marker for hepatocellular carcinoma (HCC). We investigated the prognostic value of AFP levels in patients who achieved complete response (CR) to transarterial chemoembolization (TACE) for HCC. @*Materials and Methods@#Between 2005 and 2018, 890 patients with HCC who achieved a CR to TACE were recruited. An AFP responder was defined as a patient who showed elevated levels of AFP (>10 ng/mL) during TACE, but showed normalization or a >50% reduction in AFP levels after achieving a CR. @*Results@#Among the recruited patients, 569 (63.9%) with naïve HCC and 321 (36.1%) with recurrent HCC after complete resection were treated. Before TACE, 305 (34.3%) patients had multiple tumors, 219 (24.6%) had a maximal tumor size >3 cm, and 22 (2.5%) had portal vein tumor thrombosis. The median AFP level after achieving a CR was 6.36 ng/mL. After a CR, 473 (53.1%) patients experienced recurrence, and 417 (46.9%) died [median progression-free survival (PFS) and overall survival (OS) of 16.3 and 62.8 months, respectively]. High AFP levels at CR (>20 ng/mL) were independently associated with a shorter PFS [hazard ratio (HR)=1.403] and OS (HR=1.284), together with tumor multiplicity at TACE (HR=1.518 and 1.666, respectively). AFP non-responders at CR (76.2%, n=359 of 471) showed a shorter PFS (median 10.5 months vs. 15.5 months, HR=1.375) and OS (median 41.4 months vs. 61.8 months, HR=1.424) than AFP responders (all p=0.001). @*Conclusion@#High AFP levels and AFP non-responders were independently associated with poor outcomes after TACE. AFP holds clinical implications for detailed risk stratification upon achieving a CR after TACE.

Treatment of direct oral anticoagulants in patients with liver cirrhosis and portal vein thrombosis

Although patients with cirrhosis are known to be in a state of “rebalance” in that pro- and anticoagulant factors increase the risk for both bleeding and thrombosis, the prevalence of portal vein thrombosis (PVT) in patients with cirrhosis can be up to 26%. Therefore, physicians should consider anticoagulation for the prevention and management of PVT in patients with cirrhosis who are at high risk of PVT. Vitamin K antagonist or low molecular weight heparin is suggested as the standard treatment for PVT in cirrhosis. With the advent of new direct-acting oral anticoagulants (DOACs), there is a paradigm shift of switching to DOACs for the treatment of PVT in patients with cirrhosis. However, the safety and efficacy of DOACs in the treatment of PVT was not well-known in patients with cirrhosis. Therefore, this review focused on the current knowledge about the efficacy, safety concerns, and hepatic metabolism of DOACs in patients with cirrhosis and PVT.

Treatment of direct oral anticoagulants in patients with liver cirrhosis and portal vein thrombosis

Although patients with cirrhosis are known to be in a state of “rebalance” in that pro- and anticoagulant factors increase the risk for both bleeding and thrombosis, the prevalence of portal vein thrombosis (PVT) in patients with cirrhosis can be up to 26%. Therefore, physicians should consider anticoagulation for the prevention and management of PVT in patients with cirrhosis who are at high risk of PVT. Vitamin K antagonist or low molecular weight heparin is suggested as the standard treatment for PVT in cirrhosis. With the advent of new direct-acting oral anticoagulants (DOACs), there is a paradigm shift of switching to DOACs for the treatment of PVT in patients with cirrhosis. However, the safety and efficacy of DOACs in the treatment of PVT was not well-known in patients with cirrhosis. Therefore, this review focused on the current knowledge about the efficacy, safety concerns, and hepatic metabolism of DOACs in patients with cirrhosis and PVT.

2019 Tabletop Exercise for Laboratory Diagnosis and Analyses of Unknown Disease Outbreaks by the Korea Centers for Disease Control and Prevention

Objectives@#The Korea Centers for Disease Control and Prevention has published “A Guideline for Unknown Disease Outbreaks (UDO).” The aim of this report was to introduce tabletop exercises (TTX) to prepare for UDO in the future. @*Methods@#The UDO Laboratory Analyses Task Force in Korea Centers for Disease Control and Prevention in April 2018, assigned unknown diseases into 5 syndromes, designed an algorithm for diagnosis, and made a panel list for diagnosis by exclusion. Using the guidelines and laboratory analyses for UDO, TTX were introduced. @*Results@#Since September 9th , 2018, the UDO Laboratory Analyses Task Force has been preparing TTX based on a scenario of an outbreak caused by a novel coronavirus. In December 2019, through TTX, individual missions, epidemiological investigations, sample treatments, diagnosis by exclusions, and next generation sequencing analysis were discussed, and a novel coronavirus was identified as the causal pathogen. @*Conclusion@#Guideline and laboratory analyses for UDO successfully applied in TTX. Conclusions drawn from TTX could be applied effectively in the analyses for the initial response to COVID-19, an ongoing epidemic of 2019 - 2020. Therefore, TTX should continuously be conducted for the response and preparation against UDO.

Guidelines for Laboratory Diagnosis of Coronavirus Disease 2019 (COVID-19) in Korea

The outbreak of coronavirus disease 2019 (COVID-19), which began in December 2019, is still ongoing in Korea, with >9,000 confirmed cases as of March 25, 2020. COVID-19 is a severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection, and real-time reverse transcription-PCR is currently the most reliable diagnostic method for COVID-19 around the world. Korean Society for Laboratory Medicine and the Korea Centers for Disease Prevention and Control propose guidelines for diagnosing COVID-19 in clinical laboratories in Korea. These guidelines are based on other related domestic and international guidelines, as well as expert opinions and include the selection of test subjects, selection of specimens, diagnostic methods, interpretation of test results, and biosafety.

A Case of Advanced Hepatocellular Carcinoma with Long-term Post-progression Survival under Repeated Transarterial Chemoembolization after Sorafenib Failure

Hepatocellular carcinoma is the third leading cause of cancer related mortality worldwide. Only 30% of patients are eligible for curative surgical resection at diagnosis. For patients with advanced hepatocellular carcinoma with accompanying portal vein tumor thrombosis, Sorafenib is recommended as first-line treatment. However, survival gain from sorafenib is unsatisfactory, and there is no standard therapy for patients who are intolerable or refractory to sorafenib. Here we report a case of a 52-year-old man who initially achieved partial response after sorafenib treatment, but eventually showed disease progression and was treated subsequently with transarterial chemoembolization (TACE). Multinodular recurrence occurred, but he was treated with repeated TACE, and has survived for 4 years so far.

Decreased S100B expression in chronic liver diseases

BACKGROUND/AIMS: Hepatic innervation in liver diseases is not fully understood. We here evaluated S100B expression as a marker of hepatic nerves in patients with various chronic liver diseases, topographically and semi-quantitatively. METHODS: Liver specimens were obtained from 70 subjects (three controls, and 32 chronic hepatitis B, 14 chronic hepatitis C, 14 liver cirrhosis, and seven hepatocellular carcinoma patients). The hepatic nerve density was calculated based on immunohistochemical staining of S100B protein in the portal tracts and hepatic lobules. S100B mRNA levels were semi-quantitatively assessed as the S100B/glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA ratio. RESULTS: The densities of the hepatic nerves in portal tracts of chronic liver diseases were not significantly different from those of normal controls but the hepatic nerve densities in lobular areas of liver cirrhosis were significantly decreased (p = 0.025). Compared to the control, the S100B/GAPDH mRNA ratio was significantly decreased in chronic liver diseases (p = 0.006) and most decreased in chronic hepatitis C patients (p = 0.023). In chronic liver diseases, The S100B/GAPDH mRNA ratio tended to decrease as the fibrosis score > 0 (p = 0.453) but the overall correlation between the S100B/GAPDH mRNA ratio and fibrosis score was not statistically significant (r = 0.061, p = 0.657). CONCLUSIONS: Hepatic innervation is decreased in cirrhotic regenerating nodules compared to the control group and seems to decrease in early stages of fibrosis progression. Further studies are needed to clarify the association between changes of hepatic innervation and chronic liver disease progression.

Emergence of Norovirus GII.17-associated Outbreak and Sporadic Cases in Korea from 2014 to 2015

Human norovirus are major causative agent of nonbacterial acute gastroenteritis. In general, genogroup (G) II.4 is the most prominent major genotype that circulate in human population and the environment. However, a shift in genotypic trends was observed in Korea in December 2014. In this study, we investigated the trend of norovirus genotype in detail using the database of Acute Diarrhea Laboratory Surveillance (K-EnterNet) in Korea. GII.17 has since become a major contributor to outbreaks of norovirus-related infections and sporadic cases in Korea, although the reason for this shift remain unknown.

First Report of Salmonella Serotype Tilene Infection in Korea / 대한임상미생물학회지

Salmonellosis is a common food- and water-borne disease and is also a major zoonosis. Currently, the isolation of rare Salmonella serotypes is increasing every year in Korea. Among them, the Salmonella serotype Tilene was first isolated from two people who visited a hospital located in Andong-si in 2013. Clinical symptoms were weak or non-existent. There was no clear epidemiological connection between the two cases. However, it was assumed that both were independently exposed to a single infectious agent. Perhaps due to their geographical proximity, molecular epidemiological analysis showed the same result between the isolated strains. This serotype has increasingly reported an association with hedgehogs. Recently, the importation of exotic animals, including hedgehogs, as pets has been gradually increasing. Thus, it is recommended that high-risk groups avoid contact with exotic pets.

Infection of Extended-Spectrum β-Lactamase Producing Shigella flexneri in Children Attending a Childcare Center in Korea

Shigella is a common cause of bacterial enteritis worldwide. Shigella sonnei accounts for 90% of Shigella infections and Shigella flexneri is rarely reported in Korea. Although the incidence of Shigella infection has decreased, the incidence of organisms with antibiotic resistance has gradually increased in Korea. An outbreak of extended-spectrum β-lactamase (ESBL)-producing S. sonnei in children was reported in Korea; however, ESBL-producing S. flexneri has not yet been reported. We report the first two cases of multidrug-resistant CTX-M-14-producing S. flexneri infections in Korean children.

Clinical Features and Response to UDCA Treatment of Primary Biliary Cirrhosis / 이화의대지

OBJECTIVES: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease that may progress to end stage liver cirrhosis. Benefits of ursodeoxycholic acid (UDCA) treatment has been investigated through large clinical studies. However, most of the studies were done in western countries and recent increase in prevalence of this relatively uncommon chronic liver disease draws attention in Korea. As early UDCA treatment effectively prevent the grave consequences of PBC progression, early diagnosis and lifelong management with UDCA is important. This study was designed to investigate the clinical features of PBC and response rates of UDCA treatments in Ewha Womans University Medical Center. METHODS: Clinical data of PBC patients diagnosed between 2001 and 2014 at Ewha Womans University Medical Center were analyzed retrospectively. RESULTS: A total of 35 patients with mean follow-up duration of 42 months were enrolled. At the diagnosis, 72.7% of the patients were asymptomatic, 5.7% had decompensated liver cirrhosis. The mean serum alkaline phosphate (ALP) level was 2.65 times upper limit of normal. UDCA was prescribed in 91.4% of the patients (n=32), among which 77.4% exhibited biochemical responses defined as serum ALP less than 2 upper limit of normal at 6 months (Mayo criteria). CONCLUSION: Most PBC patients were asymptomatic at the time of diagnosis and the average biochemical responses rate to UDCA treatment were ranged from 60.0% to 78.9% according to various response criteria. To elucidate the clinical features and courses of Korean PBC patients in detail, larger scale investigations and longer clinical follow up studies are warranted.

Modified Method of Multilocus Sequence Typing (MLST) for Serotyping in Salmonella Species

Multilocus sequence typing (MLST) of Salmonella is useful method for replacing serotyping using antisera but is limited by difficulties associated with in polymerase chain reaction (PCR). We optimized the PCR reaction, especially annealing temperature and extension time (94degrees C for 2 min; 40 cycles at 94degrees C for 30 sec, 56.8degrees C for 1 min, 72degrees C for 2 min; and 72degrees C for 10 min). The degradation of PCR product by thermostable nucleases was inhibited by using template DNAs treated proteinase K or purified by a commercialized preparation kit. The resulting modified MLST was used as accurate and fast typing method.

Caustic Injury of Upper Gastrointestinal Tract: 20 Year Experience at a Tertiary Referral Center / 대한소화기학회지

BACKGROUND/AIMS: Caustic ingestion can cause severe injury to upper gastrointestinal tract. There were few studies about clinical characteristics and treatments of caustic injury in Korea. We investigated the changes in clinical features of caustic injury over the past 20 years including pattern of endoscopic mucosal injury and treatment modality. METHODS: This study was a retrospective review of medical records from patients with caustic injury from September 1993 through December 2012. Patients were classified into two groups based on the year when caustic ingestion occurred: patients who visited the hospital from 1993 to 2002 (early group) and patients who visited the hospital from 2003 to 2012 (late group). RESULTS: A total 140 patients were included (early group [n=50] vs. late group [n=90]). Annual number of caustic ingestions did not show decreasing tendency over the past 20 years. Alkali ingestion increased (20.0% vs. 65.6%, p<0.001) and cases with more than grade 2b of esophageal mucosal injury decreased (41.3% vs. 20.7%, p=0.012) in late group. There were no differences between two groups in sex, age, proportion of accidental ingestion, and systemic/gastrointestinal complications. Use of gastric lavage (p<0.01) and broad spectrum antibiotics (p=0.03) decreased in late group. However, there was no difference in use of steroid between two groups. CONCLUSIONS: In this study, overall caustic ingestion did not decrease and ingestion of alkali agents increased over the past 20 years. Tighter legislation on caustic agents is required and we need to be alert to the best management of caustic injury.

A case of obstructive jaundice caused by tuberculous lymphadenitis: A literature review

Obstructive jaundice caused by tuberculous lymphadenitis is a rare manifestation of tuberculosis (TB), with 15 cases having been reported in Korea. We experienced a case of obstructive jaundice caused by pericholedochal tuberculous lymphadenitis in a 30-year-old man. The patient's initial serum total bilirubin level was 21.1 mg/dL. Abdominal computed tomography revealed narrowing of the bile duct by a conglomerated soft-tissue mass involving the main portal vein. Abrupt obstruction of the common bile duct was observed on cholangiography. Pathologic analysis of a ultrasonography-guided biopsy sample revealed chronic granulomatous inflammation, and an endoscopic examination revealed esophageal varices and active duodenal ulceration, the pathology of which was chronic noncaseating granulomatous inflammation. Hepaticojejunostomy was performed and pathologic analysis of the conglomerated soft-tissue mass revealed chronic granulomatous inflammation with caseation of the lymph nodes. Tuberculous lymphadenitis should be considered in patients presenting with obstructive jaundice in an endemic area.

The Clinical Value of 18F-Fluorodeoxyglucose Uptake on Positron Emission Tomography/Computed Tomography for Predicting Regional Lymph Node Metastasis and Non-curative Surgery in Primary Gastric Carcinoma / 대한소화기학회지

BACKGROUND/AIMS: Accurate preoperative detection of regional lymph nodes and evaluation of tumor resectability is critical to determining the most adequate therapy for gastric cancer. The aim of this study is to identify a possible link between 18F-fluorodeoxyglucose (18F-FDG) uptake on PET scan combined with CT scan (PET/CT) and predictions of lymph node metastasis and non-curative surgery. METHODS: This study included 156 gastric cancer patients who underwent preoperative 18F-FDG PET/CT and surgery. In cases with perceptible FDG uptake in the primary tumor or lymph nodes, the maximum standardized uptake value (SUVmax) was calculated. RESULTS: In multivariate analysis, non-curative surgery (OR, 11.05; 95% CI, 1.10-111.08; p=0.041), tumor size (> or =3 cm) (OR, 7.39; 95% CI, 2.41-22.70; p or =3 cm) (OR, 3.15; 95% CI, 1.16-8.58; p=0.025) and lymph node metastasis (OR, 3.36; 95% CI, 1.23-9.14; p=0.018) showed significant association with 18F-FDG uptake in lymph node. When the SUVmax of the primary gastric tumor was greater than 3.75, the sensitivity and specificity of PET/CT with regard to the diagnosis of metastatic lymph node were 73.5% and 74.5%. When the SUVmax of the primary gastric tumor was greater than 4.35 and the FDG uptake of lymph nodes was positive, non-curative surgery was predicted with a sensitivity of 58.8% and specificity of 91.6%. CONCLUSIONS: A high FDG uptake of the gastric tumor was related to histologic positive lymph nodes and non-curative surgery.

Unusual Complication of Crohn's Disease: Portal Hypertension Related with Rapid Progression of Portal Vein and Superior Mesenteric Vein Thrombosis / 대한내과학회지

Thromboembolic events are rare among systemic complications of inflammatory bowel disease; however, they are a significant cause of mortality when they occur. Several reports have considered thromboembolic events in patients with ulcerative colitis presenting with venous or arterial thromboembolism, such as cerebral thrombosis, deep vein thrombosis, pulmonary thromboembolism, portal vein thrombosis, or mesenteric vein thrombosis. However, increased coagulability related to Crohn's disease is extremely rare compared with that of ulcerative colitis. We report a case of a 42-year-old man with complicated portal hypertension that occurred due to extensive portal vein and mesenteric vein thrombosis. He had a monozygotic twin brother who was also in remission with Crohn's disease. The patient showed protein C and protein S deficiencies; however, he recovered with early anticoagulation therapy.