COVID-19 OUTCOMES IN KOREAN PATIENTS WITH GOUT

BackgroundPatients with autoimmune inflammatory rheumatic diseases are at higher risk for coronavirus disease (COVID)-19 hospitalization and worse clinical outcomes compared with the general population. However, data on the association between COVID-19 outcomes and gout, or gout-related medications are still lacking.ObjectivesWe aimed to compare COVID-19 related clinical outcomes in gout vs. non-gout patients.MethodsWe conducted a retrospective cohort study using the electronic health record-based databases of Seoul National University hospital (SNUH) from January 2021 to April 2022 mapped to a common data model. Patients with gout and without gout were matched using a large-scale propensity score (PS) algorithm. The clinical outcomes of interest were COVID-19 infection, severe COVID-19 outcomes defined as the use of mechanical ventilation, tracheostomy or extracorporeal membrane oxygenation, and death within 30 days of COVID-19 diagnosis. The hazard ratio (HR) for gout vs. non-gout patients derived by Cox proportional hazard models were estimated utilizing a 1:5 PS-matched cohort.Results2,683 patients with gout and 417,035 patients without gout were identified among the patients who visited SNUH. After 1:5 PS matching, 1,363 gout patients and 4,030 non-gout patients remained for the analysis. The risk of COVID-19 infection was not significantly different between patients with gout and those without gout (HR 1.07 [95% CI 0.59-1.84]). Within the first month after the COVID-19 diagnosis, there was also no significant difference in the risk of hospitalization (HR 0.57 [95% CI 0.03-3.90], severe COVID-19 outcomes (HR 2.90 [95% CI 0.54-13.71]), or death (HR 1.35 [95% CI 0.06-16.24]).ConclusionPatients with gout did not have an increased risk of COVID-19 infection or worse clinical outcomes. Updates of temporal trends of COVID-19 outcomes in gout patients are yet warranted as new SARS-CoV-2 variants emerge.References[1]Shin YH, et al. Autoimmune inflammatory rheumatic diseases and COVID-19 outcomes in South Korea: a nationwide cohort study. Lancet Rheumatol. 2021 Oct;3(10):e698-e706.[2]Topless RK, et al. Gout and the risk of COVID-19 diagnosis and death in the UK Biobank: a population-based study. Lancet Rheumatol. 2022 Apr;4(4):e274-e281.[3]Xie D, et al. Gout and Excess Risk of Severe SARS-CoV-2 Infection Among Vaccinated Individuals: A General Population Study. Arthritis Rheumatol.2023 Jan;75(1):122-132.Table 1.Clinical outcomes of COVID-19 infection in patients with goutOutcomesUnmatched populationPopulation with PS stratification using 10 strata1:5 PS matched populationHazard ratio (95% CI)p-valueHazard ratio (95% CI)p-valueHazard ratio (95% CI)p-valueCOVID-19 infection1.68 (1.03-2.57)0.031.20 (0.72-1.87)0.461.07 (0.59-1.84)0.82Hospitalization due to COVID-191.92 (0.32-6.05)0.391.63 (0.26-5.77)0.540.57 (0.03-3.90)0.66Severe COVID-19 infection4.72 (1.44-11.28)<0.014.22 (1.17-12.21)0.022.90 (0.54-13.71)0.20Death due to COVID-191.15 (0.07-5.18)0.900.77 (0.04-3.81)0.821.35 (0.06-16.24)0.84Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Multipurpose advanced split T7 promoter-based transcription amplification for ultrasensitive molecular diagnostics

An accurate, convenient, and rapid diagnostic platform, which can be applied in facility-limited or point-of-care (POC) settings, is essential to help prevent the spread of infectious diseases and enable the most effective treatment to be selected. In this study, we describe the development of a new isothermal molecular diagnostic system named multipurpose advanced split T7 promoter-based transcription amplification (MASTER) for the rapid and ultrasensitive detection of various pathogens containing single-stranded RNA and double-stranded DNA. MASTER produces a large number of RNA amplicons in the presence of target pathogens, which generate fluorescence or colorimetric signals based on light-up RNA aptamers or lateral flow assays. Implementing MASTER at 37 °C for<1 h achieved the detection of a single copy per reaction without cross-reactivity. Moreover, the testing of 40 clinical samples revealed that MASTER exhibited excellent accuracy with 100% sensitivity and specificity for SARS-CoV-2 diagnosis. Furthermore, a one-pot MASTER system capable of accelerating practical applications was demonstrated, indicating that the MASTER system is a promising platform for the effective surveillance of various pathogens. © 2023 Elsevier B.V.

Relational analysis between economic activities and mobility during the COVID

Coronavirus disease (COVID-19) has significantly affected daily lives since its declaration as a Pandemic in March 2020 by the WHO. Studies in Korea to interpret the relationship between COVID-19 and transportation show that there has been a decrease in public transportation use, and a significant decrease when a widespread infection occurs. In addition, COVID-19 has affected the commercial environment, particularly the number of people using commercial districts where the use of retail outlets decreased significantly. This study analyses the disease-vectors (spread factors) of COVID-19 in terms of transportation demand, the revitalisation of commercial districts, living populations, and socioeconomic indicators. It attempts to identify different infection factors for each district in Seoul using a causal analysis methodology PLS-SEM (Partial Least-Squares Structural Equation Modelling) such that COVID-19 can be managed continuously with the aim to provide a foundation for pre-emptive actions by adjusting or controlling specific influencing factors pertaining to infectious diseases. © 2023 ICE Publishing: All rights reserved.

Chemo- and Regioselective Construction of Functionalized Isocoumarin, Flavone, and Isoquinolinedione via a One-pot Reaction of o-Quinol Acetate and Soft Nucleophiles

A one-pot strategy for the synthesis of substituted isocoumarin, flavone, and isoquinolinedione derivatives through a switchable C-arylation/lactonization or SNAr reaction from a wide range of soft nucleophiles and o-quinol acetates has been developed. This base-mediated protocol proceeds under transition-metal-free conditions and selectively affords various heteroarenes in 13–98% yields from readily prepared or commercially available 1,3-dicarbonyl and α-EWG-substituted carbonyl compounds. The synthetic utility is further demonstrated in the synthesis of potential anti-HIV and anti-coronavirus derivatives and COX-2 inhibitors. In addition, detailed experimental and computational studies are performed to provide an intensive understanding and strong support of the reaction mechanism. © 2023 Wiley-VCH GmbH.

Navigating a crisis: do exploration and exploitation help SMEs when they respond to COVID-19 disruption?

This study investigates the validity of exploitation and exploration when small- and medium-sized enterprises (SMEs) navigate a highly uncertain time. Although balancing the two strategies has been thought to lead to improved firm performance in general, a combined approach appears to be problematic for SMEs due to a lack of feasibility. We theorise that the effectiveness may vary depending on a fit between the strategies and the environmental contingencies. In doing so, we considered two potential environmental contingencies of a crisis for SMEs: loss of demand and loss of supply. To put our theory to the test, we gathered 224 responses from business leaders and key individuals from Korean start-ups and tested the effectiveness of crisis management strategies. Our findings support the validity of both exploitation and exploration when firms face a loss of demand, but not a loss of supply. It implies that the effectiveness of exploration and exploitation is contingent upon a specific form of crisis experienced at the firm level. © KOSIME, ASIALICS, STEPI 2023.

In vitro Antiviral Activity of Remdesivir Against SARS-CoV-2 and its Variants

The outbreak of COVID-19 has become a public health emergency of international concern;thus, it is important to not only develop drugs for treating COVID-19 but also develop a method for evaluating the therapeutic effect based on the characteristics of SARS-CoV-2 and its variants. To test the antiviral activity of a drug against COVID-19, in this study, we established and compared experimental conditions, such as the treatment time and mode of action (dose) of the therapeutic substance, and a test method to evaluate its effectiveness. We optimized an assay for testing antiviral activity by plaque reduction, tissue culture infectious dose 50, and quantitative RT-PCR. These methods were applied to test the antiviral efficacy of the therapeutic against SARS-CoV-2. Antiviral activity testing using in vitro assays against SARS-CoV-2 and its variants was assessed by measuring plaque-reducing or cytopathic effects in Vero-E6 cells. The in vitro assay was validated by evaluating the antiviral activity of remdesivir. Remdesivir reduced SARS-CoV-2 titer without detectable cytotoxicity and successfully inhibited viral replication in a dose-dependent manner. Therefore, we suggest this in vitro assay as an effective method for testing the antiviral activity for a potential repurposed drug against COVID-19 or rapid screening of therapeutic candidates. Copyright © 2022 Journal of Bacteriology and Virology.

ASSOCIATIONS BETWEEN COVID-19 PERCEPTIONS AND PREVENTIVE BEHAVIORS IN DEMENTIA CAREGIVING DYADS

This study adopted a dyadic perspective to examine how the perceptions of COVID-19 (i.e., anxiousness & hopefulness) of dementia caregiving dyads are associated with their engagement in personal (e.g., washing hands, wearing mask) and social (e.g., avoiding physical contact and going restaurants/bars) preventive behaviors. Multiple cross-sectional Actor-Partner Interdependence Models (APIMs) were estimated using data from the 2020 NHATS/NSOC COVID-19 Supplements (N=1565). In the anxiousness models, participants' own feeling of anxiousness was associated with their own engagement in personal preventive behaviors (actor effects), and the perceived anxiousness of PLWD was associated with personal preventive behaviors of caregivers (partner effect). In the model on social preventive behaviors, both actor and partner effects were found on dementia caregiving dyads. No effect was found in the models on hopefulness. Our findings extend understandings of mutual influence within the caregiving dyads and demonstrate the possibility of developing interventions for caregivers to promote PLWD's health behaviors.

Generation of human tonsil epithelial organoids as an ex vivo model for SARS-CoV-2 infection

The palatine tonsils (hereinafter referred to as "tonsils") serve as a reservoir for viral infections and play roles in the immune system's first line of defense. The aims of this study were to establish tonsil epithelial cell-derived organoids and examine their feasibility as an ex vivo model for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The tonsil organoids successfully recapitulated the key characteristics of the tonsil epithelium, including cellular composition, histologic properties, and biomarker distribution. Notably, the basal layer cells of the organoids express molecules essential for SARS-CoV-2 entry, such as angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2) and furin, being susceptible to the viral infection. Changes in the gene expression profile in tonsil organoids revealed that 395 genes associated with oncostatin M signaling and lipid metabolism were highly upregulated within 72 h after SARS-CoV-2 infection. Notably, remdesivir suppressed the viral RNA copy number in organoid culture supernatants and intracellular viral protein levels in a dosedependent manner. Here, we suggest that tonsil epithelial organoids could provide a preclinical and translational research platform for investigating SARS-CoV-2 infectivity and transmissibility or for evaluating antiviral candidates.

Severe acute respiratory syndrome coronavirus 2 variants-Possibility of universal vaccine design: A review

Both novel and conventional vaccination strategies have been implemented worldwide since the onset of coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite various medical advances in the treatment and prevention of the spread of this contagious disease, it remains a major public health threat with a high mortality rate. As several lethal SARS-CoV-2 variants continue to emerge, the development of several vaccines and medicines, each with certain advantages and disadvantages, is underway. Additionally, many modalities are at various stages of research and development or clinical trials. Here, we summarize emerging SARS-CoV-2 variants, including delta, omicron, and "stealth omicron," as well as available oral drugs for COVID-19. We also discuss possible antigen candidates other than the receptor-binding domain protein for the development of a universal COVID-19 vaccine. The present review will serve as a helpful resource for future vaccine and drug development to combat COVID-19.(c) 2022 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

THE PROGNOSTIC IMPLICATIONS OF LIVER FUNCTION TEST ABNORMALITIES IN PATIENTS ADMITTED TO HOSPITAL WITH COVID-19

Background & Aims: Prior studies have indicated the presence of hepatic inflammation (as signified by elevated liver function test (LFT) values), as conferring an escalated risk toward adverse outcomes in patients admitted with COVID-19. In line with this hypothesis, we study the various thresholds of LFTs and its associated prognostic risks toward COVID- 19 related hospital deaths Method: This was a single-center retrospective study involving patients admitted with COVID-19. Univariate Cox regression analysis identified the LFT variables significantly associated with our primary endpoint, in-hospital death. Subsequently, 500 iterations of thresholds were generated for each biomarker to estimate the prognostic relationship between biomarker and endpoint. Multivariate Cox regression and event-analyses were performed for each threshold to identify the minimal cutoffs at which the prognostic relationship was significant. Event curves were drawn for each significant relationship. Results: A total of 858 patients with COVID-19 were included with a median follow-up time of 5 days from admission. From the total, 90 patients passed away during admission (10.5%). The deceased cases were more likely to be older (66.2 vs 55.3y p<0.001);however, there was no difference in gender (male: 66 vs 56.2% p=0.11). Between the cases and controls (no-death), deceased cases had higher incidence of nonalcoholic fatty liver disease (7.78 vs 2.99% p=0.042), COPD (18.9 vs 7.80% p=0.001), lung cancer (4.44 vs 0.65% p= 0.009), ICU admissions (81.1 vs 26% p<0.001), and intubation events (84.4 vs 19.5% p<0.001), however there was no difference in alcohol use (21.1 vs 30.6% p=0.083) and alcoholic liver disease (5.56 vs 2.08% p=0.097). Upon univariate Cox analysis, the following LFT parameters were associated with in-hospital death: Bilirubin (p<0.001), AST (p<0.001), ALT (p<0.001). However, alkaline phosphatase (p=0.449) was not associated with the primary endpoint. The iterations of event regression analyses using 500 sequences of LFT thresholds showed the following cutoffs to be significantly associated with in-hospital death (minimally significant values): ALT (281.71 IU/L), AST (120.94 IU/L), bilirubin (2.615 mg/ dL). On the multivariate analysis, while controlling for demographics and cardiopulmonary/ medical comorbidities, the following adjusted hazard ratios were derived for each cutoff: ALT (aHR: 6.43 95%CI 1.85-22.40), AST (aHR: 3.35 95%CI 1.84-6.11), and bilirubin (aHR: 2.77 95%CI 1.15-6.65). Conclusion: The delineated cutoffs for AST, ALT, and bilirubin levels can serve as clinical benchmarks to help determine when a COVID-19 infection poses significant risk. Given this finding, the cutoffs can be used as part of a risk assessment for patients to support early preventative therapies and medical management. (Table Presented)

A NOVEL PROGNOSTIC MODEL INCLUDING LIVER FUNCTION PARAMETERS ACCURATELY PREDICTS 30-DAY MORTALITY IN PATIENTS ADMITTED WITH COVID-19

Background and Aims: While the relationship between elevated liver enzymes and COVID- 19 related adverse events is well-established, a liver-dependent prognostic model that predicts the risk of death is helpful to accurately stratify admitted patients. In this study, we use a bootstrapping-enhanced method of regression modeling to predict COVID-19 related deaths in admitted patients. Method: This was a single-center, retrospective study. Univariate and multivariate Cox regression analyses were performed using 30-day mortality as the primary endpoint to establish associated hepatic risk factors. Regression-based prediction models were constructed using a series of modeling iterations with an escalating number of categorical terms. Model performance was evaluated using receiver operating characteristic (ROC) curves. Model accuracy was internally validated using bootstrapping-enhanced iterations. Results: 858 patients admitted to hospital with COVID-19 were included. 78 were deceased by 30 days (9.09%). Cox regression (greater than 20 variables) showed the following core variables to be significant: INR (aHR 1.26 95%CI 1.06-1.49), AST (aHR 1.00 95%CI 1.00- 1.00), age (aHR 1.05 95%CI 1.02-1.08), WBC (aHR 1.07 95%CI 1.03-1.11), lung cancer (aHR 3.38 95%CI 1.15-9.90), COPD (aHR 2.26 95%CI 1.21-4.22). Using these core variables and additional categorical terms, the following model iterations were constructed with their respective AUC;model 1 (core only): 0.82 95%CI 0.776-0.82, model 2 (core + demographics): 0.828 95%CI 0.785-0.828, model 3 (prior terms + additional biomarkers): 0.842 95%CI 0.799-0.842, model 4 (prior terms + comorbidities): 0.851 95%CI 0.809-0.851, model 5 (prior terms + life-sustaining therapies): 0.933 95%CI 0.91-0.933, model 6 (prior terms + COVID-19 medications): 0.934 95%CI 0.91-0.934. Model 1 demonstrated the following parameters at 0.91 TPR: 0.54 specificity, 0.17 PPV, 0.98 NPV. Bootstrapped iterations showed the following AUC for the respective models: model 1: 0.82 95%CI 0.765-0.882, model 2 0.828 95%CI 0.764-0.885, model 3 0.842 95%CI 0.779-0.883, model 4: 0.851 95%CI 0.808-0.914, model 5: 0.933 95%CI 0.901-0.957, model 6: 0.934 95%CI 0.901- 0.961. Conclusion: Model 1 displays high prediction performance (AUC >0.8) in both regression-based and bootstrapping-enhanced modeling iterations. Therefore, this model can be adopted for clinical use as a calculator to evaluate the risk of 30-day mortality in patients admitted with COVID-19. (Table Presented)

Polyethyleneimine based Delivery System Coated with Hyaluronate Amine for Improved pDNA Transfection Efficiency

Since the pandemic of COVID-19, active investigation to develop immunity to infectious disease by delivering nucleic acids has been proceeded. Particularly, many studies have been conducted on non-viral vector as several vital side-effects which were found on nucleic acid delivery system using viral vectors. In this study, we have developed plasmid DNA (pDNA) load-ed-hyaluronic acid derivative (HA) coated-polyethyleneimine (PEI) based polyplex for enhanced nucleic acid delivery efficiency. We have optimized the ratio of pDNA: PEI: HA by measuring size and protein transcription efficiency. The final product, polyplex-HA, was characterized through measuring size, zeta-potential and TEM image. Intracellular uptake and protein transcription efficiency were compared to commercially available transfection reagent, lipofectamine, through fluo-rescence image and flow cytometry. In conclusion, polyplex-HA presents a novel gene delivery system for efficient and stable protein transcription since it is available for delivering various genetic materials and has less immunoreactivity. © 2022, Korean Society of Industrial Engineering Chemistry. All rights reserved.

Building Restaurant Customers’ Trust Amidst Covid-19 Crisis Through Value-and Performance-based Information: Risk Perception as a Moderator

Purpose: To weather the Covid-19 crisis and remain sustainable, restaurants need the trust of their customers. This study tested the impact of value similarity and preventive measures on customer trust and examined the impact of customer trust on customer cooperation. This study investigated the moderating effect of risk perception between study constructs. Design/methodology/approach: A web-based survey was administered to U.S. restaurant customers. For the main study, among the 240 surveys obtained, 218 usable responses remained after screening. Multiple regression and hierarchical regression analyses were conducted to test the research hypotheses. Findings: The results indicated that value similarity and preventive measures were significant predictors in under-standing customer trust in restaurants during Covid-19. It also demonstrated that restaurants’ preventive measures were a stronger determinant than value similarity in predicting customer trust, which significantly influenced customer cooperation behavior. Hierarchical regression analysis revealed that risk perception moderated the relationship between preventive measures and customer trust. The effect of preventive measures on customer trust was greater for customers with a high level of risk perception than with those with a lower one. Research limitations/implications: The measurements of two antecedents of trust― value similarity and preventive measures― require further testing to confirm their validity and reliability in future research due to incomplete examination in prior hospitality studies. Originality/value: This study contributes to the existing knowledge by elucidating the strong impacts of both fac-tors, value similarity and preventive measures, which were found to be contributory factors of customer trust during the crisis. The findings have meaningful implications for restaurant managers who take actions against the Covid-19 crisis to achieve sustainable business growth. © 2021 People and Global Business Association.

Meteorological Characteristics during Periods of Greatly Reduced PM2.5 Concentrations in March 2020 in Seoul

In March 2020, the average concentration of PM2.5 in Seoul decreased by 44% compared to that in March 2019 (from 45 mu g m(-3) to 25 mu g m(-3)). In this study, the synoptic and local meteorological conditions during the period with reduced PM2.5 concentrations were analyzed. The synoptic meteorological conditions during March 2020 show a common characteristic of strong zonal flow and winds. Therefore, air circulation was active and meteorological conditions were unfavorable to long-range transboundary transport. Local meteorological conditions such as wind and turbulent motion at the surface were sensitive to PM2.5 concentrations. Our analyses indicate that the greatly reduced PM2.5 concentrations were mainly influenced by synoptic rather than local conditions. Decreased demand for heating of buildings due to warmer temperatures in March 2020, the economic slowdown following the outbreak of COVID-19, and the implementation of guidelines aimed at controlling particulate matter (PM) were other important causes of reduced PM2.5 emissions. A decrease in long-range transboundary transport contributed to the reduced PM2.5 concentrations.

Types of COVID-19 clusters and their relationship with social distancing in Seoul Metropolitan area in South Korea

BACKGROUND: Complete contact tracing of COVID-19 patients in Korea allows a unique opportunity to investigate cluster characteristics. This study aimed to investigate all the reported COVID-19 clusters in Seoul Metropolitan area from January 23 to September 24, 2020. METHODS: Publicly available COVID-19 data was collected from the Seoul Metropolitan city and Gyeonggi Province. Community clusters with >= 5 cases were characterized by size and duration and then categorized using K-means clustering, and the correlation between the types of clusters and the level of social distancing was investigated. RESULTS: A total of 134 clusters including 4,033 cases were identified. The clusters were categorized into small (Type I, II), medium (type III), and large (type IV) clusters. With the same number of daily confirmed cases, cases were composed of different types of clusters by different periods of time. Raising social distancing was related with shifting types of clusters from large to small sized clusters. CONCLUSIONS: Classification of clusters may provide opportunities to better portray the pattern of COVID-19 outbreaks and implement more effective strategies. Social distancing administered by the government may be effective in suppressing large clusters but may not be effective in controlling small and sporadic clusters.