Immunotherapy: OFF-THE-SHELF PARTIAL HLA MATCHING SARS-COV-2 ANTIGEN SPECIFIC T CELL THERAPY FOR SEVERE COVID-19 PATIENTS

Background & Aim: Immunological characteristics of COVID-19 show pathological hyperinflammation associated with lymphopenia and dysfunctional T cell responses. These features provide a rationale for restoring functional T cell immunity in COVID-19 patients by adoptive transfer of SARS-CoV-2 specific T cells. Methods, Results & Conclusion(s): To generate SARS-CoV-2 specific T cells, we isolated peripheral blood mononuclear cells from 7 COVID-19 recovered and 13 unexposed donors. Consequently, we stimulated cells with SARS-CoV-2 peptide mixtures covering spike, membrane and nucleocapsid proteins. Then, we culture expanded cells with IL-2 for 21 days. We assessed immunophenotypes, cytokine profiles, antigen specificity of the final cell products. Our results show that SARSCoV- 2 specific T cells could be expanded in both COVID-19 recovered and unexposed groups. Immunophenotypes were similar in both groups showing CD4+ T cell dominance, but CD8+ and CD3+CD56+ T cells were also present. Antigen specificity was determined by ELISPOT, intracellular cytokine assay, and cytotoxicity assays. One out of 14 individuals who were previously unexposed to SARS-CoV-2 failed to show antigen specificity. Moreover, ex-vivo expanded SARS-CoV-2 specific T cells mainly consisted of central and effector memory subsets with reduced alloreactivity against HLA-unmatched cells suggesting the possibility for the development of third-party partial HLA-matching products. In conclusion, our findings show that SARSCoV- 2 specific T cell can be readily expanded from both COVID-19 and unexposed individuals and can therefore be manufactured as a biopharmaceutical product to treat severe COVID-19 patients.Copyright © 2023 International Society for Cell & Gene Therapy

Risk of Microbial Transmission in Reusing Gloves after Alcohol-Based Hand Hygiene

Intro: The need for re-use of gloves as an alternative to single use was raised in times of resource shortages because during the coronavirus disease 2019 pandemic, marked increase in healthcare associated infection was reported, which might owing to shortage of personal protective equipment. we aimed to evaluate the risk of microbial transmission by comparing residual microorganism after multiple patient contact according to with or without gloves in clinical practice. Method(s): Three researchers made rounds of patients while touching the same area successively followed by alcohol-based hand rub: one with bare hands, one with single gloves, and one with double gloves. Hand imprints were obtained before and after rounds, and cultured to count colony-forming units (CFU). The number of colonies was compared between groups in a semi-quantitative manner by hand area. Finding(s): Mean CFU counts after round were 10.06 for bare hands, 31.22 for single-gloved hands, and 49.67 for double-gloved hands (p=0.084). The most commonly identified microorganism after rounding was coagulase-negative Staphylococci (77.8%, 42/54), followed by Bacillus species (62.9%, 34/54). Carbapenem-resistant Acinetobacter baumannii was confirmed from a pair of double-gloved hand specimens after the rounds. That round included a patient with the same organism with the same antibiotic susceptibility results. More microorganisms were remained after alcohol-based hand rub on gloved hands than on bare hands. Conclusion(s): From our results, the possibility of microbial transmission seems more likely in gloved hands than in bare hands even after alcohol-based hand rub. Therefore, we do not recommend the re-use of gloves after alcohol-based hand hygiene.Copyright © 2023

A Sham-Controlled Randomized Trial of Low Intensity Shockwave Therapy for Erectile Dysfunction

INTRODUCTION AND OBJECTIVE: We performed a shamcontrolled, randomized prospective trial in men with ED using an electrohydraulic shockwave device FDA cleared for connective tissue activation and improved blood flow. METHOD(S): This single-blind study was performed in men with ED naive to acoustic wave and shockwave therapy. Patients were randomized to treatment and assigned to active low intensity shockwave therapy (LiSWT) (4 Hz, 0.12 mJ/mm2) or sham treatment, 2:1. Arm 1 consisted of 3 treatments of 5000 shocks every 3 weeks. Arm 2 consisted of 5000, 3000, and 3000 shocks during weeks 1, 2, and 3, respectively, followed by an identical cycle of treatment 3 weeks later. Doppler ultrasound and grayscale imaging with a 15.4 MHz probe were performed under pharmacologic erection at weeks 20 and 32. Subjects completing sham treatment were unblinded and crossed over to the opposite arm for active treatment. Post-treatment end diastolic velocity (EDV) and peak systolic velocity (PSV) were measured, and visual grading scores were used to assess extent of hypoechoic regions in the corpora cavernosa. Data were analyzed by 2-way repeated measures ANOVA with Geisser-Greenhouse correction. Pairwise comparisons were performed to baseline used Dunnett's multiple comparison test. Missing data were imputed by "last observation carried forward". RESULT(S): Although powered for 60, recruitment was limited due to COVID and 36 subjects (22 active, 14 sham) were randomized. Sham treatments showed no significant changes in outcome measures. The number of subjects with improved visual grading scores in the proximal region was consistently higher in active LiSWT vs sham (Arm 1=88.9% vs. 11.1%;Arm 2=40.0% vs. 20.0%, respectively) with statistical significance in Arm 1 at weeks 20 (p=0.005) and 32 (p=0.001). Sham subjects rolled over to active LiSWT also had improved grayscale ratings (Arm 1=33.3% vs. 11.1%;Arm 2=40.0% vs. 20.0%). After LiSWT, greater numbers of patients had higher PSV, lower EDV, or no worsening of blood flow parameters relative to baseline. Decrease in EDV was statistically significant in active treatment Arm 2 at Week 32 (p=0.003). Mean IIEF-EF scores were nominally higher in subjects in active treatment who had improved visual grading scores vs those with no improvement. Adverse events were transient. CONCLUSION(S): Flaccid penile LiSWT appears to be safe and efficacious for treating ED based on statistically significant changes from baseline between sham and active treatments in primary outcome measures.

Pulmonary thromboendarterectomy after COVID-19 infection: USA single center experience

Background: The safety and efficacy of pulmonary thromboendarterectomy (PTE) surgery after COVID-19 infection is unknown. Objective(s): Assess the outcomes of PTE in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who had COVID-19 infection. Method(s): Retrospective, chart review of PTE cases at UCSD from March 2020 through December 2021. Result(s): 315 patients underwent PTE surgery during the analysis period;23 cases (7.3%) had previous COVID-19 infection. All were asymptomatic from COVID-19 infection at time of surgery. Mean age was 46 (range 16-75;mean 55 for non-COVID group), 13 women, 10 men, mean BMI 34.8 +/- 8.1 (mean 30.7 +/- 7.5 non-COVID). 12 patients (52.2%) were on PH targeted therapy (50.5% non-COVID). Preoperative PVR was 479.2 +/- 288.4 dynes s cm (536.6 +/- 353.7 dynes s cm non-COVID);postoperative PVR was 192.7 +/- 77.1 dynes s cm (216.6 +/- 105.6 dynes s cm non-COVID). Average circulatory arrest time was 40.3 +/- 17.9 minutes (45.3 +/- 19.7 minutes non-COVID, p=0.2), with majority of cases having Level 2 UCSD surgical classification. Average ventilator time was 1.9 days (2.2 days non-COVID, p=0.7), ICU stay 4.4 days (4.4 days non-COVID, p=1.0), length of hospitalization 10.9 days (11.6 days non-COVID, p=0.4). There was 1 case (4.3%) of airway hemorrhage, 3 cases (13.0%) of reperfusion lung injury, and 2 cases (8.7%) of post-operative respiratory infection. 10 patients (43.5%) were discharged on supplemental oxygen (60.0% for non-COVID). There were no in-hospital deaths. Compared with cases operated without COVID-19 infection over the same time period, no major differences were observed. Conclusion(s): History of COVID-19 infection did not affect outcomes of PTE surgery.

Medical bridging therapy before pulmonary endarterectomy?

Introduction: Pulmonary endarterectomy (PEA) is the recommended treatment for patients with operable chronic thromboembolic pulmonary hypertension (CTEPH). Reducing PVR pre-surgery may lower the surgical risk, but efficacy of drug treatment in operable CTEPH has not yet been proven and surgeons are concerned that dissection may be more difficult in pre-treated patients. Methodology: A randomised, double-blind, placebo controlled, multinational prospective study was performed in patients with operable CTEPH and PVR >800 dynes.sec.cm-5 at baseline (NCT03273257). Patients were randomised to Riociguat or placebo for 3 months prior to PEA. Primary endpoint was the change in PVR from baseline to before PEA. Secondary endpoints included perioperative findings and evaluation of the PEA specimen. Planned recruitment was 88 patients over 2 years. Result(s): The study was terminated early because of slow recruitment and the COVID-19 pandemic. At the time of study cessation, 14 patients were randomised (7 in each group) and 11 patients completed PEA surgery. At diagnosis, PVR was 944.0 dynes.sec.cm-5 in the Riociguat group and 1007.5 dynes.sec.cm-5 in the control group. -5 -5 The mean change in PVR prior to PEA was -28.4% for Riociguat and -6.9% for placebo (p=0.14). Completeness of surgical clearance was as expected in all patients. In the Riociguat group ease of dissection plane was rated as easier in 1, normal in 3 and more difficult in 2. In the control group, it was rated as easier in 1 and normal in 4. There were no surgical complications or post-operative deaths and no new safety signals. Conclusion(s): Due to the premature study discontinuation and the limited sample size, we are unable to determine the impact of bridging therapy on PEA outcomes.

Management of patients with advanced prostate cancer-metastatic and/or castration-resistant prostate cancer: Report of the Advanced Prostate Cancer Consensus Conference (APCCC) 2022.

BACKGROUND: Innovations in imaging and molecular characterisation together with novel treatment options have improved outcomes in advanced prostate cancer. However, we still lack high-level evidence in many areas relevant to making management decisions in daily clinical practise. The 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) addressed some questions in these areas to supplement guidelines that mostly are based on level 1 evidence. OBJECTIVE: To present the voting results of the APCCC 2022. DESIGN, SETTING, AND PARTICIPANTS: The experts voted on controversial questions where high-level evidence is mostly lacking: locally advanced prostate cancer; biochemical recurrence after local treatment; metastatic hormone-sensitive, non-metastatic, and metastatic castration-resistant prostate cancer; oligometastatic prostate cancer; and managing side effects of hormonal therapy. A panel of 105 international prostate cancer experts voted on the consensus questions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The panel voted on 198 pre-defined questions, which were developed by 117 voting and non-voting panel members prior to the conference following a modified Delphi process. A total of 116 questions on metastatic and/or castration-resistant prostate cancer are discussed in this manuscript. In 2022, the voting was done by a web-based survey because of COVID-19 restrictions. RESULTS AND LIMITATIONS: The voting reflects the expert opinion of these panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results are reported in the supplementary material. We report here on topics in metastatic, hormone-sensitive prostate cancer (mHSPC), non-metastatic, castration-resistant prostate cancer (nmCRPC), metastatic castration-resistant prostate cancer (mCRPC), and oligometastatic and oligoprogressive prostate cancer. CONCLUSIONS: These voting results in four specific areas from a panel of experts in advanced prostate cancer can help clinicians and patients navigate controversial areas of management for which high-level evidence is scant or conflicting and can help research funders and policy makers identify information gaps and consider what areas to explore further. However, diagnostic and treatment decisions always have to be individualised based on patient characteristics, including the extent and location of disease, prior treatment(s), co-morbidities, patient preferences, and treatment recommendations and should also incorporate current and emerging clinical evidence and logistic and economic factors. Enrolment in clinical trials is strongly encouraged. Importantly, APCCC 2022 once again identified important gaps where there is non-consensus and that merit evaluation in specifically designed trials. PATIENT SUMMARY: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with healthcare providers worldwide. At each APCCC, an expert panel votes on pre-defined questions that target the most clinically relevant areas of advanced prostate cancer treatment for which there are gaps in knowledge. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients and their relatives as part of shared and multidisciplinary decision-making. This report focuses on the advanced setting, covering metastatic hormone-sensitive prostate cancer and both non-metastatic and metastatic castration-resistant prostate cancer. TWITTER SUMMARY: Report of the results of APCCC 2022 for the following topics: mHSPC, nmCRPC, mCRPC, and oligometastatic prostate cancer. TAKE-HOME MESSAGE: At APCCC 2022, clinically important questions in the management of advanced prostate cancer management were identified and discussed, and experts voted on pre-defined consensus questions. The report of the results for metastatic and/or castration-resistant prostate cancer is summarised here.

National trends in suicide-related behaviors among youths between 2005-2020, including COVID-19: a Korean representative survey of one million adolescents.

OBJECTIVE: It is difficult to conclude that COVID-19 is associated with a decrease in the suicide attempts rate by comparing only a short-term period. Therefore, it is necessary to examine attempted suicide rates through a trend analysis over a longer period. This study aimed to investigate an estimated long-term trend regarding the prevalence of suicide-related behaviors among adolescents in South Korea from 2005 to 2020, including COVID-19. SUBJECTS AND METHODS: We sourced data from a national representative survey (Korea Youth Risk Behavior Survey) and analyzed one million Korean adolescents aged 13 to 18 years (n=1,057,885) from 2005 to 2020. The 16-year trends regarding the prevalence of sadness or despair and suicidal ideation and attempt and the trend changes before and during COVID-19. RESULTS: Data of 1,057,885 Korean adolescents was analyzed (weighted mean age, 15.03 years; males, 52.5%; females, 47.5%). Although the 16-year trend in the prevalence of sadness or despair and suicide ideation and attempt consistently decreased (prevalence of sadness or despair between 2005-2008, 38.0% with 95% confidence interval [CI], 37.7 to 38.4 vs. prevalence in 2020, 25.0% [24.5 to 25.6]; suicide ideation between 2005-2008, 21.9% [21.6 to 22.1] vs. prevalence in 2020, 10.7% [10.3 to 11.1]; and suicide attempt between 2005-2008, 5.0% [4.9 to 5.2] vs. prevalence in 2020, 1.9% [1.8 to 2.0]), the downward slope decreased during COVID-19 (ßdiff in sadness, 0.215 with 95% CI 0.206 to 0.224; ßdiff in suicidal ideation, 0.245 [0.234 to 0.256]; and ßdiff in suicide attempt, 0.219 [0.201 to 0.237]) compared with pre-pandemic period. CONCLUSIONS: This study found that the observed risk of suicide-related behaviors during the pandemic was higher than expected through long-term trend analysis of the prevalence of sadness/despair and suicidal ideation and attempts among South Korean adolescents. We need a profound epidemiologic study of the change in mental health due to the pandemic's impact and the establishment of prevention strategies for suicide ideation and attempt.

Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.

Clinical Characteristics of Patients with Probable Coronavirus Disease 2019-associated Pulmonary Aspergillosis at a Tertiary Care Hospital in the Republic of Korea: A Case Series

Background: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a life-threatening invasive fungal infection in critically ill patients with COVID-19. However, only a few studies have reported CAPA in the Republic of Korea. Objective: To describe clinical characteristics of CAPA in patients at a tertiary care hospital in the Republic of Korea. Methods: This retrospective, observational consecutive case series study was conducted by reviewing the electronic medical records of patients who developed CAPA at Seoul National University Hospital from January 1, 2020, to August 31, 2021. CAPA was defined by European Confederation of Medical Mycology/International Society for Human and Animal Mycology (ECMM/ISHAM) consensus criteria. Patient demographics, comorbidities, corticosteroid use, clinical presentation, treatment, and outcomes were investigated. Results: Eleven patients were diagnosed with probable CAPA according to the ECMM/ISHAM criteria. One patient had classical host factor for invasive pulmonary aspergillosis before admission. All patients received corticosteroid therapy before CAPA diagnosis. The mean total corticosteroid administered before CAPA diagnosis was 220 mg of dexamethasone equivalent dose (range, 80~572 mg), and the mean duration of steroid therapy was 15 days (range, 4~34 days). The median time from intensive care unit admission to CAPA diagnosis was 12 days (range, 5~36 days). All individuals showed aggravation on chest X-rays. Ten patients were diagnosed with positive serum galactomannan (GM), and one was diagnosed with positive GM in a bronchoalveolar lavage specimen. Of the 11 patients, 8 received voriconazole-based antifungal therapy for a median of 30.5 days. Only two patients survived after antifungal treatment. Conclusion: These cases illustrate CAPA complicated in critically ill COVID-19 patients. The challenges in diagnosis and poor outcomes of CAPA emphasize the clinical suspicion and needs for further investigation. Copyright@2022 by The Korean Society for Medical Mycology. All right reserved.

Antibiotic Prescription Trends of Patients with COVID-19: Analysis of National Health Insurance Data in Republic of Korea

Background. Although COVID-19 is a viral infection, it is known that antibiotics are often prescribed due to concerns about combined bacterial infection. Therefore, we aimed to analyze how many patients with COVID-19 received the antibiotic prescription as well as what kinds of factors contributed to it using the National Health Insurance database. Methods. We retrospectively reviewed claims data for adults 19 years of age and older hospitalized for COVID-19 from December 1, 2019 to December 31, 2020. According to severity classification of the National Institutes of Health guidelines, we calculated not only the proportion of patients receiving antibiotics but also days of treatment per 1000 patient days. In addition, we investigated the factors contributing to antibiotic use by linear regression analysis. Results. Of the 55,228 patients, 47% were male, 55% were older than 50 years of age, and most patients (89%) had no underlying diseases. The majority (84%, 46,576) were classified as having mild to moderate illness, with 11% (6,168) and 5% (2,484) having severe and critical, respectively. Antibiotics were prescribed in a total of 27% (15,081). While 74% of patients with severe illness and 88% of those with critical illness received antibiotic treatment, even 18% of mild to moderate cases were prescribed antibiotics. Fluoroquinolones were the most commonly prescribed antibiotics (8,348), followed by third generation cephalosporins (5,729) and beta-lactam/betalactamase inhibitors (3,822) as shown in Figure 1. Older age, severity of disease and underlying medical conditions contributed to overall prescription rates as well as days of antibiotic use significantly (Table 1). Conclusion. Although most of COVID-19 patients had mild to moderate illness, more than a quarter were prescribed antibiotics. Judicious use of broad-spectrum antibiotics is necessary for COVID-19 patients, considering the severity of disease and the risk of bacterial co-infection.

Cortical-blood vessel assembloids exhibit Alzheimer's disease pathologies by activating glia after SARS-CoV-2 infection

A correlation between COVID-19 and Alzheimer's disease (AD) has been proposed recently. Although the number of case reports on neuroinflammation in COVID-19 patients has increased, studies of SARSCoV- 2 neurotrophic pathology using brain organoids have restricted recapitulation of those phenotypes due to insufficiency of immune cells and absence of vasculature. To overcome these limitations, we developed fused cortical-blood vessel organoids to provide blood vessels to brain organoids and obtained the characteristics of increased expression of glial cells and blood-brain barrier-like structures in brain organoids. Furthermore, we observed AD pathologies, including Abeta plaques, which were affected by the inflammatory response from SARS-CoV-2 infection. These findings provide an advanced platform to investigate human neurotrophic diseases, including COVID-19, and suggest that neuroinflammation caused by viral infection facilitates AD pathology.

COVID-19 and drivers of excess death rate in Peru: A longitudinal ecological study.

Background: Peru has experienced unprecedented mortality and economic toll due to the COVID-19 (Coronavirus disease 2019) pandemic in 2020. We aimed to assess the association between socioeconomic factors and excess death rate, and to explore the relative contribution of these factors to the differences in excess death rate during January-December 2020. Methods: Different national secondary data sources were used to describe excess death rates and different determinants, from distal to proximal. A confounding-adjusted multilevel mixed-effects linear regression was used to assess the association between these variables and excess death rates. Their relative contributions to the differences in excess death rate between the periods with the highest and lowest excess death rates were analyzed through regression-based Oaxaca-Blinder decomposition methods. Findings: The excess death rate showed an increasing trend in all regions, with different slopes. The confounding-adjusted multilevel analysis showed that higher healthcare access was associated with lower excess death rates (difference (95%CI) -0.004 (-0.005, -0.002)), whereas COVID-19 incidence was associated with higher excess death rates (difference (95%CI) 0.052 (0.042, 0.063)). The decomposition analysis showed COVID-19 incidence (41.9%), per capita income (19.4%) and unemployment rate (14.6%) as the main risk factors, while the main protective factors included per capita health expenditure (44.7%), healthcare access (33.2%) and health insurance (12.1%). Interpretation: Our study suggests that the excess death rate during the COVID-19 pandemic in Peru may have been influenced by other factors besides COVID-19 incidence, from distal to proximal drivers, including socioeconomic determinants, factors outside and within the health sector, and susceptibility factors. Further studies at individual level are needed to corroborate our findings.

Nightingale's Legacy as a Social Reform Activist: Based on Literature Review

The purpose of the study was to re-evaluate Florence Nightingale's achievements celebrating the 200th anniversary of Nightingale's birth and to reflect on her legacy. Methods: We conducted an extensive literature review with key words in Korean and English using 9 electronic databases, related data, books, articles, websites, and secondary literature. Results: As a result of this study, the five legacy of Nightingale as a social reformer were examined. First, founding nursing in response to social needs. Second, reform of the health care system. Third, a practical social activist who promoted social change for the public good. Fourth, first adoption of health statistics. Fifth, emancipation of women. Nightingale's legacy as a social reformer has had an considerable influence on our society so far. Conclusion: Nightingale was a pioneer in nursing, but she was a social reform activist who successfully transformed the medical systems and even the whole social system based on her keen insight, religious vocation, profession vision, and personal competency. In the middle of World's chaos and uncertainty due to the COVID-19 pandemic, it seems more necessary than ever to embody the legacy of Nightingale as a social reformer, and put it into practice. © 2022 Korean Academy of Nursing Administration.

Characteristics of PM2.5 Pollution and Long-range Atmospheric Transport in Background Areas (Baengnyeong and Jeju Islands)

This study evaluated the characteristics of PM2.5 pollution and long-range atmospheric transport (LRAT) at the Baengnyeong and Jeju Air Quality Research Centers in South Korea during 2018~2020. The mean concentration of PM2.5 was constant in Baengnyeong but decreased in Jeju owing to COVID-19. The significant seasonal variations of OC, EC, and NO3- in Baengnyeong and Jeju with the highest concentrations in winter may be due to the influence of high PM2.5 episodes. Meanwhile, the concentrations of SO42- and NH4+ were constant throughout the year in Baengnyeong, resulting from regional inflow from surrounding areas. The influence of anthropogenic sources and secondary formation of PM2.5 increased in summer and decreased in autumn at both sites, which was also observed at other background sites. The dominance of NO3-, K+, and Cl- in Baengnyeong was due to the influence of combustion sources and LRAT. The source of SO42-, NH4+, V, and Ni in Jeju was identified as industrial activities with the highest contribution in summer. The secondary formation of PM2.5 with external inflow effects was dominant in Baengnyeong and Jeju. The main emission source area of PM2.5 for both Baengnyeong and Jeju was East China (Hebei, Shandong, Jangsu, and Anhui), but the chemical composition and sources of PM2.5 were different between Baengnyeong and Jeju. The result of this study can be a basis for future monitoring and modeling studies on the influence of LRAT in background areas. © 2022, Journal of Korean Society for Atmospheric Environment. All rights reserved.

Immunotherapy: OFF-THE-SHELF PARTIAL HLA MATCHING SARS-COV-2 ANTIGEN SPECIFIC T CELL THERAPY: A NEW POSSIBILITY FOR COVID- 19 TREATMENT

Background & Aim: Background. Immunological characteristics of COVID-19 show pathological hyperinflammation associated with lymphopenia and dysfunctional T cell responses. These features provide a rationale for restoring functional T cell immunity in COVID-19 patients by adoptive transfer of SARS-CoV-2 specific T cells. Methods, Results & Conclusion: Methods. To generate SARS-CoV-2 specific T cells, we isolated peripheral blood mononuclear cells from 7 COVID-19 recovered and 13 unexposed donors. Consequently, we stimulated cells with SARS-CoV-2 peptide mixtures covering spike, membrane and nucleocapsid proteins. Then, we culture expanded cells with IL-2 for 21 days. We assessed immunophenotypes, cytokine profiles, antigen specificity of the final cell products. Results. Our results show that SARS-CoV-2 specific T cells could be expanded in both COVID-19 recovered and unexposed groups. Immunophenotypes were similar in both groups showing CD4+ T cell dominance, but CD8+ and CD3+CD56+ T cells were also present. Antigen specificity was determined by ELISPOT, intracellular cytokine assay, and cytotoxicity assays. One out of 14 individuals who were previously unexposed to SARS-CoV-2 failed to show antigen specificity. Moreover, ex-vivo expanded SARS-CoV-2 specific T cells mainly consisted of central and effector memory subsets with reduced alloreactivity against HLA-unmatched cells suggesting the possibility for the development of third-party partial HLA-matching products. Conclusion. In conclusion, our findings show that SARS-CoV-2 specific T cell can be readily expanded from both COVID-19 and unexposed individuals and can therefore be manufactured as a biopharmaceutical product to treat severe COVID-19 patients.

Impacts of environmental uncertainty on firms' innovation capability and stakeholder value: Evidence from the australian courier industry

COVID-19 pandemic has drawn great attention to environmental uncertainty. The current paper attempts to conceptually develop and empirically validate a research framework that explains how the firms' environmental uncertainty influences their innovation capability and stakeholder value. Drawing on contingency theory, resource dependence theory, and stakeholder theory, this study develops a conceptual framework for the related constructs and employs a partial least squares structural equation modelling (PLS-SEM) to test the suggested framework. The empirical results validate both measurement (outer) and structural (inner) models. They indicate that environmental uncertainty is negatively associated with the innovation capability and stakeholder value while innovation capability is positively related to both internal and external stakeholder value. The results also show that internal stakeholder value positively affects external stakeholder value. Providing valuable insights into logistics and supply chain management, our study contributes to research in environmental uncertainty and innovation management based on the stakeholder theory. © 2022 World Scientific Publishing Europe Ltd.

Trends in body mass index changes among Korean adolescents between 2005-2020, including the COVID-19 pandemic period: a national representative survey of one million adolescents.

OBJECTIVE: The impact of the coronavirus disease 2019 (COVID-19) pandemic on weight gain in children and adolescents remains unknown. We aimed to identify an estimated 15-year trend in mean body mass index (BMI) changes and prevalence of obesity and overweight among Korean adolescents from 2005 to 2020, including the period of the COVID-19 pandemic. PATIENTS AND METHODS: We analyzed data taken from a nationwide survey (Korea Youth Risk Behavior Survey), between 2005 and 2020. Representative samples of one million Korean adolescents aged 13-18 years (n=1,057,885) were examined. The 15-year trends in mean BMI and proportion of obesity or overweight, and the changes due to the COVID-19 pandemic were analyzed. RESULTS: The data of 1,057,885 Korean adolescents were analyzed (mean age: 14.98 years; females, 48.4%). The estimated weighted mean BMI was 20.5 kg/m2 [95% confidence interval (CI), 20.4-20.5] from 2005 to 2008 and 21.5 kg/m2 (95% CI, 21.4-21.6) in 2020 (during the COVID-19 pandemic). Although the 15-year trend of mean BMI gradually increased, the change in mean BMI before and during the pandemic significantly lessened (ßdiff, -0.027; 95% CI, -0.028 to -0.026). The 15-year (2005-2020) trend changes in the prevalence of obesity and overweight were similar (obesity prevalence from 2005-2008, 3.2%; 95% CI, 3.1-3.3 vs. obesity prevalence in 2020, 8.6%; 95% CI, 8.2-9.0; ßdiff, -0.309; 95% CI, -0.330 to -0.288). CONCLUSIONS: The 15-year trend of overall mean BMI and obesity and overweight prevalence demonstrated a significant increase; however, its slope decreased during the pandemic. These landmark results suggest the need for the development of precise strategies to prevent pediatric obesity and overweight during the COVID-19 pandemic.

A Model-Based Strategy on COVID-19 Vaccine Roll-out in the Philippines (preprint)

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. Millions of people have fallen sick, and some have died due to this affliction that has spread across the globe. The current pandemic has disrupted normal day-to-day human life, causing a profound social and economic burden. Vaccination is an important control measure that could significantly reduce the incidence of cases and mortality if properly and efficiently distributed. In this work, an age-structured model of COVID-19 transmission, incorporating an unreported infectious compartment, is developed. Three age groups are considered, namely: young (0-19 years), adult (20-64 years), and elderly (65+ years). The transmission and reporting rates are determined for each group by utilizing the number of COVID-19 cases in the National Capital Region in the Philippines. Optimal control theory is employed to identify the best vaccine allocation to different age groups. Further, three different vaccination periods are considered to reflect phases of vaccination priority groups: the first, second, and third account for the inoculation of the elderly, adult and elderly, and all three age groups, respectively. This study could guide in making informed decisions in mitigating a population-structured disease transmission under limited resources.