Two Years of Experience and Methodology of Korean COVID-19 Living Clinical Practice Guideline Development.

BACKGROUND: In Korea, during the early phase of the coronavirus disease 2019 (COVID-19) pandemic, we responded to the uncertainty of treatments under various conditions, consistently playing catch up with the speed of evidence updates. Therefore, there was high demand for national-level evidence-based clinical practice guidelines for clinicians in a timely manner. We developed evidence-based and updated living recommendations for clinicians through a transparent development process and multidisciplinary expert collaboration. METHODS: The National Evidence-based Healthcare Collaborating Agency (NECA) and the Korean Academy of Medical Sciences (KAMS) collaborated to develop trustworthy Korean living guidelines. The NECA-supported methodological sections and 8 professional medical societies of the KAMS worked with clinical experts, and 31 clinicians were involved annually. We developed a total of 35 clinical questions, including medications, respiratory/critical care, pediatric care, emergency care, diagnostic tests, and radiological examinations. RESULTS: An evidence-based search for treatments began in March 2021 and monthly updates were performed. It was expanded to other areas, and the search interval was organized by a steering committee owing to priority changes. Evidence synthesis and recommendation review was performed by researchers, and living recommendations were updated within 3-4 months. CONCLUSION: We provided timely recommendations on living schemes and disseminated them to the public, policymakers and various stakeholders using webpages and social media. Although the output was successful, there were some limitations. The rigor of development issues, urgent timelines for public dissemination, education for new developers, and spread of several new COVID-19 variants have worked as barriers. Therefore, we must prepare systematic processes and funding for future pandemics.

Clinical characteristics of patients with COVID-19 vaccine-related pneumonitis: a case series and literature review.

BACKGROUND/AIMS: Pulmonary toxicities of coronavirus disease 2019 (COVID-19) vaccination are exceedingly rare. However, there are a few reported cases after mRNA vaccination, especially from Asian countries. The purpose of this study was to report the clinical characteristics of patients with COVID-19 vaccine-related pneumonitis (CV-P) and to review cases reported in the literature. METHODS: We performed a prospective, observational case series analysis. RESULTS: Eleven patients with a median age of 80 years were enrolled. Ten patients developed CV-P after BNT162b2-mRNA vaccination and one after ChAdOx1 nCoV-19 vaccination. We identified various patterns of CV-P, including transient infiltration, life-threatening acute respiratory distress syndrome, and aggravation of underlying interstitial lung disease. Most patients showed favorable outcomes with good responses to corticosteroid therapy. CONCLUSION: Identifying the mechanism of CV-P requires further investigation; however, radiological and laboratory findings in our case series support inflammatory dysregulation in the lung parenchyma after vaccination. Clinicians should consider CV-P in patients with atypical lung infiltration, no specific etiologies, and recent COVID-19 vaccination.

Amelioration of SARS-CoV-2 infection by ANO6 phospholipid scramblase inhibition.

As an enveloped virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delivers its viral genome into host cells via fusion of the viral and cell membranes. Here, we show that ANO6/TMEM16F-mediated cell surface exposure of phosphatidylserine is critical for SARS-CoV-2 entry and that ANO6-selective inhibitors are effective against SARS-CoV-2 infections. Application of the SARS-CoV-2 Spike pseudotyped virus (SARS2-PsV) evokes a cytosolic Ca2+ elevation and ANO6-dependent phosphatidylserine externalization in ACE2/TMPRSS2-positive mammalian cells. A high-throughput screening of drug-like chemical libraries identifies three different structural classes of chemicals showing ANO6 inhibitory effects. Among them, A6-001 displays the highest potency and ANO6 selectivity and it inhibits the single-round infection of SARS2-PsV in ACE2/TMPRSS2-positive HEK 293T cells. More importantly, A6-001 strongly inhibits authentic SARS-CoV-2-induced phosphatidylserine scrambling and SARS-CoV-2 viral replications in Vero, Calu-3, and primarily cultured human nasal epithelial cells. These results provide mechanistic insights into the viral entry process and offer a potential target for pharmacological intervention to protect against coronavirus disease 2019 (COVID-19).

Impact of a pharmaceutical care service for patients with rheumatoid arthritis using a customised mobile device (the PROUD trial): study protocol for a randomised controlled trial.

INTRODUCTION: Rheumatoid arthritis (RA) generally requires lifelong treatment; however, its medication complexity might affect non-adherence. Pharmacist-led telehealth services were as effective as face-to-face services and reduced potential side effects in outpatients with chronic diseases. This study aims to analyse the effect of a telepharmacy service with a customised mobile device in comparison with the usual pharmacist service on the humanistic and clinical outcomes in patients with RA. METHODS AND ANALYSIS: The study is designed as a prospective, randomised, open-label, and controlled trial to compare the humanistic and clinical outcomes of the pharmaceutical care service with monthly telecommunications and a customised mobile application (telepharmacy care group) against the usual service by community pharmacists (usual care group) in 256 patients with RA and prescribed at least one of the disease-modifying antirheumatic drugs. Participants will be recruited from a tertiary hospital in Republic of Korea with written informed consent. The primary outcome will be the changes in health-related quality of life as measured by the Korean version of the EuroQoL's five-dimensional questionnaire at 6 months compared with baseline. The secondary outcomes will be the changes in the following: scores of the Korean version of the Compliance Questionnaire-Rheumatology and medication knowledge at 3 and 6 months compared with baseline; scores of the Korean version of the Pharmacy Service Questionnaire at 6 months compared with baseline; clinical parameters such as erythrocyte sedimentation rate, C reactive protein level, and pain score at 3 and 6 months compared with baseline; frequency of acute care utilisation over 6 months. Analysis will be carried out with intent-to-treat and per-protocol principles. ETHICS AND DISSEMINATION: The study protocol was reviewed and approved by the Institutional Review Board (IRB) of Daegu Catholic University Medical Center (IRB no. CR-21-082-L, 14 July 2021). The study findings will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: KCT0006508.

Baseline use of hydroxychloroquine or immunosuppressive drugs and the risk of coronavirus disease 2019.

BACKGROUND/AIMS: The preventive role of hydroxychloroquine (HCQ) on coronavirus disease 2019 (COVID-19) remains unclear. The aim of this study was to examine the effects of HCQ and other immunosuppressive drugs on the incidence of COVID-19. METHODS: The data were collected from the South Korea National Health Insurance Sharing-COVID-19 database. All individuals who underwent nasopharyngeal and oropharyngeal swab tests for COVID-19 from January 2020 to May 2020 are included. The association between COVID-19 risk and HCQ use was examined in a propensity score-matched population. Factors associated with COVID-19 were identified using multiple logistic regression analysis. RESULTS: Total 8,070 patients with COVID-19 and 121,050 negative controls were included from the database. Among all participants, 381 were HCQ users. In a propensity score-matched population, the incidence of COVID-19 was 7.1% in HCQ users and 6.8% in non-users. The odds ratio (OR) for HCQ use was 1.05 with a 95% confidence interval (CI) of 0.58 to 1.89. Among the subpopulation of patients with rheumatoid arthritis (RA), 33 were diagnosed with COVID-19 and 478 were not. Use of HCQ, glucocorticoids, or other immunosuppressive drugs was not associated with COVID-19 risk, whereas abatacept use was. Chronic lung disease was an independent risk factor for COVID-19 diagnosis in patients with RA (adjusted OR, 6.07; 95% CI, 1.10 to 33.59). CONCLUSION: The risk of COVID-19 did not differ between HCQ users and non-users. Glucocorticoids, conventional disease-modifying antirheumatic drugs (DMARDs), and biological DMARDs other than abatacept did not increase the risk of COVID-19.

Lung transplantation for severe COVID-19-related ARDS.

BACKGROUND: Lung transplantation (LT) is the gold standard for various end-stage chronic lung diseases and could be a salvage therapeutic option in acute respiratory distress syndrome (ARDS). However, LT is uncertain in patients with coronavirus disease 2019 (COVID-19)-related ARDS who failed to recover despite optimal management including extracorporeal membrane oxygenation (ECMO). This study aims to describe the pooled experience of LT for patients with severe COVID-19-related ARDS in Korea. METHODS: A nationwide multicenter retrospective observational study was performed with consecutive LT for severe COVID-19-related ARDS in South Korea (June 2020-June 2021). Data were collected and compared with other LTs after bridging with ECMO from the Korean Organ Transplantation Registry. RESULTS: Eleven patients with COVID-19-related ARDS underwent LT. The median age was 60.0 years [interquartile range (IQR), 57.5-62.5; six males]. All patients were supported with venovenous ECMO at LT listing and received rehabilitation before LT. Patients were transplanted at a median of 49 (IQR, 32-66) days after ECMO cannulation. Primary graft dysfunction within 72 h of LT developed in two (18.2%). One patient expired 4 days after LT due to sepsis and one patient underwent retransplantation for graft failure. After a median follow-up of 322 (IQR, 299-397) days, 10 patients are alive and recovering well. Compared with other LTs after bridging with ECMO (n = 27), post-transplant outcomes were similar between the two groups. CONCLUSIONS: LT in patients with unresolving COVID-19-related ARDS were effective with reasonable short-term outcome.

Changes in respiratory virus infection trends during the COVID-19 pandemic in South Korea: the effectiveness of public health measures.

BACKGROUND/AIMS: Studies on the effectiveness of public health measures to prevent respiratory virus transmission in real-world settings are lacking. We investigated the effectiveness of universal mask use and adherence to other personal preventive measures on the changing viral respiratory infection patterns during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Data were extracted from the South Korean National Respiratory Virus Sentinel Surveillance System. During the COVID-19 pandemic, a cross-sectional survey on adherence to personal preventive measures was conducted. Additionally, the number of subway passengers was analyzed to estimate physical distancing compliance. RESULTS: During the pandemic, adherence to personal preventive measures significantly increased, particularly indoors and on public transportation. Respiratory virus trends were compared based on laboratory surveillance data of 47,675 patients with acute respiratory infections (2016 to 2020). The 2019 to 2020 influenza epidemic ended within 3 weeks, from the epidemic peak to the epidemic end, quickly ending the inf luenza season; with a 1.8- to 2.5-fold faster decline than in previous seasons. Previously, the overall respiratory virus positivity rate remained high after the influenza seasons had ended (47.7% to 69.9%). During the COVID-19 pandemic, this positive rate, 26.5%, was significantly lower than those in previous years. Hospital-based surveillance showed a decreased number of hospitalized patients with acute viral respiratory illnesses. CONCLUSION: This study suggests that high compliance to the use of personal preventive measures in public might reduce the incidence of all respiratory virus infections and its hospitalization rates, with no additional quarantine, isolation, or contact screening.

Prognostic Implication of Baseline Sarcopenia for Length of Hospital Stay and Survival in Patients With Coronavirus Disease 2019.

BACKGROUND: The impact of sarcopenia on clinical outcomes of coronavirus disease 2019 (COVID-19) is not clearly determined yet. We aimed to investigate the association between baseline sarcopenia and clinical outcomes in patients with COVID-19. METHODS: All hospitalized adult patients with COVID-19 who had baseline chest computed tomography (CT) scans at a Korean university hospital from February 2020 to May 2020 were included. The main outcome was time from hospital admission to discharge. Death was considered as a competing risk for discharge. Baseline skeletal muscle cross-sectional area at the level of the 12th thoracic vertebra was measured from chest CT scans. The lowest quartile of skeletal muscle index (skeletal muscle cross-sectional area divided by height-squared) was defined as sarcopenia. RESULTS: Of 121 patients (median age, 62 years; 44 men; 29 sarcopenic), 7 patients died and 86 patients were discharged during the 60-day follow-up. Patients with sarcopenia showed a longer time to discharge (median, 55 vs 28 days; p < .001) and a higher incidence of death (17.2% vs 2.2%; p = .004) than those without sarcopenia. Baseline sarcopenia was an independent predictor of delayed hospital discharge (adjusted hazard ratio [aHR], 0.47; 95% confidence interval [95% CI], 0.23-0.96), but was not independently associated with mortality in patients with COVID-19 (aHR, 3.80; 95% CI, 0.48-30.26). The association between baseline sarcopenia and delayed hospital discharge was consistent in subgroups stratified by age, sex, comorbidities, and severity of COVID-19. CONCLUSIONS: Baseline sarcopenia was independently associated with a prolonged hospital stay in patients with COVID-19. Sarcopenia could be a prognostic marker in COVID-19.

Collateral effects of the coronavirus disease 2019 pandemic on lung cancer diagnosis in Korea.

BACKGROUND: The COVID-19 pandemic is predicted to significantly affect patients with lung cancer, owing to its rapid progression and high mortality. Studies on lung cancer diagnosis and treatment during an epidemic are lacking. We analyzed the impact of COVID-19 on lung cancer diagnosis in Korea, where lung cancer incidence continues to rise. METHODS: The number of newly diagnosed lung cancer cases in three university-affiliated hospitals during the pandemic and their clinical features were compared with lung cancer cases diagnosed during the same period in the past 3 years. The effectiveness of measures taken by the study hospitals to prevent nosocomial transmission was reviewed. RESULTS: A total of 612 patients were diagnosed with lung cancer from February through June, 2017-2020. During the pandemic, the number of patients who sought consultation at the division of pulmonology of study hospitals dropped by 16% from the previous year. Responding to the pandemic, the involved hospitals created physically isolated triage areas for patients with acute respiratory infection symptoms. Wide-range screening and preventive measures were implemented, thus minimizing the delay in lung cancer diagnosis. No patient acquired COVID-19 due to hospital exposure. The proportion of patients with stage III-IV non-small-cell lung cancer (NSCLC) significantly increased (2020: 74.7% vs. 2017: 57.9%, 2018: 66.7%, 2019: 62.7%, p = 0.011). The number of lung cancers diagnosed during this period and the previous year remained the same. CONCLUSIONS: The proportion of patients with advanced NSCLC increased during the COVID-19 pandemic.