The effects of remdesivir on mortality and the requirement for mechanical ventilation in patients with COVID-19: a systematic review stratified by disease severity

Background/Aims@#The effectiveness of remdesivir treatment in reducing mortality and the requirement for mechanical ventilation (MV) remains uncertain, as randomized controlled trials (RCTs) have produced conflicting results. @*Methods@#We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and other data resources to find RCTs published prior to April 10, 2023. The selection of studies, assessment of risk of bias, and meta-analysis were conducted according to PRISMA guidelines. The primary outcomes were all-cause mortality and the need to initiate MV. @*Results@#A total of 5,068 articles were screened, from eight RCTs comprising 11,945 patients. The meta-analysis found that, compared to standard care or placebo, remdesivir treatment provided no significant all-cause mortality benefit (pooled risk ratio [RR], 0.93; 95% confidence interval [CI], 0.85–1.02; 8 studies; high certainty evidence), while subgroup analyses revealed a trend towards reduced mortality among patients requiring oxygen but not MV (pooled RR, 0.88; 95% CI, 0.77–1.00; 6 studies; I2 = 4%). The need to initiate MV (pooled RR, 0.74; 95% CI, 0.59–0.94; 7 studies; moderate certainty evidence) in remdesivir-treated patients was also reduced compared to controls. Remdesivir significantly increased clinical improvement and discharge and significantly reduced serious adverse events. @*Conclusions@#In this systematic review and meta-analysis of RCTs, it was found that remdesivir treatment did not show a substantial decrease in the risk of mortality. However, it was linked to a reduction in the necessity for additional ventilatory support, suggesting remdesivir could be beneficial for COVID-19 patients, particularly those who are not on MV.

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.

Use of Antibiotics Within the Last 14 Days of Life in Korean Patients:A Nationwide Study

Background@#Antimicrobial prescriptions for serious chronic or acute illness nearing its end stages raise concerns about the potential for futile use, adverse events, increased multidrugresistant organisms, and significant patient and social cost burdens. This study investigated the nationwide situation of how antibiotics are prescribed to patients during the last 14 days of life to guide future actions. @*Methods@#This nationwide multicenter retrospective cohort study was conducted at 13 hospitals in South Korea from November 1 to December 31, 2018. All decedents were included in the study. Antibiotic use during the last two weeks of their lives was investigated. @*Results@#A total of 1,201 (88.9%) patients received a median of two antimicrobial agents during the last two weeks of their lives. Carbapenems were prescribed to approximately half of the patients (44.4%) in the highest amount (301.2 days of therapy per 1,000 patient-days).Among the patients receiving antimicrobial agents, 63.6% were inappropriate and only 327 patients (27.2%) were referred by infectious disease specialists. The use of carbapenem (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.13–2.03; P = 0.006), underlying cancer (OR, 1.56; 95% CI, 1.20–2.01, P = 0.047), underlying cerebrovascular disease (OR, 1.88; 95% CI, 1.23–2.89, P = 0.004), and no microbiological testing (OR, 1.79; 95% CI, 1.15–2.73; P = 0.010) were independent predictors for inappropriate antibiotic prescribing. @*Conclusion@#A considerable number of antimicrobial agents are administered to patients with chronic or acute illnesses nearing their end-of-life, a high proportion of which are prescribed inappropriately. Consultation with an infectious disease specialist, in addition to an antimicrobial stewardship program, may be necessary to induce the optimal use of antibiotics.

Clinical significance of antinuclear antibody positivity in patients with severe coronavirus disease 2019

Background/Aims@#This study aimed to investigate the clinical characteristics and outcomes of fluorescent antinuclear antibody (FANA)-positive patients admitted for coronavirus disease 2019 (COVID‐19) and identify FANA as a prognostic factor of mortality. @*Methods@#This retrospective study was conducted at a university-affiliated hospital with 1,048 beds from September 2020 to March 2022. The participants were consecutive patients who required oxygenation through a high-flow nasal cannula, non-invasive or mechanical ventilation, or extracorporeal membrane oxygenation, and conducted the FANA test within 48 hours of admission. @*Results@#A total of 132 patients with severe COVID-19 were included in this study, of which 77 (58.3%) had FANA-positive findings (≥ 1:80). FANA-positive patients were older and had higher inflammatory markers and 28-day mortality than FANA- negative patients. In the multivariate Cox proportional hazard regression analysis, FANA-positive findings (hazard ratio [HR], 2.65; 95% confidence interval [CI], 1.04–6.74), age (per 1-year; HR, 1.05; 95% CI, 1.01–1.10), underlying pulmonary disease (HR, 3.16; 95% CI, 0.97–10.26), underlying hypertension (HR, 2.97; 95% CI, 1.28–6.87), and blood urea nitrogen > 20 mg/dL (HR, 3.72; 95% CI, 1.09–12.64) were independent predictors of 28-day mortality. Remdesivir (HR, 0.34; 95% CI, 0.15–0.74) was found to be an independent predictor that reduced mortality. @*Conclusions@#Our findings revealed an autoimmune phenomenon in patients with severe COVID-19, which provides an ancillary rationale for strategies to optimize immunosuppressive therapy. In particular, this study suggests the potential of FANA to predict the outcomes of COVID-19.

Development and Roll-Out of A Coronavirus Disease 2019 Clinical Pathway for Standardized Qualified Care in Public Hospitals in Korea / 감염과화학요법

Despite the coronavirus disease 2019 (COVID-19) vaccination roll-out, variant-related outbreaks have occurred repeatedly in Korea. Although public hospitals played a major role in COVID-19 patients’ care, difficulty incorporating evolving COVID-19 treatment guidelines called for a clinical pathway (CP). Eighteen public hospitals volunteered, and a professional review board was created. CPs were formulated containing inclusion/exclusion criteria, application flow charts, and standardized order sets. After CP roll-out, key parameters improved, such as increased patient/staff five-point satisfaction scores (0.41/0.57) and decreased hospital stays (1.78 days)/medical expenses (17.5%). The CPs were updated consistently after roll-out as new therapeutics drugs were introduced and quarantine policies changed.

Core Elements for Implementing Antimicrobial Stewardship Programs in Korean General Hospitals / 감염과화학요법

Currently, antimicrobial resistance (AMR) is a major threat to global public health. The antimicrobial stewardship program (ASP) has been proposed as an important approach to overcome this crisis. ASP supports the optimal use of antimicrobials, including appropriate dosing decisions, administration duration, and administration routes. In Korea, efforts are being made to overcome AMR using ASPs as a national policy. The current study aimed to develop core elements of ASP that could be introduced in domestic medical facilities. A Delphi survey was conducted twice to select the core elements through expert consensus.The core elements for implementing the ASP included (1) leadership commitment, (2) operating system, (3) action, (4) tracking, (5) reporting, and (6) education. To ensure these core elements are present at medical facilities, multiple departments must collaborate as teams for ASP operations. Establishing a reimbursement system and a workforce for ASPs are prerequisites for implementing ASPs. To ensure that ASP core elements are actively implemented in medical facilities, it is necessary to provide financial support for ASPs in medical facilities, nurture the healthcare workforce in performing ASPs, apply the core elements to healthcare accreditation, and provide incentives to medical facilities by quality evaluation criteria.

Korean Guidelines for Use of Antibiotics for Intra-abdominal Infections in Adults / 감염과화학요법

The guidelines are intended to provide practical information for the correct use of antibiotics for intra-abdominal infections in Korea. With the aim of realizing evidence-based treatment, these guidelines for the use of antibiotics were written to help clinicians find answers to key clinical questions that arise in the course of patient care, using the latest research results based on systematic literature review. The guidelines were prepared in consideration of the data on the causative pathogens of intra-abdominal infections in Korea, the antibiotic susceptibility of the causative pathogens, and the antibiotics available in Korea.

Korean Society of Infectious Diseases/National Evidence-based Healthcare Collaborating Agency Recommendations for Anti-SARSCoV-2 Monoclonal Antibody Treatment of Patients with COVID-19 / 감염과화학요법

Neutralizing antibodies targeted at the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have been developed and now under evaluation in clinical trials. The US Food and Drug Administration currently issued emergency use authorizations for neutralizing monoclonal antibodies in non-hospitalized patients with mild to moderate coronavirus disease 2019 (COVID-19) who are at high risk for progressing to severe disease and/or hospitalization. In terms of this situation, there is an urgent need to investigate the clinical aspects and to develop strategies to deploy them effectively in clinical practice. Here we provide guidance for the use of anti-SARS-CoV-2 monoclonal antibodies for the treatment of COVID-19 based on the latest evidence.

Revised Korean Society of Infectious Diseases/National Evidence-based Healthcarea Collaborating Agency Guidelines on the Treatment of Patients with COVID-19 / 감염과화학요법

Despite the global effort to mitigate the spread, coronavirus disease 2019 (COVID-19) has become a pandemic that took more than 2 million lives. There are numerous ongoing clinical studies aiming to find treatment options and many are being published daily. Some effective treatment options, albeit of variable efficacy, have been discovered. Therefore, it is necessary to develop an evidence-based methodology, to continuously check for new evidence, and to update recommendations accordingly. Here we provide guidelines on pharmaceutical treatment for COVID-19 based on the latest evidence.

Guidelines on Implementing Antimicrobial Stewardship Programs in Korea / 감염과화학요법

These guidelines were developed as a part of the 2021 Academic R&D Service Project of the Korea Disease Control and Prevention Agency in response to requests from healthcare professionals in clinical practice for guidance on developing antimicrobial stewardship programs (ASPs). These guidelines were developed by means of a systematic literature review and a summary of recent literature, in which evidence-based intervention methods were used to address key questions about the appropriate use of antimicrobial agents and ASP expansion. These guidelines also provide evidence of the effectiveness of ASPs and describe intervention methods applicable in Korea.

Korean Society of Infectious Diseases/National Evidence-based Healthcare Collaborating Agency Recommendations for Anti-SARSCoV-2 Monoclonal Antibody Treatment of Patients with COVID-19 / 감염과화학요법

Neutralizing antibodies targeted at the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have been developed and now under evaluation in clinical trials. The US Food and Drug Administration currently issued emergency use authorizations for neutralizing monoclonal antibodies in non-hospitalized patients with mild to moderate coronavirus disease 2019 (COVID-19) who are at high risk for progressing to severe disease and/or hospitalization. In terms of this situation, there is an urgent need to investigate the clinical aspects and to develop strategies to deploy them effectively in clinical practice. Here we provide guidance for the use of anti-SARS-CoV-2 monoclonal antibodies for the treatment of COVID-19 based on the latest evidence.

Revised Korean Society of Infectious Diseases/National Evidence-based Healthcarea Collaborating Agency Guidelines on the Treatment of Patients with COVID-19 / 감염과화학요법

Despite the global effort to mitigate the spread, coronavirus disease 2019 (COVID-19) has become a pandemic that took more than 2 million lives. There are numerous ongoing clinical studies aiming to find treatment options and many are being published daily. Some effective treatment options, albeit of variable efficacy, have been discovered. Therefore, it is necessary to develop an evidence-based methodology, to continuously check for new evidence, and to update recommendations accordingly. Here we provide guidelines on pharmaceutical treatment for COVID-19 based on the latest evidence.

Guidelines on Implementing Antimicrobial Stewardship Programs in Korea / 감염과화학요법

These guidelines were developed as a part of the 2021 Academic R&D Service Project of the Korea Disease Control and Prevention Agency in response to requests from healthcare professionals in clinical practice for guidance on developing antimicrobial stewardship programs (ASPs). These guidelines were developed by means of a systematic literature review and a summary of recent literature, in which evidence-based intervention methods were used to address key questions about the appropriate use of antimicrobial agents and ASP expansion. These guidelines also provide evidence of the effectiveness of ASPs and describe intervention methods applicable in Korea.

Early Safety Monitoring of COVID-19 Vaccines in Healthcare Workers

Hospital-based surveillance for adverse events was conducted on healthcare workers after they received the first dose of coronavirus disease 2019 (COVID-19) vaccine. Among the two new platform vaccines (messenger RNA- and adenoviral vector-based vaccines), the rates of systemic adverse events were significantly higher among adenovirus-vectored vaccine recipients. Fatigue (87.6% vs. 53.8%), myalgia (80.8% vs. 50.0%), headache (72.0% vs.28.8%), and fever (≥ 38.0°C, 38.7% vs. 0%) were the most common adverse events among adenovirus-vectored vaccine recipients, but most symptoms resolved within 2 days. Both types of COVID-19 vaccines were generally safe, and serious adverse events rarely occurred.

Early Safety Monitoring of COVID-19 Vaccines in Healthcare Workers

Hospital-based surveillance for adverse events was conducted on healthcare workers after they received the first dose of coronavirus disease 2019 (COVID-19) vaccine. Among the two new platform vaccines (messenger RNA- and adenoviral vector-based vaccines), the rates of systemic adverse events were significantly higher among adenovirus-vectored vaccine recipients. Fatigue (87.6% vs. 53.8%), myalgia (80.8% vs. 50.0%), headache (72.0% vs.28.8%), and fever (≥ 38.0°C, 38.7% vs. 0%) were the most common adverse events among adenovirus-vectored vaccine recipients, but most symptoms resolved within 2 days. Both types of COVID-19 vaccines were generally safe, and serious adverse events rarely occurred.

Maternal Outcomes and Clinical Characteristics of COVID-19 in Korean Pregnant Women during the Early Period of the Pandemic

The present study aimed to compare the clinical characteristics and outcomes between pregnant women and non-pregnant women of childbearing age (20–49 years old) diagnosed with coronavirus disease 2019 (COVID-19) during the initial stage of the COVID-19 pandemic in the Republic of Korea. This nationwide observational study included the information of COVID-19 patients collected by the Korea Disease Control and Prevention Agency from January 2020 to April 2021. Among 5,647 COVID-19 patients, 2,444 (43.3%) were women of childbearing age and 19 were pregnant. None of the pregnant women died. However, 4 deaths occurred among non-pregnant women aged 20–49 years. None of the 19 pregnant women with COVID-19 were admitted to the intensive care unit: they were admitted to the general ward, and none of them required supplemental oxygen. In conclusion, none of the pregnant women with COVID-19 experienced severe infection or death, unlike non-pregnant women of childbearing age.

Interim Guidelines on Antiviral Therapy for COVID-19 / 감염과화학요법

Since the first case was reported in Wuhan, Hubei Province, China on December 12, 2019, Coronavirus disease 2019 (COVID-19) has spread widely to other countries since January 2020. As of April 16, 2020, 10635 confirmed cases have been reported, with 230 deaths in Korea. COVID-19 patients may be asymptomatic or show various clinical manifestations, including acute symptoms such as fever, fatigue, sore throat; pneumonia presenting as acute respiratory distress syndrome; and multiple organ failure. As COVID-19 has such varied clinical manifestations and case fatality rates, no standard antiviral therapy regimen has been established other than supportive therapy. In the present guideline, we aim to introduce potentially helpful antiviral and other drug therapies based on in vivo and in vitro research and clinical experiences from many countries.

Strategical Preparedness and Response Actions in the Healthcare System Against Coronavirus Disease 2019 according to Transmission Scenario in Korea / 감염과화학요법

The dynamic nature of coronavirus disease 2019 (COVID-19) pandemic requires us to be efficient and flexible in resource utilization. The strategical preparedness and response actions of the healthcare system are the key component to contain COVID-19 and to decrease its case fatality ratio. Depending on the epidemiological situation, each medical institution should systematically share the responsibility for patient screening, disposition and treatment according to clinical severity. To overcome fast-paced COVID-19 pandemic, the government should be rapidly ready and primed for action according to the specific transmission scenario.

Characteristics of Klebsiella pneumoniae Isolates from Stool Samples of Patients with Liver Abscess Caused by Hypervirulent K. pneumoniae

Comparison Between the SFTS-QS Kit and the PowerChek SFTSV Real-time PCR Kit for the Detection of Severe Fever With Thrombocytopenia Syndrome Virus

The recent increase in severe fever with thrombocytopenia syndrome (SFTS) cases has led to the development of the SFTS-QS kit (MiCoBioMed, Seongnam, Korea) for detecting the SFTS virus (SFTSV, now renamed Huaiyangshan banyangvirus). SFTS-QS is a qualitative real-time reverse transcription PCR assay based on lab-on-a-chip technology. We evaluated the performance of the SFTS-QS kit and compared it with that of the PowerChek SFTSV Real-time PCR kit (PowerChek; Kogene Biotech, Seoul, Korea). A total of 117 serum samples were simultaneously assayed using the SFTS-QS and PowerChek kits. Sanger sequencing targeting the S and M segments of SFTSV was performed as the reference method. The total turnaround time of the two kits was compared. The SFTS-QS results agreed with those of PowerChek with a kappa value of 0.92. The diagnostic sensitivity and specificity of the SFTS-QS kit were both 100% (14/14 and 103/103, respectively), whereas those of the PowerChek kit were 100% (14/14) and 98.1% (101/103), respectively. The results of SFTS-QS and PowerChek were comparable; however, the SFTS-QS kit required a shorter total turnaround time. The SFTS-QS kit produced accurate and fast results and thus could serve as a useful tool for detecting SFTSV.