Comparison of safety and efficacy between therapeutic or intermediate versus prophylactic anticoagulation for thrombosis in COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) infections often have macrovascular or microvascular thrombosis and inflammation, which are known to be associated with a poor prognosis. Heparin has been hypothesized that administration of heparin with treatment dose rather than prophylactic dose for prevention of deep vein thrombosis in COVID-19 patients. METHODS: Studies comparing therapeutic or intermediate anticoagulation with prophylactic anticoagulation in COVID-19 patients were eligible. Mortality, thromboembolic events, and bleeding were the primary outcomes. PubMed, Embase, the Cochrane Library, and KMbase were searched up to July 2021. A meta-analysis was performed using random-effect model. Subgroup analysis was conducted according to disease severity. RESULTS: Six randomized controlled trials (RCTs) with 4,678 patients and four cohort studies with 1,080 patients were included in this review. In the RCTs, the therapeutic or intermediate anticoagulation was associated with significant reductions in the occurrence of thromboembolic events (5 studies, n=4,664; relative risk [RR], 0.72; P=0.01), and a significant increase in bleeding events (5 studies, n=4,667; RR, 1.88; P=0.004). In the moderate patients, therapeutic or intermediate anticoagulation was more beneficial than prophylactic anticoagulation in terms of thromboembolic events, but showed significantly higher bleeding events. In the severe patients, the incidence of thromboembolic and bleeding events in the therapeutic or intermediate. CONCLUSIONS: The study findings suggest that prophylactic anticoagulant treatment should be used in patients with moderate and severe COVID-19 infection groups. Further studies are needed to determine more individualized anticoagulation guidance for all COVID-19 patients.

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 efficacy and safety of interferon (Type I and Type III) therapy in patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials.

Interferon (IFN) has been highlighted in several randomized controlled trials as an attractive therapeutic candidate based plausible mode of action, suppressed response in severe COVID-19, and inhibition of SARS-CoV-2 replication. This study investigated the efficacy and safety of IFN in patients with COVID-19 according to clinical severity. Randomized controlled trials evaluating the efficacy and safety of IFN (systemic or inhaled IFN-α, -ß, and -λ) treatment in adult patients with COVID-19 were identified by systematically searching electronic databases until January 2023. Risk of bias were assessed using the Cochrane risk of bias tool, meta-analysis, and certainty of evidence grading were followed for the systematic review. We included 11 trials comprising 6,124 patients. Compared with exclusive standard care or placebo, IFN therapy did not provide significant clinical benefits for mortality at day 28 (pooled risk ratio [RR] = 0.86, 95% confidence interval [CI]: 0.62-1.18, 9 studies, low-certainty evidence) and progression to mechanical ventilation (pooled RR = 1.08, 95% CI: 0.81-1.43, 6 studies, low-certainty evidence) in patients with COVID-19. IFN therapy resulted in significantly increased hospital discharge on day 14 relative to the control arm (pooled RR = 1.29, 95% CI: 1.04-1.59). These results were inconsistent compared to other comparable outcomes such as recovery at day 14 and time to clinical improvement. The IFN-treated arm was as safe as the control arm, regardless of clinical severity (pooled RR = 0.87, 95% CI: 0.64-1.19, 9 studies, low-certainty evidence). In conclusion, IFN therapy was safe but did not demonstrate favorable outcomes for major clinical indices in patients with COVID-19, particularly those with higher than moderate severity. IFN therapy was not associated with worsening outcomes in patients with severe COVID-19. Future clinical trials should evaluate the clinical efficacy of IFN therapy in patients with mild COVID-19 or at an earlier stage. Trial registration: The protocol for this review was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42022301413.

Efficacy and safety of prone position in COVID-19 patients with respiratory failure: a systematic review and meta-analysis.

BACKGROUND: Prone position has already been demonstrated to improve survival in non-COVID acute respiratory distress syndrome and has been widely performed in COVID-19 patients with respiratory failure, both in non-intubated and intubated patients. However, the beneficial effect of the prone position in COVID-19 pneumonia still remains controversial. Therefore, we aimed to evaluate the effectiveness and safety of the prone position compared with the non-prone in non-intubated and intubated COVID-19 patients, respectively. METHODS: We searched the MEDLINE, EMBASE, and Cochrane databases, as well as one Korean domestic database, on July 9, 2021, and updated the search 9 times to September 14, 2022. Studies that compared prone and non-prone positions in patients with COVID-19 were eligible for inclusion. The primary outcomes were mortality, need for intubation, and adverse events. RESULTS: Of the 1259 records identified, 9 randomized controlled trials (RCTs) and 23 nonrandomized studies (NRSs) were eligible. In the non-intubated patients, the prone position reduced the intubation rate compared with the non-prone position in 6 RCTs (n = 2156, RR 0.81, P = 0.0002) and in 18 NRSs (n = 3374, RR 0.65, P = 0.002). In the subgroup analysis according to the oxygen delivery method, the results were constant only in the HFNC or NIV subgroup. For mortality, RCTs reported no difference between prone and non-prone groups, but in NRSs, the prone position had a significant advantage in mortality [18 NRSs, n = 3361, relative risk (RR) 0.56, P < 0.00001] regardless of the oxygen delivery methods shown in the subgroup analysis. There was no RCT for intubated patients, and mortality did not differ between the prone and non-prone groups in NRSs. Adverse events reported in both the non-intubated and intubated groups were mild and similar between the prone and non-intubated groups. CONCLUSION: For non-intubated patients with COVID-19, prone positioning reduced the risk of intubation, particularly in patients requiring a high-flow oxygen system. However, the survival benefit was unclear between the prone and non-prone groups. There was insufficient evidence to support the beneficial effects of prone positioning in intubated patients. Trial registration This study was registered in the Prospective Register of Systematic Reviews on February 16, 2022 (Registration No.: CRD42022311150 ).

Early intubation and clinical outcomes in patients with severe COVID-19: a systematic review and meta-analysis.

BACKGROUND: Evidence regarding the timing of the application of mechanical ventilation among patients with severe coronavirus disease (COVID-19) is insufficient. This systematic review and meta-analysis aimed to evaluate the effectiveness of early intubation compared to late intubation in patients with severe and critical COVID-19. METHODS: For this study, we searched the MEDLINE, EMBASE, and Cochrane databases as well as one Korean domestic database on July 15, 2021. We updated the search monthly from September 10, 2021 to February 10, 2022. Studies that compared early intubation with late intubation in patients with severe COVID-19 were eligible for inclusion. Relative risk (RR) and mean difference (MD) were calculated as measures of effect using the random-effects model for the pooled estimates of in-hospital mortality, intensive care unit (ICU) length of stay (LOS), duration of mechanical ventilation (MV), hospital LOS, ICU-free days, and ventilator-free days. Subgroup analysis was performed based on the definition of early intubation and the index time. To assess the risk of bias in the included studies, we used the Risk of Bias Assessment tool for Non-randomized studies 2.0. RESULTS: Of the 1523 records identified, 12 cohort studies, involving 2843 patients with severe COVID-19 were eligible. There were no differences in in-hospital mortality (8 studies, n = 795; RR 0.91, 95% CI 0.75-1.10, P = 0.32, I2 = 33%), LOS in the ICU (9 studies, n = 978; MD -1.77 days, 95% CI -4.61 to 1.07 days, P = 0.22, I2 = 78%), MV duration (9 studies, n = 1,066; MD -0.03 day, 95% CI -1.79 to 1.72 days, P = 0.97, I2 = 49%), ICU-free days (1 study, n = 32; 0 day vs. 0 day; P = 0.39), and ventilator-free days (4 studies, n = 344; MD 0.94 day, 95% CI -4.56 to 6.43 days, P = 0.74, I2 = 54%) between the early and late intubation groups. However, the early intubation group had significant advantage in terms of hospital LOS (6 studies, n = 738; MD -4.32 days, 95% CI -7.20 to -1.44 days, P = 0.003, I2 = 45%). CONCLUSION: This study showed no significant difference in both primary and secondary outcomes between the early intubation and late intubation groups. Trial registration This study was registered in the Prospective Register of Systematic Reviews on 16 February, 2022 (registration number CRD42022311122).

Clinical Performance of Rapid and Point-of-Care Antigen Tests for SARS-CoV-2 Variants of Concern: A Living Systematic Review and Meta-Analysis.

Rapid antigen tests (RATs) for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are widely used in the Coronavirus disease 2019 (COVID-19) pandemic caused by diverse variants. Information on the real-world performance of RATs for variants is urgently needed for decision makers. Systematic searches of the available literature and updates were conducted in PubMed, Ovid-MEDLINE, Ovid-EMBASE, CENTRAL, and KMBASE for articles evaluating the accuracy of instrument-free RATs for variants up until 14 March 2022. A bivariate random effects model was utilized to calculate pooled diagnostic values in comparison with real-time reverse transcription-polymerase chain reaction as the reference test. A total of 7562 samples from six studies were available for the meta-analysis. The overall pooled sensitivity and specificity of RATs for variants were 69.7% (95% confidence interval [CI] = 62.5% to 76.1%) and 100.0% (95% CI = 98.8% to 100.0%), respectively. When an additional 2179 samples from seven studies reporting sensitivities only were assessed, the pooled sensitivity dropped to 50.0% (95% CI = 44.0% to 55.0%). These findings suggest reassessment and monitoring of the diagnostic utility of RATs for variants, especially for the sensitivity aspect, to facilitate appropriate diagnosis and management of COVID-19 patients.

Clinical efficacy and safety of interleukin-6 receptor antagonists (tocilizumab and sarilumab) in patients with COVID-19: a systematic review and meta-analysis.

This study investigated the efficacy and safety of interleukin-6 (IL-6) receptor antagonists with standard care treatment in patients with coronavirus disease 2019 (COVID-19). The randomized controlled trials were identified through systematic searches of electronic databases through February 10, 2022. In total, 17 trials comprising 8,614 patients were included. Compared with exclusive standard care or placebo, IL-6 receptor antagonists with standard of care treatment were associated with a significantly reduced all-cause mortality at 28 days (pooled risk ratios [RR], 0.88; 95% confidence interval (CI), 0.82-0.95; 17 studies) and progression to invasive mechanical ventilation (RR, 0.79; 95% CI, 0.71-0.88; nine studies). Particularly, the subgroup of patients with moderate-to-severe COVID-19 showed a significant mortality benefit (RR, 0.89; 95% CI, 0.81-0.96; four studies) and a reduced risk for mechanical ventilation (RR, 0.80; 95% CI, 0.70-0.91; three studies) with tocilizumab treatment. The frequency of serious adverse events was lower in the tocilizumab treatment group than in the standard of care treatment group (RR, 0.83; 95% CI, 0.71-0.97; 11 studies), with no significant difference in the sarilumab treatment group (RR, 1.12; 95% CI, 0.89-1.40; four studies). Our meta-analysis demonstrated that tocilizumab treatment showed promising results in reducing 28-day mortality and progression to mechanical ventilation in patients with moderate-to-severe COVID-19, without the burden of serious adverse events.Trial registration: Clinical Trials Registry India identifier: CTRI/2020/05/025369.The proper registration is PROSPERO: registration number CRD42021294120.

[Korean Clinical Imaging Guidelines for Justification of Diagnostic Imaging Study for COVID-19]. / 한국형 COVID-19 흉부영상 진단 시행 가이드라인.

To develop Korean coronavirus disease (COVID-19) chest imaging justification guidelines, eight key questions were selected and the following recommendations were made with the evidence-based clinical imaging guideline adaptation methodology. It is appropriate not to use chest imaging tests (chest radiograph or CT) for the diagnosis of COVID-19 in asymptomatic patients. If reverse transcription-polymerase chain reaction testing is not available or if results are delayed or are initially negative in the presence of symptoms suggestive of COVID-19, chest imaging tests may be considered. In addition to clinical evaluations and laboratory tests, chest imaging may be contemplated to determine hospital admission for asymptomatic or mildly symptomatic unhospitalized patients with confirmed COVID-19. In hospitalized patients with confirmed COVID-19, chest imaging may be advised to determine or modify treatment alternatives. CT angiography may be considered if hemoptysis or pulmonary embolism is clinically suspected in a patient with confirmed COVID-19. For COVID-19 patients with improved symptoms, chest imaging is not recommended to make decisions regarding hospital discharge. For patients with functional impairment after recovery from COVID-19, chest imaging may be considered to distinguish a potentially treatable disease.

Korean Association for the Study of Intestinal Diseases guidance for clinical practice of adult inflammatory bowel disease during the coronavirus disease 2019 pandemic: expert consensus statements.

Many unexpected problems have resulted from the unprecedented coronavirus disease 2019 (COVID-19) pandemic. The optimal management of patients with inflammatory bowel disease (IBD) during the COVID-19 pandemic has also been a challenge. Therefore, the Korean Association for the Study of Intestinal Diseases (KASID) developed a consensus statement of experts regarding the management of IBD during the COVID-19 pandemic. This consensus statement made recommendations regarding the risk and treatment of COVID-19 in IBD patients. This statement emphasizes that IBD is not a risk factor for COVID-19, and care should be taken not to exacerbate IBD in patients in remission state by maintaining their medications, except for corticosteroids.

SARS-CoV-2 vaccination for adult patients with inflammatory bowel disease: expert consensus statement by KASID.

Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus, is threatening global health worldwide with unprecedented contagiousness and severity. The best strategy to overcome COVID-19 is a vaccine. Various vaccines are currently being developed, and mass vaccination is in progress. Despite the very encouraging clinical trial results of these vaccines, there is insufficient information on the safety and efficacy of vaccines for inflammatory bowel disease (IBD) patients facing various issues. After reviewing current evidence and international guidelines, the Korean Association for the Study of Intestinal Diseases developed an expert consensus statement on COVID-19 vaccination issues for Korean IBD patients. This expert consensus statement emphasizes that severe acute respiratory syndrome coronavirus 2 vaccination be strongly recommended for IBD patients, and it is safe for IBD patients receiving immunomodulatory therapy.

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

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.

Development and effectiveness of a global health competency promotion program for Korean undergraduate nursing students.

AIM: This study aimed to assess the effectiveness of a programme designed to promote global health competency among nursing students. DESIGN: It used a randomized pre-post-test comparison group design to compare the effects of a global health competency programme among nursing students. METHODS: Data collection for the pre-test was carried out for 2 days (25-26 October 2018) and that of post-test was conducted for 2 days (23-24 December 2018). A total of 38 fourth-year nursing students participated in this study (14 in the international nursing group, 11 in the transcultural nursing group and 13 in the complementary and alternative medicine group). The participants were from the nursing department of a university in Cheongju. RESULTS: There were no statistically significant differences between the groups in the pre-test homogeneity test. The international nursing group showed statistically significant improvements between the pre- and post-tests in global health competency, cultural competency, global health confidence and cultural nursing confidence.

[KASID Guidance for Clinical Practice Management of Adult Inflammatory Bowel Disease during the COVID-19 Pandemic: Expert Consensus Statement].

The coronavirus disease 2019 (COVID-19) pandemic has reduced the ability to prevent or control chronic disease due to the concerns about safety in accessing health care. Inflammatory bowel disease (IBD) is a chronic condition requiring long- term sustained treatment, which is difficult in the current panedemic situation. The Korean Association for the Study of Intestinal Diseases (KASID) has developed an expert consensus statement on the clinical practice management of adult inflammatory bowel disease during the COVID-19 pandemic. This expert consensus statement is based on guidelines and clinical reports from several countries around the world. It provides recommendations to deal with the risk of COVID-19 and medication use in IBD patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and emphasizes the importance of right treatment approach to avoid worsening of the disease condition in IBD patients.

[SARS-CoV-2 Vaccination for Adult Patients with Inflammatory Bowel Disease: Expert Consensus Statements by KASID].

Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus, is threatening global health worldwide with unprecedented contagiousness and severity. The best strategy to overcome COVID-19 is a vaccine. Various vaccines are currently being developed, and mass vaccination is in progress. Despite the very encouraging clinical trial results of these vaccines, there is insufficient information on the safety and efficacy of vaccines for inflammatory bowel disease (IBD) patients facing various issues. After reviewing current evidence and international guidelines, the Korean Association for the Study of Intestinal Diseases (KASID) developed an expert consensus statement on COVID-19 vaccination issues for Korean IBD patients. This expert consensus statement emphasizes that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination be strongly recommended for IBD patients, and it is safe for IBD patients receiving immunomodulatory therapy.

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

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.

Rapid review of early status of COVID-19 infection in South Korea

Since the confirmation of the first coronavirus disease 2019 (COVID-19) patient on January 20 2020, COVID-19 infection rate ramped up between February and March in South Korea. This study aimed to provide information on the characteristics of the first two months of COVID-19 prevalence in South Korea and attempted to comprehend preliminary evidence from various sources. We used public data available from the Korea Center for Disease Control and Prevention and situation reports from the World Health Organization from February to March 2020. For additional information, health utilization data from the Organization for Economic Co-operation and Development was used for subgroup analysis. A proportion of meta-analysis was performed. We searched literatures from PubMed, KoreaMed, and CNKI (China National Knowledge Infrastructure) for identifying epidemiological characteristics of COVID-19 and treatment strategies. We monitored domestic and global disease control institutions' recommendations. The search results and reports were updated every two weeks. In South Korea, the ratio of confirmed cases is divided into two groups;before and after the occurrence of a large cluster infection explosion on February 17 2020 from a religious group called the Shincheonji Church. After the global pandemic announcement by World Health Organization on March 11 2020, the fatality rate of COVID-19 seems to be related to the number of beds and general hospitals. From the literature review, we identified a strong reproduction rate, asymptomatic period or infection, rate of exacerbation, and current treatments. The COVID-19 pandemic in South Korea was inevitable, but the early explosion of infection showed the decline curve afforded by the rigorous tracing, widespread testing, and well-organized health care system.