Incidence and clinical outcomes of bacterial superinfections in critically ill patients with COVID-19

Background Bacterial superinfection is not uncommon in critically ill patients with coronavirus disease (COVID-19) pneumonia requiring intensive care unit (ICU) treatment. However, there is still a lack of evidence related to bacterial superinfection and their clinical significance in critically ill patients with COVID-19. Therefore, we assessed the incidence of bacterial superinfections and their effects on clinical outcomes in critically ill patients with COVID-19. Materials and methods This single-center retrospective cohort study analyzed critically ill patients with COVID-19 admitted to the ICU at a tertiary academic hospital between February 2020 and December 2021. We reviewed data including patient demographics, clinical and microbiological characteristics, and outcomes. Results During the study period, 106 patients (median [IQR] age, 67 [58–75] years) were included, of which 32 (30%) were diagnosed with bacterial superinfections. Of these, 12 cases (38%) were associated with multidrug-resistant pathogens. Klebsiella aerogenes (6 cases [19%]) and Klebsiella pneumoniae (6 cases [19%]) were the most common pathogens associated with superinfections. The median time to bacterial superinfection was 13 (IQR, 9–20) days after ICU admission. Patients with bacterial superinfections had significantly fewer ventilator-free days on day 28 (0 [IQR, 0–0] days) than those without bacterial superinfections (19 [IQR, 0–22] days) (p < 0.001). Patients with bacterial superinfections had a longer ICU length of stay (32 [IQR, 9–53] days) than those without bacterial superinfections (11 [IQR, 7–18] days) (p < 0.001). Additionally, they had a longer hospital length of stay after ICU admission (39 [IQR, 18–62] days) than those without bacterial superinfections (18 [IQR, 12–37] days) (p = 0.001). There were no differences in ICU mortality or in-hospital mortality between the two groups. In the multivariable analysis, higher SAPS II score (OR, 2.697;95% CI, 1.086–6.695) and thrombocytopenia (OR, 3.318;95% CI, 1.355–8.123) were identified as risk factors for development of bacterial superinfection. Conclusion In critically ill patients with COVID-19, bacterial superinfections were common, and more than one-third of the bacterial superinfection cases were caused by multidrug-resistant pathogens. As patients with bacterial superinfections had worse clinical outcomes, the development of bacterial superinfections should be actively monitored.

Exploring the pH dependence of the SARS‐CoV‐2 complete fusion domain and the role of its unique structural features

SARS‐CoV‐2 may enter target cells through the process of membrane fusion at either the plasma (~pH 7.4–7.0) or endosomal (~pH 6.5–5.0) membrane in order to deliver its genetic information. The fusion domain (FD) of the spike glycoprotein is responsible for initiating fusion and is thus integral to the viral life cycle. The FD of SARS‐CoV‐2 is unique in that it consists of two structurally distinctive regions referred to as the fusion peptide (FP) and the fusion loop (FL);yet the molecular mechanisms behind how this FD perturbs the membrane to initiate fusion remains unclear. In this study via solution NMR, we witnessed only a slight conformational change in the FD between pH 7.4 and pH 5.0, resulting in a minor elongation of helix 1. However, we found that the FD's ability to mediate membrane fusion has a large and significant pH dependence, with fusion events being more readily induced at low pH. Interestingly, a biphasic relationship between the environmental pH and fusogenicity was discovered, suggesting a preference for the FD to initiate fusion at the late endosomal membrane. Furthermore, the conserved disulfide bond and hydrophobic motif “LLF” were found to be critical for the function of the complete FD, with minimal activity witnessed when either was perturbed. In conclusion, these findings indicate that the SARS‐CoV‐2 FD preferably initiates fusion at a pH similar to the late endosome through a mechanism that heavily relies on the internal disulfide bond of the FL and hydrophobic LLF motif within the FP.

Effect of prone positioning on gas exchange according to lung morphology in patients with acute respiratory distress syndrome.

BACKGROUND: There are limited data on the clinical effects of prone positioning according to lung morphology. We aimed to determine whether the gas exchange response to prone positioning differs according to lung morphology. METHODS: This retrospective study included adult patients with moderate-to-severe acute respiratory distress syndrome (ARDS). The lung morphology of ARDS was assessed by chest computed tomography scan and classified as "diffuse" or "focal." The primary outcome was change in partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio after the first prone positioning session: first, using the entire cohort, and second, using subgroups of patients with diffuse ARDS matched 2 to 1 with patients with focal ARDS at baseline. RESULTS: Ninety-five patients were included (focal ARDS group, 23; diffuse ARDS group, 72). Before prone positioning, the focal ARDS group showed worse oxygenation than the diffuse ARDS group (median PaO2/FiO2 ratio, 79.9 mm Hg [interquartile range (IQR)], 67.7-112.6 vs. 104.0 mm Hg [IQR, 77.6-135.7]; P=0.042). During prone positioning, the focal ARDS group showed a greater improvement in the PaO2/FiO2 ratio than the diffuse ARDS group (median, 55.8 mm Hg [IQR, 11.1-109.2] vs. 42.8 mm Hg [IQR, 11.6-83.2]); however, the difference was not significant (P=0.705). Among the PaO2/FiO2-matched cohort, there was no significant difference in change in PaO2/FiO2 ratio after prone positioning between the groups (P=0.904). CONCLUSIONS: In patients with moderate-to-severe ARDS, changes in PaO2/FiO2 ratio after prone positioning did not differ according to lung morphology. Therefore, prone positioning can be considered as soon as indicated, regardless of ARDS lung morphology.

Equal Opportunities for Foreign Seafarers to Ensure Sustainable Development in the Korean Merchant Shipping Industry

Despite the increasing number of foreign seafarers working in the Korean shipping industry and the growing concern for psycho-emotional stress due to discrimination in the maritime sector, few studies have focused on the working environment of foreign seafarers on South Korean vessels. This study aimed to determine whether foreign seafarers perceived discrimination in the Korean shipping industry and if so, the types of discrimination they faced and how they responded to this challenge. A survey was conducted to assess foreign seafarers' experiences of discrimination, understanding of their own human rights, and level of satisfaction in working with Korean seafarers as well as identifying positive factors. The main positive findings included the kindness of colleagues, and excellent welfare facilities and benefits;whilst the most frequently reported negative factors related to language barriers and food types. These findings can be used to identify and share best practices and help determine priority areas for action. However, as the number of participants was small due to difficulties in contacting foreign seafarers during COVID-19 restrictions, further research is necessary to understand and improve the working environment of foreign seafarers on South Korean vessels.

A study on the impact of COVID-19 SMS on preventive behavior-focused on the confirmed patients notification SMS

Background/Objectives: The Republic of Korea is still a good example of k-prevention which SMS played a big role in real time. Therefore, the effect of SMS and covid 19 preventive behavior was studied. Methods/Statistical analysis: The survey respondents were focused on university students in the Chungnam region of Korea. The number of survey respondents was 135, 53 male students, 39.3%, and 82 female students, 60.7%. Looking at the distribution by grade, the fourth year was the most with 66 students and 48.9%, followed by the third year with 29 students and 21.5%, and the second year with 22 students and 16.3%. Findings: Looking at the table3 shaded areas, the CFA result of AVE.5 or less and CR.7 or less, perceived sensitivity and perceived disability, did not secure concentration validity. -As a result of CFA, the main concepts for this study were found to be inappropriate for analyzing the research model. Accordingly, analysis is performed using regression analysis rather than structural equations. The diagonal matrix for each factor in italics is the variance extraction index. The correlation between subjective norm and behavioral intention was highest (r=.703), perceived benefit (r=.655), perceived seriousness (r=.493), perceived sensitivity (r=.491) It also shows a significant relationship with the back. However, there was no significant relationship between perceived disability and behavioral intention. As a result of conducting multiple regression analysis of the concepts constituting the health belief model as an independent variable with behavioral intention as a dependent variable, self-efficacy (beta=.439, p<.001) and perceived benefit (beta=.321, p) Only <.001 appears to have a significant effect. Improvements/Applications: The SMS is helpful in preventing one's own health that the perceived benefit affects the preventive behavior. Therefore, the local governments that send the SMS is helpful in the position of the recipient.

Lassa virus glycoprotein complex review: insights into its unique fusion machinery.

Lassa virus (LASV), an arenavirus endemic to West Africa, causes Lassa fever-a lethal hemorrhagic fever. Entry of LASV into the host cell is mediated by the glycoprotein complex (GPC), which is the only protein located on the viral surface and comprises three subunits: glycoprotein 1 (GP1), glycoprotein 2 (GP2), and a stable signal peptide (SSP). The LASV GPC is a class one viral fusion protein, akin to those found in viruses such as human immunodeficiency virus (HIV), influenza, Ebola virus (EBOV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These viruses are enveloped and utilize membrane fusion to deliver their genetic material to the host cell. Like other class one fusion proteins, LASV-mediated membrane fusion occurs through an orchestrated sequence of conformational changes in its GPC. The receptor-binding subunit, GP1, first engages with a host cell receptor then undergoes a unique receptor switch upon delivery to the late endosome. The acidic pH and change in receptor result in the dissociation of GP1, exposing the fusion subunit, GP2, such that fusion can occur. These events ultimately lead to the formation of a fusion pore so that the LASV genetic material is released into the host cell. Interestingly, the mature GPC retains its SSP as a third subunit-a feature that is unique to arenaviruses. Additionally, the fusion domain contains two separate fusion peptides, instead of a standard singular fusion peptide. Here, we give a comprehensive review of the LASV GPC components and their unusual features.

Impact of COVID-19 on pregnant women in South Korea: Focusing on prevalence, severity, and clinical outcomes.

BACKGROUND: In the era of coronavirus disease 2019 (COVID-19) pandemic, there is a paucity of information regarding actual prevalence of COVID-19 in pregnant women compared to non-pregnant women. The purpose of this study was to investigate the prevalence of COVID-19 infection and clinical outcome in pregnant women and non-pregnant women. METHODS: This is a nationwide cross-sectional study in South Korea between January 2020 and February 2021 using the claim database. The primary outcome was the prevalence of COVID-19 in pregnant women, and the secondary outcome was the occurrence of severe COVID-19 illness among infected patients. Severity of COVID-19 was classified into four categories according to WHO ordinal scale. RESULTS: The prevalence of COVID-19 infection was lower in pregnant women than non-pregnant women aged 20-44 (0·02% vs. 0.14%, p < 0.0001). However, among COVID-19 positive women at age 20-44, pregnant women was at higher risk of oxygen therapy after hospitalization (score 4 in WHO ordinal scale: 6.4% vs. 1.6%, p < 0.05). There were no deaths or hospitalized severe disease in pregnant women with COVID-19, although the majority of them (96·2%) were admitted to hospital. On the other hand, 42·3% of non-pregnant women at 20-44 age were admitted to hospital and 0.04% of them died and 0.1% had hospitalized severe disease. CONCLUSIONS: The prevalence of COVID-19 infection in pregnant women was lower than non-pregnant women in Korea, resulting in relatively small cases of fatality. It has implications that public health policy, such as an effective response to COVID-19 and a powerful preemptive strategy for pregnant women, can lower risk of COVID-19 infection and better clinical outcomes in pregnant women with COVID-19.

Identifying Distinct Structural Features of the SARS-CoV-2 Spike Protein Fusion Domain Essential for Membrane Interaction.

The SARS-CoV-2 spike protein is the primary antigenic determinant of the virus and has been studied extensively, yet the process of membrane fusion remains poorly understood. The fusion domain (FD) of viral glycoproteins is well established as facilitating the initiation of membrane fusion. An improved understanding of the structural plasticity associated with these highly conserved regions aids in our knowledge of the molecular mechanisms that drive viral fusion. Within the spike protein, the FD of SARS-CoV-2 exists immediately following S2' cleavage at the N-terminus of the S2 domain. Here we have shown that following the introduction of a membrane at pH 7.4, the FD undergoes a transition from a random coil to a more structurally well-defined postfusion state. Furthermore, we have classified the domain into two distinct regions, a fusion peptide (FP, S816-G838) and a fusion loop (FL, D839-F855). The FP forms a helix-turn-helix motif upon association with a membrane, and the favorable entropy gained during this transition from a random coil is likely the driving force behind membrane insertion. Membrane depth experiments then revealed the FP is found inserted within the membrane below the lipid headgroups, while the interaction of the FL with the membrane is shallower in nature. Thus, we propose a structural model relevant to fusion at the plasma membrane in which the FP inserts itself just below the phospholipid headgroups and the FL lays upon the lipid membrane surface.

Effects of renin-angiotensin system blockers on the risk and outcomes of severe acute respiratory syndrome coronavirus 2 infection in patients with hypertension.

BACKGROUND/AIMS: There are concerns that the use of renin-angiotensin system (RAS) blockers may increase the risk of being infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or progressing to a severe clinical course after infection. This this study aimed to investigate the influence of RAS blockers on the risk and severity of SARS-CoV-2 infection. METHODS: We conducted a retrospective cohort study analyzing nationwide claims data of 215,184 adults who underwent SARS-CoV-2 tests in South Korea. The SARS-CoV-2 positive rates and clinical outcomes were evaluated according to the use of RAS blockers in patients with hypertension (n = 64,243). RESULTS: In total, 38,919 patients with hypertension were on RAS blockers. The SARS-CoV-2 positive rates were significantly higher in the RAS blocker group than in the control group after adjustments (adjusted odds ratio [OR], 1.22; 95% confidence interval [CI], 1.10 to 1.36; p < 0.001), and matching by propensity score (adjusted OR, 1.16; 95% CI, 1.03 to 1.32; p = 0.017). Among the 1,609 SARS-CoV-2-positive patients with hypertension, the use of RAS blockers was not associated with poor outcomes, such as mortality (adjusted OR, 0.81; 95% CI, 0.56 to 1.17; p = 0.265), and a composite of admission to the intensive care unit and mortality (adjusted OR, 0.95; 95% CI, 0.73 to 1.22; p = 0.669). Analysis in the propensity scorematched population showed consistent results. CONCLUSION: In this Korean nationwide claims dataset, the use of RAS blockers was associated with a higher risk to SARS-CoV-2 infection but not with higher mortality or other severe clinical courses.

Effect of prone positioning on oxygenation and static respiratory system compliance in COVID-19 ARDS vs. non-COVID ARDS.

BACKGROUND: Prone positioning is recommended for patients with moderate-to-severe acute respiratory distress syndrome (ARDS) receiving mechanical ventilation. While the debate continues as to whether COVID-19 ARDS is clinically different from non-COVID ARDS, there is little data on whether the physiological effects of prone positioning differ between the two conditions. We aimed to compare the physiological effect of prone positioning between patients with COVID-19 ARDS and those with non-COVID ARDS. METHODS: We retrospectively compared 23 patients with COVID-19 ARDS and 145 patients with non-COVID ARDS treated using prone positioning while on mechanical ventilation. Changes in PaO2/FiO2 ratio and static respiratory system compliance (Crs) after the first session of prone positioning were compared between the two groups: first, using all patients with non-COVID ARDS, and second, using subgroups of patients with non-COVID ARDS matched 1:1 with patients with COVID-19 ARDS for baseline PaO2/FiO2 ratio and static Crs. We also evaluated whether the response to the first prone positioning session was associated with the clinical outcome. RESULTS: When compared with the entire group of patients with non-COVID ARDS, patients with COVID-19 ARDS showed more pronounced improvement in PaO2/FiO2 ratio [adjusted difference 39.3 (95% CI 5.2-73.5) mmHg] and static Crs [adjusted difference 3.4 (95% CI 1.1-5.6) mL/cmH2O]. However, these between-group differences were not significant when the matched samples (either PaO2/FiO2-matched or compliance-matched) were analyzed. Patients who successfully discontinued mechanical ventilation showed more remarkable improvement in PaO2/FiO2 ratio [median 112 (IQR 85-144) vs. 35 (IQR 6-52) mmHg, P = 0.003] and static compliance [median 5.7 (IQR 3.3-7.7) vs. - 1.0 (IQR - 3.7-3.0) mL/cmH2O, P = 0.006] after prone positioning compared with patients who did not. The association between oxygenation and Crs responses to prone positioning and clinical outcome was also evident in the adjusted competing risk regression. CONCLUSIONS: In patients with COVID-19 ARDS, prone positioning was as effective in improving respiratory physiology as in patients with non-COVID ARDS. Thus, it should be actively considered as a therapeutic option. The physiological response to the first session of prone positioning was predictive of the clinical outcome of patients with COVID-19 ARDS.

A systematic review and meta-analysis of regional risk factors for critical outcomes of COVID-19 during early phase of the pandemic.

The mortality rates of COVID-19 vary across the globe. While some risk factors for poor prognosis of the disease are known, regional differences are suspected. We reviewed the risk factors for critical outcomes of COVID-19 according to the location of the infected patients, from various literature databases from January 1 through June 8, 2020. Candidate variables to predict the outcome included patient demographics, underlying medical conditions, symptoms, and laboratory findings. The risk factors in the overall population included sex, age, and all inspected underlying medical conditions. Symptoms of dyspnea, anorexia, dizziness, fatigue, and certain laboratory findings were also indicators of the critical outcome. Underlying respiratory disease was associated higher risk of the critical outcome in studies from Asia and Europe, but not North America. Underlying hepatic disease was associated with a higher risk of the critical outcome from Europe, but not from Asia and North America. Symptoms of vomiting, anorexia, dizziness, and fatigue were significantly associated with the critical outcome in studies from Asia, but not from Europe and North America. Hemoglobin and platelet count affected patients differently in Asia compared to those in Europe and North America. Such regional discrepancies should be considered when treating patients with COVID-19.

Evaluation of SARS-CoV-2 serology assays reveals a range of test performance.

Appropriate use and interpretation of serological tests for assessments of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure, infection and potential immunity require accurate data on assay performance. We conducted a head-to-head evaluation of ten point-of-care-style lateral flow assays (LFAs) and two laboratory-based enzyme-linked immunosorbent assays to detect anti-SARS-CoV-2 IgM and IgG antibodies in 5-d time intervals from symptom onset and studied the specificity of each assay in pre-coronavirus disease 2019 specimens. The percent of seropositive individuals increased with time, peaking in the latest time interval tested (>20 d after symptom onset). Test specificity ranged from 84.3% to 100.0% and was predominantly affected by variability in IgM results. LFA specificity could be increased by considering weak bands as negative, but this decreased detection of antibodies (sensitivity) in a subset of SARS-CoV-2 real-time PCR-positive cases. Our results underline the importance of seropositivity threshold determination and reader training for reliable LFA deployment. Although there was no standout serological assay, four tests achieved more than 80% positivity at later time points tested and more than 95% specificity.