Characterization of the Outer Membrane Vesicles of Pseudomonas aeruginosa Exhibiting Growth Inhibition against Acinetobacter baumannii.

We investigated the Pseudomonas aeruginosa (PA) outer membrane vesicles (OMVs) and their effect on Acinetobacter baumannii (AB) growth in vitro. The inhibitory effects of PA on AB were assessed using a cross-streak assay. The OMVs were extracted through high-speed centrifugation, tangential flow filtration, and ultracentrifugation and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), transmission electron microscopy (TEM), and nanoparticle tracking assays (NTAs). Proteomic analysis was conducted to compare the OMVs of different PA strains. PA022 exhibited more pronounced inhibition of AB growth compared with PA ATCC 27853. TEM confirmed the presence of OMVs in both PA022 and PA ATCC 27853, revealing phospholipid bilayer structures. The NTA revealed similar sizes and concentrations. Proteomic analysis identified 623 and 538 proteins in PA022 and PA ATCC 27853 OMVs, respectively, with significant proportions of the outer membrane and extracellular proteins, respectively. Importantly, PA022 OMVs contained six known virulence factors and motility-associated proteins. This study revealed the unique characteristics of PA OMVs and their inhibitory effects on AB growth, shedding light on their role in bacterial interactions. Proteomic analysis provides valuable insights into potential pathogenic functions and therapeutic applications against bacterial infections.

Comparison of Neutralizing Activity between Vaccinated and Unvaccinated Hospitalized COVID-19 Patients Infected with Delta, Omicron BA.1, or Omicron BA.2 Variant.

BACKGROUND: Understanding the immune response to evolving viral strains is crucial for evidence-informed public health strategies. The main objective of this study is to assess the influence of vaccination on the neutralizing activity of SARS-CoV-2 delta and omicron infection against various SARS-CoV-2 variants. METHODS: A total of 97 laboratory-confirmed COVID-19 cases were included. To assess the influence of vaccination on neutralizing activity, we measured the neutralizing activity of SARS-CoV-2 delta or omicron (BA.1 or BA.2) infection against wild-type (WT), delta, BA.1, and BA.2, with the results stratified based on vaccination status. RESULTS: The neutralizing activity against the WT, delta, and omicron variants (BA.1 and BA.2) was significantly higher in the vaccinated patients than those in the unvaccinated patients. In the unvaccinated individuals infected with the delta variant, the decrease in binding to BA.1 and BA.2 was statistically significant (3.9- and 2.7-fold, respectively) compared to the binding to delta. In contrast, vaccination followed by delta breakthrough infection improved the cross-neutralizing activity against omicron variants, with only 1.3- and 1.2-fold decreases in BA.1 and BA.2, respectively. Vaccination followed by infection improved cross-neutralizing activity against WT, delta, and BA.2 variants in patients infected with the BA.1 variant, compared to that in unvaccinated patients. CONCLUSIONS: Vaccination followed by delta or BA.1 infection is associated with improved cross-neutralizing activity against different SARS-CoV-2 variants. The enhanced protection provided by breakthrough infections could have practical implications for optimizing vaccination strategies.

Clinical and molecular predictors of mortality in patients with carbapenem-resistant Acinetobacter baumannii bacteremia: A retrospective cohort study.

BACKGROUND/PURPOSE: To investigate the virulence profiles and identify clinical and microbiological predictors of mortality in patients with carbapenem-resistant Acinetobacter baumannii (A. baumannii) bacteremia. METHODS: This retrospective cohort study enrolled adult patients with carbapenem-resistant A. baumannii (CRAB). Multivariate logistic regression was used to identify the predictors of 30-day mortality. All isolates were subjected to real-time polymerase chain reaction for virulence factors and genotyped using multilocus sequence typing. RESULTS: Among the 153 patients with CRAB bacteremia, 66 % received appropriate definitive antibiotic therapy. The in-hospital and 30-day mortality rates were 58.3 and 23.5 %, respectively. Ultimately, we enrolled 125 patients with CRAB bacteremia in the analysis, excluding early mortality cases. All CRAB isolates carried blaOXA-23 and blaOXA-51. The clinical strains belonged to 10 sequence types (STs), and the major genotypes were ST191, ST195, ST451, and ST784. The distribution of virulence factors included surface adhesion (Ata, 84.8 %; ChoP, 7.2 %), biofilm formation (OmpA, 76.8 %), killing of host cells (AbeD, 99.2 %), toxins (LipA, 99.2 %), and conjugation (BfmR, 90.4 %). In multivariate logistic regression analysis, hemodialysis due to acute kidney injury and moderate to severe thrombocytopenia were significant risk factors associated with 30-day mortality. However, microbiological factors were not significant predictors. CONCLUSIONS: Clinical factors such as hemodialysis due to acute renal injury and moderate to severe thrombocytopenia have a greater influence on mortality in CRAB bacteremia compared with microbiological factors.

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. CONCLUSION: 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.

Molecular and virulence characteristics of carbapenem-resistant Acinetobacter baumannii isolates: a prospective cohort study.

This study aimed to characterize the molecular features and virulence profiles of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates. Clinical CRAB isolates were obtained from blood cultures of adult patients with CRAB bacteremia, collected between July 2015 and July 2021 at a Korean hospital. Real-time polymerase chain reaction was used to detect 13 virulence genes, genotyping was conducted via multilocus sequence typing (MLST), and a Tenebrio molitor infection model was selected for survival analysis. Herein, 170 patients, from whom CRAB isolates were collected, showed the in-hospital mortality rate of 57.6%. All 170 clinical CRAB isolates harbored blaOXA-23 and blaOXA-51. MLST genotyping identified 11 CRAB sequence types (STs), of which ST191 was predominant (25.7%). Virulence genes were distributed as follows: basD, 58.9%; espA, 15.9%; bap, 92.4%; and ompA, 77.1%. In the T. molitor model, ST195 showed a significantly higher mortality rate (73.3% vs. 66.7%, p = 0.015) than the other groups. Our findings provide insights into the microbiological features of CRAB blood isolates associated with high mortality. We suggest a potential framework for using a T. molitor infection model to characterize CRAB virulence. Further research is warranted to elucidate the mechanisms by which virulence improves clinical outcomes.

Clinical efficacy of inhaled corticosteroids in patients with coronavirus disease 2019: A living review and meta-analysis.

Inhaled corticosteroids are known to be relatively safe for long-term use in inflammatory respiratory diseases and it has been repurposed as one of the potential therapies for outpatients with coronavirus disease 2019 (COVID-19). However, inhaled corticosteroids have not been accepted for COVID-19 as a standard therapy because of its lack of proven benefits. Therefore, this study aimed to evaluate the effectiveness of inhaled corticosteroids in patients with COVID-19. Randomized controlled trials comparing the efficacy of inhaled corticosteroid treatment in patients with COVID-19 were identified through literature electronic database searches up to March 10, 2023. Meta-analyses were conducted for predefined outcomes, and the certainty of evidence was graded using the grading of recommendations, assessment, development, and evaluation approach. Overall, seven trials (eight articles) were included in this systematic review. Compared with usual care, inhaled corticosteroids was associated with significantly improved clinical recovery at 7 and 14 days in patients with COVID-19. In subgroup analysis, only budesonide showed significant efficacy in clinical recovery, whereas no significant benefit was observed for ciclesonide. Moreover, inhaled corticosteroids use was not significantly associated with all-cause hospitalization, all-cause mortality, admission to intensive care unit, or the use of mechanical ventilation. Our systematic review used evidence with very low to moderate certainty. Although based on limited evidence, our results suggest that inhaled corticosteroids treatment, especially budesonide, improves the clinical recovery of patients with COVID-19. More trials and meta-analyses are needed to assess the efficacy of inhaled corticosteroids for COVID-19 treatment.

Clinical impact of COVID-19 in patients with carbapenem-resistant Acinetobacter baumannii bacteraemia.

The aim of this study was to evaluate the impact of coronavirus disease 2019 (COVID-19) on treatment outcomes in critically ill patients with carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infection (BSI). This single-centre, retrospective cohort study was conducted in a 1,048-bed university-affiliated tertiary hospital in the Republic of Korea from January 2021 to March 2022. The study participants included consecutive hospitalised adult patients (aged ≥18 years) in the intensive care unit with CRAB monomicrobial BSI. During the study period, a total of 70 patients were included in our study, and 24 (34.3%) were diagnosed with COVID-19. The 28-day mortality rate was 64.3%. In the multivariate Cox proportional hazard regression analysis, diagnosis of COVID-19 (hazard ratio (HR), 2.91; 95% confidence interval (CI): 1.45-5.87), neutropenia (HR, 2.76; 95% CI: 1.04-7.29), Pitt bacteraemia score (per point; HR, 1.30; 95% CI: 1.19-1.41), and appropriate definite antibiotic therapy (HR, 0.31; 95% CI: 0.15-0.62) were independent predictors of 28-day mortality in patients with CRAB BSI. In conclusion, our findings suggested that COVID-19 has a negative prognostic impact on patients with CRAB BSI. Further study is needed to investigate the specific mechanisms of how COVID-19 worsens the prognosis of CRAB infection.

Method for the Rapid Detection of SARS-CoV-2-Neutralizing Antibodies Using a Nanogel-Based Surface Plasmon Resonance Biosensor.

The efficacy of coronavirus disease 2019 (COVID-19) vaccination is closely related to the serum levels of SARS-CoV-2-neutralizing antibodies (NAb) that bind to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Therefore, the rapid and quantitative measurement of SARS-CoV-2 NAb in the sera of vaccinated individuals is essential to develop an effective vaccine and further achieve population immunity, that is, herd immunity. The plaque reduction neutralization test, the gold standard for NAb effectiveness in serological tests, is accurate but requires biosafety level 3 facilities because of the use of the virus, which hampers its application in common laboratories and clinical practice. Here, we developed a bioresponsive nanogel-based surface plasmon resonance (nSPR) platform that detects SARS-CoV-2 NAb in clinical samples without complicated pretreatment. We found that multivalent protein binding (MPB) between the nanogel-conjugated RBD protein and SARS-CoV-2 NAb yields significantly enhanced SPR signals compared to the nonspecific interference from serum proteins in the nSPR assay. The excellence of our nanogel-based SARS-CoV-2 NAb test is due to its selectivity for NAb, with resistance to all other proteins, allowing the rapid detection and quantification of NAbs in each individual. Importantly, this nSPR assay provides a NAb detection platform for easier and safer COVID-19 vaccination strategies.

Clinical efficacy and safety of SARS-CoV-2-neutralizing monoclonal antibody in patients with COVID-19: A living systematic review and meta-analysis.

This study evaluated the efficacy and safety of neutralizing monoclonal antibodies (mAbs) with usual care in patients with coronavirus disease 2019 (COVID-19). Randomized controlled trials comparing the efficacy and safety of neutralizing mAb treatment in patients with COVID-19 were identified using electronic database searches through March 10, 2023. This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Overall, 13 trials (23 articles) involving 25,646 patients were included in this systematic review. Compared with usual care, neutralizing mAbs were associated with significantly reduced all-cause mortality in outpatients with COVID-19 (pooled risk ratios [RR], 0.41; 95% confidence interval (CI), 0.20-0.83; 12 studies), but not in inpatients. In the subgroup analysis, only outpatients infected prior to the emergence of Delta variant or those with mAb-VOC match had significantly reduced mortality, while no significant benefit was observed in patients infected with Delta and post-Delta variants or mAb-VOC mismatch. Moreover, the rate of hospitalization and number of hospital visits had significantly reduced only in outpatients infected prior to the emergence of the Delta variant and those with mAb-VOC match. Our systematic review used majority of the high-certainty evidence. Our study found neutralizing mAbs were beneficial for outpatients infected prior to Delta variant or mAb-VOC match. In the face of the continuous emergence of new COVID-19 variants, additional clinical data are needed to determine whether neutralizing mAb treatment will be effective for the newly emerging variants.

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.

Carbapenem Use in the Last Days of Life: A Nationwide Korean Study.

The appropriate use of carbapenem is a critical concern for patient safety and public health, and is a national priority. We investigated the nationwide status of carbapenem prescription in patients within their last 14 days of life to guide judicious-use protocols from the previous study comprised of 1350 decedents. Carbapenem use was universally controlled through computerised authorisation system at all centres during the study period. Carbapenem prescribing patterns and their optimality were evaluated. A total of 1201 patients received antimicrobial agents within the last two weeks of their lives, of whom 533 (44.4%) received at least one carbapenem. The median carbapenem treatment duration was seven days. Of the 533 patients receiving carbapenems, 510 (95.7%) patients had microbiological samples drawn and 196 (36.8%) yielded carbapenem-resistant pathogens. A total of 200 (37.5%) patients were referred to infectious disease (ID) specialists. Of the 333 patients (62.5%) who did not have ID consultations, 194 (58.2%) were assessed as "not optimal", 79 (23.7%) required escalation, 100 (30.0%) required de-escalation, and 15 (4.5%) were discontinued. Notwithstanding the existing antibiotic restriction program system, carbapenems are commonly prescribed to patients in their last days of life.

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. CONCLUSION: 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.

Clinical prediction rule for identifying older patients with toxigenic clostridioides difficile at the time of hospital admission.

BACKGROUND: This study aimed to develop and validate a clinical prediction rule to screen older patients at risk of being toxigenic Clostridioides difficile carriers at the time of hospital admission. METHODS: This retrospective case-control study was performed at a university-affiliated hospital. Active surveillance using a real-time polymerase chain reaction (PCR) assay for the toxin genes of C. difficile was conducted among older patients (≥ 65 years) upon admission to the Division of Infectious Diseases of our institution. This rule was drawn from a derivative cohort between October 2019 and April 2021 using a multivariable logistic regression model. Clinical predictability was evaluated in the validation cohort between May 2021 and October 2021. RESULTS: Of 628 PCR screenings for toxigenic C. difficile carriage, 101 (16.1%) yielded positive findings. To establish clinical prediction rules in the derivation cohort, the formula was derived using significant predictors for toxigenic C. difficile carriage at admission, such as septic shock, connective tissue diseases, anemia, recent use of antibiotics, and recent use of proton-pump inhibitors. In the validation cohort, the sensitivity, specificity, and positive and negative predictive values of the prediction rule, based on a cut-off value of ≥ 0.45, were 78.3%, 70.8%, 29.5%, and 95.4%, respectively. CONCLUSION: This clinical prediction rule for identifying toxigenic C. difficile carriage at admission may facilitate the selective screening of high-risk groups. To implement it in a clinical setting, more patients from other medical institutions need to be prospectively examined.

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 multidrug-resistant 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.

Developing Core Elements and Checklist Items for Implementing Antimicrobial Stewardship Programs in Korean General Hospitals: A Modified Delphi Survey.

BACKGROUND: Antimicrobial stewardship programs (ASPs) aim to optimize antimicrobial use by minimizing the spread of antimicrobial resistance. The core elements for implementing ASPs in healthcare facilities have been developed by the World Health Organization, international research group and government agencies of various countries. However, to date, there is no documented core elements for implementation of ASP in Korea. This survey aimed to establish a national consensus on a set of core elements and their related checklist items for the implementation of ASPs in Korean general hospitals. MATERIALS AND METHODS: The survey was conducted from July 2022 to August 2022 by the Korean Society for Antimicrobial Therapy with support from the Korea Disease Control and Prevention Agency. A literature review was conducted by searching Medline and relevant websites to retrieve a list of core elements and checklist items. These core elements and checklist items were evaluated by a multidisciplinary panel of experts using a structured modified Delphi consensus procedure, using two-step survey included online in-depth questionnaires and in-person meeting. RESULTS: The literature review identified 6 core elements (Leadership commitment, Operating system, Action, Tracking, Reporting, and Education) and 37 related checklist items. Fifteen experts participated in the consensus procedures. Ultimately, all 6 core elements were retained, and 28 checklist items were proposed, all with ≥80% agreement; in addition 9 items were merged into 2 items, 2 items were deleted, and 15 items were rephrased. CONCLUSION: This Delphi survey provides useful indicators for the implementation of ASP in Korea and suggests national policy improvement about the barriers (e.g., shortage of staffing and financial support) existing in Korea for optimal implementation of ASPs.

Gram-Negative Bacteria's Outer Membrane Vesicles.

Outer membrane vesicles (OMVs) are spherical bilayered nanoparticles derived from the outer layer of Gram-negative bacteria. Bacteria communicate with nearby bacteria, their environment, and the cells of their host by secreting OMVs, which are essential for their survival. OMVs also play a critical role in bacterial pathogenesis since they are loaded with virulence factors, toxins, and enzymes. OMVs may modulate the immune response of the host by initiating inflammation through cytokine production and activating the innate immune response. OMVs also contribute to the resistance of bacteria to antibiotics by carrying antibiotic-degrading enzymes and acting as natural protection barriers. Concerns have also been raised regarding OMVs mediating the transfer of antibiotic resistance. Due to their advantageous properties, OMVs are attractive platforms for vaccine discovery and drug delivery research. In this review, we discuss the fundamental structure and biogenesis mechanisms of OMVs as well as their multifaceted roles in bacterial infection pathogenesis and host immune responses. We also discuss application examples of OMVs.

Predictive Value of Reactogenicity for Anti-SARS-CoV-2 Antibody Response in mRNA-1273 Recipients: A Multicenter Prospective Cohort Study.

Messenger RNA (mRNA) vaccination was developed to mitigate the coronavirus disease 2019 pandemic. However, data on antibody kinetics and factors influencing these vaccines' immunogenicity are limited. We conducted a prospective study on healthy young adults who received two doses of the mRNA-1273 vaccine at 28-day intervals. After each dose, adverse events were prospectively evaluated, and blood samples were collected. The correlation between humoral immune response and reactogenicity after vaccination was determined. In 177 participants (19-55 years), the geometric mean titers of anti-S IgG antibody were 178.07 and 4409.61 U/mL, while those of 50% neutralizing titers were 479.95 and 2851.67 U/mL four weeks after the first and second vaccine doses, respectively. Anti-S IgG antibody titers were not associated with local reactogenicity but were higher in participants who experienced systemic adverse events (headache and muscle pain). Antipyretic use was an independent predictive factor of a robust anti-SARS-CoV-2 antibody response after receiving both vaccine doses. Systemic reactogenicity after the first dose influenced antibody response after the second dose. In conclusion, mRNA-1273 induced a robust antibody response in healthy young adults. Antipyretic use did not decrease the anti-SARS-CoV-2 antibody response after mRNA-1273 vaccination.

Rhamnetin, a Natural Flavonoid, Ameliorates Organ Damage in a Mouse Model of Carbapenem-Resistant Acinetobacter baumannii-Induced Sepsis.

In sepsis, the persistence of uncontrolled inflammatory response of infected host cells eventually leads to severe lung and organ failure and, ultimately, death. Carbapenem-resistant Acinetobacter baumannii (CRAB), causative bacteria of sepsis and lung failure in acute cases, belongs to a group of critical pathogens that cannot be eradicated using the currently available antibiotics. This underlines the necessity of developing new modes of therapeutics that can control sepsis at the initial stages. In this study, we investigated the anti-inflammatory activities in vitro and in vivo and the antiseptic effects of rhamnetin, a naturally occurring flavonoid. We found that among its isoforms, the potency of rhamnetin was less explored but rhamnetin possessed superior anti-inflammatory activity with least cytotoxicity. Rhamnetin showed significant anti-inflammatory effects in lipopolysaccharide-, CRAB-, and Escherichia coli (E. coli)-stimulated mouse macrophages by inhibiting the release of interleukin-6 and nitric oxide. In a mouse model of sepsis infected with clinically isolated CRAB or E. coli, rhamnetin significantly reduced the bacterial burden in the organs. In addition, normalized pro-inflammatory cytokine levels in lung lysates and histological analysis of lung tissue indicated alleviation of lung damage. This study implies that a potent natural product such as rhamnetin could be a future therapeutic for treating carbapenem-resistant gram-negative sepsis.

Maternal and Neonatal Outcomes in Pregnant Women With Coronavirus Disease 2019 in Korea.

BACKGROUND: This study aimed to describe the maternal, obstetrical, and neonatal outcomes in pregnant women with coronavirus disease 2019 (COVID-19) and identify the predictors associated with the severity of COVID-19. METHODS: This multicenter observational study included consecutive pregnant women admitted because of COVID-19 confirmed using reverse transcriptase-polymerase chain reaction (RT-PCR) test at 15 hospitals in the Republic of Korea between January 2020 and December 2021. RESULTS: A total of 257 women with COVID-19 and 62 newborns were included in this study. Most of the patients developed this disease during the third trimester. Nine patients (7.4%) developed pregnancy-related complications. All pregnant women received inpatient treatment, of whom 9 (3.5%) required intensive care, but none of them died. The gestational age at COVID-19 diagnosis (odds ratio [OR], 1.096, 95% confidence interval [CI], 1.04-1.15) and parity (OR, 1.703, 95% CI, 1.13-2.57) were identified as significant risk factors of severe diseases. Among women who delivered, 78.5% underwent cesarean section. Preterm birth (38.5%), premature rupture of membranes (7.7%), and miscarriage (4.6%) occurred, but there was no stillbirth or neonatal death. The RT-PCR test of newborns' amniotic fluid and umbilical cord blood samples was negative for severe acute respiratory syndrome coronavirus 2. CONCLUSION: At the time of COVID-19 diagnosis, gestational age and parity of pregnant women were the risk factors of disease severity. Vertical transmission of COVID-19 was not observed, and maternal severity did not significantly affect the neonatal prognosis.

Hyperglycemia and Hypoglycemia Are Associated with In-Hospital Mortality among Patients with Coronavirus Disease 2019 Supported with Extracorporeal Membrane Oxygenation.

Metabolic abnormalities, such as preexisting diabetes or hyperglycemia or hypoglycemia during hospitalization aggravated the severity of COVID-19. We evaluated whether diabetes history, hyperglycemia before and during extracorporeal membrane oxygenation (ECMO) support, and hypoglycemia were risk factors for mortality in patients with COVID-19. This study included data on 195 patients with COVID-19, who were aged ≥19 years and were treated with ECMO. The proportion of patients with diabetes history among nonsurvivors was higher than that among survivors. Univariate Cox regression analysis showed that in-hospital mortality after ECMO support was associated with diabetes history, renal replacement therapy (RRT), and body mass index (BMI) < 18.5 kg/m2. Glucose at admission >200 mg/dL and glucose levels before ventilator >200 mg/dL were not associated with in-hospital mortality. However, glucose levels before ECMO >200 mg/dL and minimal glucose levels during hospitalization <70 mg/dL were associated with in-hospital mortality. Multivariable Cox regression analysis showed that glucose >200 mg/dL before ECMO and minimal glucose <70 mg/dL during hospitalization remained risk factors for in-hospital mortality after adjustment for age, BMI, and RRT. In conclusion, glucose >200 mg/dL before ECMO and minimal glucose level <70 mg/dL during hospitalization were risk factors for in-hospital mortality among COVID-19 patients who underwent ECMO.