SARS-CoV-2 nucleocapsid protein, rather than spike protein, triggers a cytokine storm originating from lung epithelial cells in patients with COVID-19.

PURPOSE: The aim of this study was to elucidate the factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that may initiate cytokine cascades and correlate the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with their serum cytokine profiles. METHODS: Recombinant baculoviruses displaying SARS-CoV-2 spike or nucleocapsid protein were constructed and transfected into A549 cells and THP-1-derived macrophages, to determine which protein initiate cytokine release. SARS-CoV-2-specific antibody titers and cytokine profiles of patients with COVID-19 were determined, and the results were associated with their clinical characteristics, such as development of pneumonia or length of hospital stay. RESULTS: The SARS-CoV-2 nucleocapsid protein, rather than the spike protein, triggers lung epithelial A549 cells to express IP-10, RANTES, IL-16, MIP-1α, basic FGF, eotaxin, IL-15, PDGF-BB, TRAIL, VEGF-A, and IL-5. Additionally, serum CTACK, basic FGF, GRO-α, IL-1α, IL-1RA, IL-2Rα, IL-9, IL-15, IL-16, IL-18, IP-10, M-CSF, MIF, MIG, RANTES, SCGF-ß, SDF-1α, TNF-α, TNF-ß, VEGF, PDGF-BB, TRAIL, ß-NGF, eotaxin, GM-CSF, IFN-α2, INF-γ, and MCP-1 levels were considerably increased in patients with COVID-19. Among them, patients with pneumonia had higher serum IP-10 and M-CSF levels than patients without. Patients requiring less than 3 weeks to show negative COVID-19 tests after contracting COVID-19 had higher serum IP-10 levels than the remaining patients. CONCLUSION: Our study revealed that nucleocapsid protein, lung epithelial cells, and IP-10 may be potential targets for the development of new strategies to prevent, or control, severe COVID-19.

In vitro and in vivo activities of imipenem combined with BLI-489 against class D ß-lactamase-producing Acinetobacter baumannii.

BACKGROUND: According to our preliminary study, BLI-489 has the potential to inhibit the hydrolysing activity of OXA-51-like ß-lactamase produced by carbapenem-resistant Acinetobacter baumannii (CRAb). OBJECTIVES: In the present study, the in vitro and in vivo activities of imipenem combined with BLI-489 against CRAb producing carbapenem-hydrolysing class D ß-lactamases (CHDLs), namely OXA-23, OXA-24, OXA-51 and OXA-58, were determined. METHODS: A chequerboard analysis of imipenem and BLI-489 was performed using 57 and 7 clinical CRAb isolates producing different CHDLs and MBLs, respectively. Four representative strains harbouring different CHDL genes were subjected to a time-kill assay to evaluate the synergistic effects. An in silico docking analysis was conducted to simulate the interactions between BLI-489 and the different families of CHDLs. The in vivo activities of this combination were assessed using a Caenorhabditis elegans survival assay and a mouse pneumonia model. RESULTS: Chequerboard analysis showed that imipenem and BLI-489 had a synergistic effect on 14.3, 92.9, 100, 16.7 and 100% of MBL-, OXA-23-, OXA-24-like-, OXA-51-like- and OXA-58-producing CRAb isolates, respectively. In the time-kill assay, imipenem and BLI-489 showed synergy against OXA-24-like-, OXA-51-like- and OXA-58-, but not OXA-23-producing CRAb isolates after 24 h. The in silico docking analysis showed that BLI-489 could bind to the active sites of OXA-24 and OXA-58 to confer strong inhibition activity. The combination of imipenem and BLI-489 exhibited synergistic effects for the rescue of CRAb-infected C. elegans and mice. CONCLUSIONS: Imipenem combined with BLI-489 has synergistic effects against CHDL-producing CRAb isolates.

Successful treatment of 28 patients with coronavirus disease 2019 at a medical center in Taiwan.

BACKGROUND: Coronavirus disease-2019 (COVID-19) is a worldwide pandemic. We present the clinical characteristics and outcomes of 28 COVID-19 patients treated in our hospital in Taiwan. METHODS: Patients with COVID-19, confirmed by positive real-time reverse-transcriptase polymerase chain reaction results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral nucleic acids from oropharyngeal swab specimens between February 4, 2020 and July 6, 2020, were enrolled. Their clinical characteristics and outcomes were reviewed. RESULTS: Seventeen of the 28 patients (60.7%) had pneumonia. The most frequent symptoms were cough (n = 23, 82.1%) and fever (n = 17, 60.7%). The development of pneumonia was associated with age ≥40 years (p < 0.024), body mass index (BMI) ≥25 kg/m2 (p = 0.014), fever (p = 0.007), shortness of breath (p = 0.036), chills ((p = 0.047), and lower platelet counts (<200,000/µL) (p = 0.007). Increased quarantine duration was associated with age ≥40 years (p = 0.026), Charlson index ≥1 (p = 0.037), lower lymphocyte (<1500/uL; p = 0.028) or platelet counts (<200,000/µL) (p = 0.016), lower serum sodium (<140 mEq/L; p = 0.006), and higher C-reactive protein (CRP) level (≥1 mg/dl; p = 0.04). Treatment with hydroxychloroquine or in combination with other medicines did not reduce the quarantine duration. All 28 patients recovered with a median quarantine duration of 27.2 days. CONCLUSION: COVID-19 patients with older age, higher BMI, fever, chills or shortness of breath, lower serum sodium level, lower platelet or lymphocyte count, and higher CRP level may be associated with developing pneumonia or longer quarantine duration.

Scrub typhus and depression: a nationwide cohort analysis.

BACKGROUND: Studies on the relationship between depression and scrub typhus are limited. We conducted a retrospective cohort study to investigate whether scrub typhus is a risk factor for depression. METHODS: Using Taiwan's National Health Insurance Research Database, this study investigated the incidence of depression, and its risk factors, in patients diagnosed with scrub typhus between 2000 and 2010. Scrub typhus patients who did not have a history of depression before the index date were enrolled. For each patient with scrub typhus, four controls without a history of scrub typhus and depression were randomly selected and frequency matched by sex, age, year of the index date, and comorbidities. The follow-up period was from the time of initial scrub typhus diagnosis to the date of diagnosis of depression, censoring, or December 31, 2010. Cox proportional hazards regression models were used to analyze the risk of depression according to sex, age, and comorbidities. RESULTS: The study comprised a 5238-patient scrub typhus group and a 20,952-patient non-scrub typhus group with similar sex and age distributions. During the follow-up period, the cumulative incidence of depression was higher in the scrub typhus than the non-scrub typhus group (log-rank test P < 0.001). In the scrub typhus group, 45 patients developed depression, yielding an incidence rate of 1.67 per 1000 person-years, and in the non-scrub typhus group, 117 patients developed depression, yielding an incidence rate of 1.08 per 1000 person-years. This yielded a crude hazard ratio (HR) of 1.55 (95% confidence interval [CI] 1.41-1.70) and adjusted HR (aHR) of 1.56 (95% CI 1.42-1.71). Compared with the non-scrub typhus group, the risk of depression in the scrub typhus group was higher in patients of both sexes (men: aHR = 1.46, 95% CI 1.29-1.64; women: aHR = 1.68, 95% CI 1.45-1.96), in patients aged younger than 65 (≤ 49 years: aHR = 1.95, 50-64 years: aHR = 1.73), and in patients without comorbidities (aHR = 2.06, 95% CI 1.85-2.29). CONCLUSIONS: The risk of depression was 1.56-fold higher in patients with scrub typhus than in the general population.

Risk of Mortality of Catheter-Related Bloodstream Infections Caused by Acinetobacter Species: Is Early Removal of the Catheters Associated With a Better Survival Outcome?

PURPOSE: Bloodstream infections (BSIs) caused by Acinetobacter species have been extensively reported, however, which majorly focused on respiratory tract infections. The risk of mortality and the effect of early catheter removal on survival in catheter-related BSIs (CRBSIs) caused by Acinetobacter spp. remain unclear. This study aims to investigate that. METHODS: This is a retrospective multicentric study conducted in Taiwan from 2012 to 2014. Patients with at least 1 positive blood culture and catheter culture for the same Acinetobacter spp., showing symptoms and signs of CRBSIs, were included (n = 119). Risk factors for 30-day mortality were analyzed using a logistic regression model. The characteristics of patients with early catheter removal (within 48 hours after CRBSIs) were compared to those without removal matching for age, sex, and disease severity. RESULTS: There were no differences in 30-day mortality with regard to causative Acinetobacter spp., catheter type, site, and appropriateness of antimicrobial therapy. Patients with higher Acute Physiologic and Chronic Health Evaluation (APACHE) II scores (odds ratio [OR]: 1.12; 95% confidence interval [CI]: 1.02-1.23; P = .014), shock (OR: 6.43; 95% CI: 1.28-32.33; P = .024), and longer hospitalization before CRBSIs (OR: 1.04; 95% CI: 1.00-1.08; P = .027) had a significantly higher 30-day mortality rate. Early removal of catheters after CRBSIs was not associated with better survival benefits. CONCLUSION: Higher disease severity (APACHE II score), shock, and longer hospitalization before bacteremia were independently associated with a higher 30-day mortality in CRBSIs caused by Acinetobacter spp. In previous published guidelines, infected catheters were suggested to be removed in CRBSIs caused by gram-negative bacilli. Even though early removal of catheters did not associate with a better survival outcome in current results, it should be judiciously evaluated according to the clinical conditions and risks individually. For better elucidation of these issues, further well-controlled prospective study may be warranted.

Individual or Combined Effects of Meropenem, Imipenem, Sulbactam, Colistin, and Tigecycline on Biofilm-Embedded Acinetobacter baumannii and Biofilm Architecture.

Acinetobacter baumannii biofilms are difficult to eradicate. We investigated the effects of meropenem (2 mg/liter), imipenem (2 mg/liter), sulbactam (4 mg/liter), colistin (2 mg/liter), and tigecycline (2 mg/liter), alone or in combination, on biofilm-embedded carbapenem-resistant and carbapenem-susceptible A. baumannii (CRAb and CSAb, respectively) cells, as well as on the architecture of the biofilms. A. baumannii ATCC 15151 (Ab15151) and its OXA-82-overproducing transformant, along with two clinical CSAb and two clinical CRAb isolates of differing clonalities, were used. The minimal bactericidal concentrations for biofilm-embedded cells of the six tested isolates were >50-fold those of their planktonic cells. When used individually, meropenem exhibited a higher killing effect than the other four antimicrobials on biofilm-embedded CSAb cells in the colony biofilm assay. For two clinical CRAb isolates, meropenem plus sulbactam or sulbactam plus tigecycline showed >100-fold the bactericidal effect exhibited by these agents used alone after 48 h of treatment. The effect of antimicrobials on the architecture of Ab15151 biofilm emitting green fluorescence was determined by confocal laser scanning microscopy using COMSTAT software. Significant decreases in the maximum biofilm thickness were observed after exposure to meropenem and imipenem. Meropenem plus sulbactam significantly decreased the biomass and mean thickness and increased the roughness coefficient of biofilms, but sulbactam plus tigecycline only decreased the maximum and mean biofilm thickness compared to any of these agents used alone. Meropenem was active against biofilm-embedded CSAb, whereas meropenem plus sulbactam exhibited synergism against biofilm-embedded CRAb and caused significantly more damage to the biofilm architecture than did any of the agents used alone.

In vitro activity of SecA inhibitors in combination with carbapenems against carbapenem-hydrolysing class D ß-lactamase-producing Acinetobacter baumannii.

OBJECTIVES: According to our previous study, OXA-58 translocates to the periplasm via the Sec pathway in carbapenem-resistant Acinetobacter baumannii (CRAb). In the present study, carbapenem-hydrolysing class D ß-lactamases (CHDLs) belonging to the OXA-23, OXA-40 and OXA-51 families were examined to determine whether they are also Sec-dependent. Additionally, the effects of SecA inhibitors combined with carbapenems against CHDL-producing CRAb were examined. METHODS: Cell fractionation and western blot analyses were performed to detect periplasmic His-tagged CHDLs. A chequerboard analysis with pairwise combinations of carbapenems (imipenem or meropenem) and SecA inhibitors (rose bengal, sodium azide or erythrosin B) was performed using six clinical CRAb isolates harbouring different CHDL genes. The fractional inhibitory concentration (FIC) index was determined. The combination with the lowest FIC index was subjected to a time-kill analysis to examine synergistic effects. RESULTS: In an in silico analysis, the CHDLs OXA-23, OXA-40 and OXA-51 were preferentially translocated via the Sec system. The SecA inhibitor rose bengal decreased periplasmic translocation of His-tagged OXA-23 and OXA-83 (belonging to the OXA-51 family), but not OXA-72 (belonging to the OXA-40 family) from ATCC 15151 transformants. Imipenem or meropenem with rose bengal showed synergistic effects (FIC index, ≤0.5) for six and four clinical isolates, respectively. Imipenem or meropenem with sodium azide showed no interactions (FIC index, 0.5-4) against all clinical isolates. Imipenem and rose bengal had the lowest FIC index and showed synergy at 24 h in the time-kill assay. CONCLUSIONS: Combinations of SecA inhibitors and carbapenems have synergistic effects against CHDL-producing CRAb.

A retrospective study of the incidence, clinical characteristics, identification, and antimicrobial susceptibility of bacteremic isolates of Acinetobacter ursingii.

BACKGROUND: Acinetobacter ursingii bacteremia is rarely reported. We investigated the incidence and clinical features of A. ursingii bacteremia, performance of the identification system, and antimicrobial susceptibility of the isolates. Acinetobacter ursingii bacteremia patients were compared with A. baumannii bacteremia patients. METHODS: In this 9-year retrospective study, A. ursingii was identified using 16S rRNA and 16S-23S rRNA internal transcribed spacer sequence analysis. The performances of the Vitek 2, Phoenix, and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometer systems for identifying isolates were tested. Pulsed-field gel electrophoresis (PFGE) was used to determine the clonality of the isolates. The minimal inhibitory concentrations of the antimicrobials were determined using the Vitek 2 system. RESULTS: Nineteen patients were identified. Acinetobacter ursingii was noted in 1.5-5.2 % of all Acinetobacter bacteremia cases. For the PFGE analysis, two isolates had smeared DNA, two had 93 % similarity, and 15 had similarity <80 %. Among 16 patients with complete medical records, 10 (62.5 %) had no identifiable source of A. ursingii bacteremia. Most patients (n = 12) had underlying malignant disease. Patients with A. ursingii bacteremia had lower Acute Physiology and Chronic Health Evaluation II scores than those with A. baumannii bacteremia (median [interquartile range], 17.1 [10.0-24.7] vs. 24.9 [14.6-35.1]). Patients with A. ursingii bacteremia were also less likely admitted to the intensive care unit than patients with A. baumannii bacteremia (18.8 % vs 63.5 %, p value < 0.01). About half of the patients with A. ursingii (50.8 %) and A. baumannii bacteremia (62.5 %) had received inappropriate antimicrobial therapy within 48 h after bacteremia onset. However, patients with A. ursingii bacteremia had significantly lower 14-day (6.25 % vs 29.8 %, p value = 0.04) and 28-day mortality rates (6.25 % vs 37.3 %, p value = 0.02) than patients with A. baumannii bacteremia. Nine isolates (47.4 %) were correctly identified as A. ursingii and the other 10 isolates (52.6 %) were incorrectly identified as A. lwoffii by the Vitek 2 system. The Phoenix system incorrectly identified all 19 isolates. The MALDI-TOF mass spectrometer system correctly identified all 19 isolates. All the A. ursingii isolates were resistant or showed intermediate susceptibility to ceftriaxone and ceftazidime, but were susceptible to levofloxacin and imipenem. CONCLUSIONS: Acinetobacter ursingii is a rare pathogen that mostly caused primary bacteremia in patients with malignancies. Patients with A. ursingii bacteremia had significantly lower disease severity and mortality rates than patients with A. baumannii bacteremia.

Monitoring coronavirus disease progression and clinical impact through quantitative viral load testing.

BACKGROUND: The viral load (VL) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals is critical for improving clinical treatment strategies, care, and decisions. Several studies have reported that the initial SARS-CoV-2 VL is associated with disease severity and mortality. Cycle threshold (Ct) values and/or copies/mL are often used to quantify VL. However, a multitude of platforms, primer/probe sets of different SARS-CoV-2 target genes, and reference material manufacturers may cause inconsistent interlaboratory interpretations. The first International Standard for SARS-CoV-2 RNA quantitative assays has allowed diagnostic laboratories to transition SARS-CoV-2 VL results into international units per milliliter (IU/mL). The Cobas SARS-CoV-2 Duo quantitative assay provides VL results expressed in IU/mL. MATERIALS AND METHODS: We enrolled 145 and 50 SARS-CoV-2-positive, hospitalized and 50-negative individuals at the Tri-Service General Hospital, Taiwan from January to May 2022. Each participant's electronic medical record was reviewed to determine asymptomatic, mild, moderate, and severe cases. Nasopharyngeal swabs were collected using universal transport medium. We investigated the association of SARS-CoV-2 VL with disease severity using the Cobas SARS-CoV-2 Duo quantitative assay and its functionality in clinical assessment and decision making to further improve clinical treatment strategies. Limit of detection (LOD) was assessed. RESULTS: All 50 SARS-CoV-2-negative samples confirmed negative for SARS-CoV-2, demonstrating 100 % specificity of the Cobas SARS-CoV-2 Duo assay. Patients with severe symptoms had longer hospital stays, and the length of hospital stay (30.56 days on average) positively correlated with the VL (8.22 ± 1.21 log10 IU/mL). Asymptomatic patients had the lowest VL (5.54 ± 2.06 log10 IU/mL) at admission and the shortest hospital stay (14.1 days on average). CONCLUSIONS: VL is associated with disease severity and duration of hospitalization; therefore, its quantification should be considered when making clinical care decisions and treatment strategies. The Cobas SARS-CoV-2 Duo assay provides a commutable unitage IU/mL for interlaboratory interpretations.

Boosting with Multiple Doses of mRNA Vaccine after Priming with Two Doses of Protein Subunit Vaccine MVC-COV1901 Elicited Robust Humoral and Cellular Immune Responses against Emerging SARS-CoV-2 Variants.

Confronted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, such as Delta and Omicron, with high infectivity and immune evasion capacity, vaccination remains the most effective tool to prevent infection and severe illness. However, heterologous vaccination of mRNA vaccines primed with protein subunit vaccines had not been evaluated before the current study. Since subunit vaccine MVC-COV1901 (MVC) has been granted emergency use authorization in Taiwan, in this study, we explored the humoral and cellular immune responses to additional third (2× MVC/Mod) and fourth (2× MVC/2× Mod) doses of mRNA-1273 (Mod) after priming with two doses of subunit vaccine MVC against the emerging variants. We found a 12.3- to 16.1-fold increase in antibodies targeting the receptor binding domain (RBD) of the Delta variant with 2× MVC/Mod compared to two doses of MVC (2× MVC) or AZD1222 (2× AZ) regimens and a 26- to 32.2-fold improvement in neutralizing potency against the Omicron variant (BA.1). Besides, the numbers of gamma interferon (IFN-γ)-secreting T cells induced by 2× MVC/Mod were also elevated 3.5-fold and 3.7- to 4.3-fold for the wild type and Delta variant. However, boosting with a fourth dose of Mod (2× MVC/2× Mod) after the 2× MVC/Mod regimen failed to significantly improve the immune responses. Moreover, all vaccination schedules showed reduced neutralizing activity against the Omicron variant. Collectively, our results suggested that the third or fourth dose booster vaccination with mRNA vaccine after priming with two doses of protein subunit vaccine could elicit stronger humoral and cellular immune responses. These findings could provide a future global heterologous boosting strategy against COVID-19. IMPORTANCE Vaccination is the most important strategy to combat the COVID-19 outbreak; however, it remains to be determined whether heterologous prime-boost regimens could induce equal or even stronger immune responses against SARS-CoV-2. Here, we showed that boosting the additional doses of mRNA-1273 (Mod) priming with two doses of MVC-COV1901 (MVC) (2× MVC/Mod) improved humoral and cellular immunity compared to two doses of AZD1222 (2× AZ) or MVC (2× MVC) against SARS-CoV-2 variants. However, the Omicron variant showed strong immune evasion ability for all vaccination schedules. Our findings provided evidence supporting that heterologous vaccination by boosting with mRNA vaccine after priming with two doses of protein subunit vaccine could strongly promote humoral and cellular immune responses against the emerging SARS-CoV-2 variants.

Clinical characteristics analysis of COVID-19 patients from the first significant community outbreak by SARS-CoV-2 variant B.1.1.7 in Taiwan as experienced from a single northern medical center.

BACKGROUND/PURPOSE: Clinical characteristics of patients in the first community outbreak of coronavirus disease 2019 (COVID-19) by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant B.1.1.7 in Taiwan have not been characterized. METHODS: SARS-CoV-2 positive specimens from inpatients between May 7 and June 15 in 2021were screen for SARS-CoV-2 B.1.1.7 lineage by VirSNiP assay. Clinical characteristics were reviewed and compared with those from Feb 1 to April 30, 2020 and from Jan 1 to March 31, 2022. RESULTS: One hundred forty-one inpatients from May 7 to June 15, 2021 infected with SARS-CoV-2 B.1.1.7 lineage were included. The major presenting symptoms were fever (88.7%) and cough (59.6%). Incidence of relevant complications including pulmonary embolism, simultaneous infections with bacteria, virus, and fungi were 0.7%, 12.8%, 13.5%, and 2.1%, respectively. Old age, high Charlson comorbidity index, short of breath, and initial critical illness were independently associated with 28-day mortality (all p < 0.05). In comparison to COVID-19 inpatients from Feb 1 to April 30, 2020, patients from the outbreak by SARS-CoV-2 B.1.1.7 lineage were older, more severe in disease condition, higher mortality but less obvious initial presenting symptoms. After implementation of nationwide vaccination campaign in the next half year of 2021, COVID-19 inpatients from Jan 1 to March 31 in 2022 indicated less severe diseases than those infected with SARS-CoV-2 B.1.1.7 lineage. CONCLUSION: COVID-19 inpatients by SARS-CoV-2 variant B.1.1.7 with old age, multiple comorbidities, and more severe disease conditions were associated with increased mortality. Vaccination for this vulnerable populations may be helpful.

Humoral, Cellular and Cytokine Immune Responses Against SARS-CoV-2 Variants in COVID-19 Convalescent and Confirmed Patients With Different Disease Severities.

Objectives: To assess humoral and cellular immune responses against SARS-CoV-2 variants in COVID-19 convalescent and confirmed patients, to explore the correlation between disease severity, humoral immunity, and cytokines/chemokines in confirmed patients, and to evaluate the ADE risk of SARS-CoV-2. Methods: Anti-RBD IgG were quantified using an ELISA. Neutralization potency was measured using pseudovirus and real virus. Cellular immunity was measured using ELISpot. Cytokine/chemokine levels were detected using multiplex immunoassays. In vitro ADE assays were performed using Raji cells. Results: One-month alpha convalescents exhibited spike-specific antibodies and T cells for alpha and delta variants. Notably, the RBD-specific IgG towards the delta variant decreased by 2.5-fold compared to the alpha variant. Besides, serum from individuals recently experienced COVID-19 showed suboptimal neutralizing activity against the delta and omicron variants. Humoral immune response, IL-6, IP-10 and MCP-1 levels were greater in patients with severe disease. Moreover, neither SARS-CoV-1 nor SARS-CoV-2 convalescent sera significantly enhanced SARS-CoV-2 pseudovirus infection. Conclusions: Significant resistance of the delta and omicron variants to the humoral immune response generated by individuals who recently experienced COVID-19. Furthermore, there was a significant correlation among disease severity, humoral immune response, and specific cytokines/chemokine levels. No evident ADE was observed for SARS-CoV-2.

Hospital-acquired infections in patients hospitalized with COVID-19: First report from Taiwan.

BACKGROUND: Coronavirus disease 2019 (COVID-19) inpatients may acquire infections from other pathogens during hospital admission. This is the first research on this subject to be reported from Taiwan. METHODS: Confirmed COVID-19 inpatients were enrolled in this study from January 1, 2020 to July 31, 2021. Various types of pathogens in COVID-19 inpatients, with hospital-acquired infections, were identified and analyzed. The clinical characteristics of COVID-19 patients with and without hospital-acquired infections were reviewed and compared. RESULTS: Of the 204 patients included in the study, 32 (15.7%) patients experienced at least one infectious episode. Of 113 recorded episodes of infection, the predominant type was bacterial (88 of 113 infections, 77.9%); the most frequently isolated bacteria were Acinetobacter spp., followed by Stenotrophomonas maltophilia . With regard to viral infections (19 of 113, 16.8%), the Epstein-Barr virus ranked first place among the identified viruses. Four (3.5%) and 2 (1.8%) of 113 infectious episodes were caused by fungi and atypical pathogens. A multivariate analysis revealed that steroid use was an independent factor in hospital-acquired infections (odds ratio [OR], 6.97; 95% confidence interval [CI], 1.15-42.43; p = 0.035). Patients with hospital-acquired infections were associated with increased 28-day and in-hospital mortality (18.8% vs 5.8% and 31.3% and 5.8%; p = 0.023 and <0.01, respectively), and a longer hospital stay (34 vs 19 days; p < 0.001), compared to those without hospital-acquired infections. CONCLUSION: Our study revealed the unique local epidemiology of hospital-acquired infections among COVID-19 inpatients in Taiwan. These patients were associated with increased mortality and prolonged hospital admissions.

Clinical Characteristics of COVID-19 Patients and Application to an Artificial Intelligence System for Disease Surveillance.

During the coronavirus disease (COVID-19) pandemic, we admitted suspected or confirmed COVID-19 patients to our isolation wards between 2 March 2020 and 4 May 2020, following a well-designed and efficient assessment protocol. We included 217 patients suspected of COVID-19, of which 27 had confirmed COVID-19. The clinical characteristics of these patients were used to train artificial intelligence (AI) models such as support vector machine (SVM), decision tree, random forest, and artificial neural network for diagnosing COVID-19. When analyzing the performance of the models, SVM showed the highest sensitivity (SVM vs. decision tree vs. random forest vs. artificial neural network: 100% vs. 42.86% vs. 28.57% vs. 71.43%), while decision tree and random forest had the highest specificity (SVM vs. decision tree vs. random forest vs. artificial neural network: 88.37% vs. 100% vs. 100% vs. 94.74%) in the diagnosis of COVID-19. With the aid of AI models, physicians may identify COVID-19 patients earlier, even with few baseline data available, and segregate infected patients earlier to avoid hospital cluster infections and to ensure the safety of medical professionals and ordinary patients in the hospital.

Mercury speciation and mass distribution of coal-fired power plants in Taiwan using different air pollution control processes.

In this study, the mercury (Hg) emission, speciation, and mass distribution of four coal-fired power plants (CFPPs) located at central, southern, and northern Taiwan with various types of air pollution control devices were investigated. Gaseous Hg in the coal-combustion flue gas was sampled by using the Ontario Hydro method, and the solid and liquid samples were collected for understanding the Hg mass balance. The experimental results showed that the total Hg concentrations in flue gases at the inlets of selective catalytic reduction (SCR) varied from 2.984 to 4.692 µg Nm-3, while the total Hg concentrations in the flue gases at the stacks ranged from 0.240 to 0.675 µg Nm-3. These four CFPPs showed similar Hg speciation results at the stacks. The average Hg removal efficiencies of Plants 1 (SCR + electrostatic precipitator [ESP] + wet flue gas desulfurization [WFGD]), 2 (SCR + ESP + WFGD), 3 (SCR + bag filter (BF) + seawater flue gas desulfurization [SWFGD]) and 4 (SCR + BF + SWFGD) were 92.4%, 90.1%, 85.9%, and 84.8%, respectively. Coal was the major raw material in Hg input of CFPPs with a mass flow rate ranging 5.87-12.05 g hr-1. Elemental Hg (Hg0), accounting for 66.4%-97.1% of the total Hg, was the dominant species emitted to the atmosphere. The Hg mass balances for the four CFPPs varied from 86.0% to 117% of the Hg input, suggesting that good mass balances were obtained from the tested CFPPs.Implications: Mercury emissions from coal-fired power plant (CFPPs) have been greatly concerned and should thus be better comprehended. The present study examined the mercury speciation and mass distribution of four CFPPs located at Taiwan. Overall, these CFPPs had similar Hg speciation results at stack and Hg0 was the dominant species emitted to the atmosphere. The selective catalytic reduction (SCR) + electrostatic precipitator (ESP) + wet flue gas desulfurization (WFGD) system had the highest Hg removal efficiency and the Hg mass balances for the four CFPPs varied from 86.0 to 117%. This study helps better understanding the Hg emission inventory of CFPPs and provides useful information for selecting adequate air pollution control devices (APCDs) for Hg control.

Effects of low-frequency noise from wind turbines on heart rate variability in healthy individuals.

Wind turbines generate low-frequency noise (LFN, 20-200 Hz), which poses health risks to nearby residents. This study aimed to assess heart rate variability (HRV) responses to LFN exposure and to evaluate the LFN exposure (dB, LAeq) inside households located near wind turbines. Thirty subjects living within a 500 m radius of wind turbines were recruited. The field campaigns for LFN (LAeq) and HRV monitoring were carried out in July and December 2018. A generalized additive mixed model was employed to evaluate the relationship between HRV changes and LFN. The results suggested that the standard deviations of all the normal to normal R-R intervals were reduced significantly, by 3.39%, with a 95% CI = (0.15%, 6.52%) per 7.86 dB (LAeq) of LFN in the exposure range of 38.2-57.1 dB (LAeq). The indoor LFN exposure (LAeq) ranged between 30.7 and 43.4 dB (LAeq) at a distance of 124-330 m from wind turbines. Moreover, households built with concrete and equipped with airtight windows showed the highest LFN difference of 13.7 dB between indoors and outdoors. In view of the adverse health impacts of LFN exposure, there should be regulations on the requisite distances of wind turbines from residential communities for health protection.

An Integrated Platform for Serological Detection and Vaccination of COVID-19.

Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is an ongoing pandemic. Detection and vaccination are essential for disease control, but they are distinct and complex operations that require significant improvements. Here, we developed an integrated detection and vaccination system to greatly simplify these efforts. We constructed recombinant baculoviruses to separately display the nucleocapsid (N) and spike (S) proteins of SARS-CoV-2. Insect cells infected by the recombinant baculoviruses were used to generate a cell-based system to accurately detect patient serum. Notably, although well-recognized by our newly developed detection system in which S-displaying insect cells acted as antigen, anti-S antibodies from many patients were barely detectable by Western blot, evidencing that COVID-19 patients primarily produce conformation-dependent anti-S antibodies. Furthermore, the same baculovirus constructs can display N (N-Bac) or S (S-Bac) on the baculovirus envelope and serve as vector vaccines. Animal experiments show that S-Bac or N-Bac immunization in mice elicited a strong and specific antibody response, and S-Bac in particular stimulated effective neutralizing antibodies without the need for adjuvant. Our integrated system maintains antigen conformation and membrane structure to facilitate serum detection and antibody stimulation. Thus, compared with currently available technologies, our system represents a simplified and efficient platform for better SARS-CoV-2 detection and vaccination.

Assessment of low-frequency noise from wind turbines under different weather conditions.

BACKGROUND: Low-frequency (20-200 Hz) noise (LFN) from wind turbines has received much public attention due to potential health concerns. This work tries to estimate the sound power level of wind turbines (L W,A (dB)) at 20-200 Hz, which are not provided by manufacturers but essential for estimating LFN exposure (L Aeq) of nearby residents. METHODS: L W,A at 20-200 Hz at three wind farms, each with a different brand of wind turbine (Brands A, B and C, respectively) were estimated using propagation model ISO 9613-2 under different weather conditions (rain, wind speed and wind direction) and validated with LFN monitoring data. The feasibility of using validated L W,A as inputs for ISO 9613-2 to simulate residents' exposure (L Aeq) to LFN were assessed considering interferences from rain, wind speed and wind directions. RESULTS: The average L W,A at 20-200 Hz ranged between 93.2 and 100.4 dB, 97.8 and 107.2 dB, and 96.5 and 110.4 dB for turbines of Brands A, B, and C, respectively, operating under wind speeds from 2 to 12 m/s. The L W,A at wind speed of 2-8 m/s increased on average by 1.4, 1.9 and 1.7 dB per 1 m/s increase for Brands A, B and C, respectively. The differences in modeled Leq obtained through the input of L W,A into the ISO 9613-2 model and the measured L Aeq for the three studied wind farms all fall within 1.5 dB. CONCLUSION: This study successfully determined and validated the L W,A of wind turbines of three brands, and subsequent residents' LFN exposure (with 1.5 dB difference) at three wind farms. Accurately obtaining LFN exposure will serve as the basis for assessing LFN exposure-health relationship. As wind power widely use worldwide, health impact should be assessed based on validated LFN exposure assessment.

Multicentre study of risk factors for mortality in patients with Acinetobacter bacteraemia receiving colistin treatment.

Colistin remains a last-line antibiotic for the treatment of infections by multidrug-resistant Acinetobacter species. However, mortality rates are high in patients with Acinetobacter infection receiving colistin treatment. This multicentre study evaluated whether colistin susceptibility, additional antimicrobial agents or other prognostic factors influenced the clinical outcomes of patients receiving colistin treatment for Acinetobacter bacteraemia. This retrospective study enrolled 122 adults receiving colistin for monomicrobial Acinetobacter bacteraemia at six medical centres in the ACTION Study Group over an 8-year period. Clinical information, antimicrobial susceptibility and colistin resistance determinants were analysed. The primary outcome measure was 14-day mortality. Among 122 patients, 18 and 104 were infected with colistin-resistant (ColR) isolates [minimum inhibitory concentration (MIC) ≥4 mg/L] and colistin-susceptible (ColS) isolates (MIC ≤2 mg/L), respectively. Patients infected with ColR and ColS isolates did not differ significantly with regard to Charlson comorbidity index, invasive procedures, sources of bacteraemia, disease severity and 14-day mortality rate (44.4% vs. 34.6%; P = 0.592). No specific additional antimicrobial agent was independently associated with higher or lower mortality. Coronary artery disease, higher Acute Physiology and Chronic Health Evaluation (APACHE) II score and bacteraemia caused Acinetobacter baumannii were independent risk factors associated with 14-day mortality. Mechanisms of colistin resistance were associated with amino acid variants in the pmrCAB operon. Finally, previously unreported Acinetobacter nosocomialis amino acid variants related to colistin resistance were identified. In conclusion, colistin susceptibility and colistin combination antimicrobial treatment were not associated with decreased 14-day mortality in patients with Acinetobacter bacteraemia receiving colistin treatment.