Clinical outcomes of liver transplantation in human immunodeficiency virus/hepatitis B virus coinfected patients in China.

BACKGROUND: Highly active antiretroviral therapy (HAART) has been able to improve the immune system function and survival of human immunodeficiency virus (HIV) patients. However, Patients coinfected with HIV and hepatitis B virus (HBV) are more likely to develop end-stage liver disease (ESLD) than those infected with HBV alone. Consequently, liver transplantation is often required for these patients. This study evaluates the outcomes of orthotopic liver transplantation (OLT) of HIV-HBV coinfected patients in China. METHODS: We conducted a retrospective analysis on all HIV-HBV coinfected patients that underwent OLT from April 1, 2019 to December 31, 2021 and their outcomes were compared to all HBV monoinfected patients undergoing OLT during the same period. Patient outcomes were determined, including cumulative survival, viral load, CD4 T-cell count and postoperative complications. RESULTS: The median follow-up of HIV recipients was 36 months after OLT (interquartile range 12-39 months). Almost all patients had stable CD4 T-cell count (> 200 copies/ul), undetectable HBV DNA levels, and undetectable HIV RNA load during follow-up. The 1-, 2-, and 3-year posttransplant survival rates were 85.7% for the HIV group (unchanged from 1 to 3 years) versus 82.2%, 81.2%, and 78.8% for the non-HIV group. Cumulative survival among HIV-HBV coinfected recipients was not significantly different from the HBV monoinfected recipients (log-rank test P = 0.692). The percentage of deaths attributed to infection was comparable between the HIV and non-HIV groups (14.3% vs. 9.32%, P = 0.665). Post OLT, there was no significant difference in acute rejection, cytomegalovirus infection, bacteremia, pulmonary infection, acute kidney injury, de novo tumor and vascular and biliary complications. CONCLUSIONS: Liver transplantation in patients with HIV-HBV coinfection yields excellent outcomes in terms of intermediate- or long-term survival rate and low incidence of postoperative complications in China. These findings suggest that OLT is safe and feasible for HIV-HBV coinfected patients with ESLD. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2300067631), registered 11 January 2023.

Rescue of Mycobacterium bovis DNA Obtained from Cultured Samples during Official Surveillance of Animal TB: Key Steps for Robust Whole Genome Sequence Data Generation.

Epidemiological surveillance of animal tuberculosis (TB) based on whole genome sequencing (WGS) of Mycobacterium bovis has recently gained track due to its high resolution to identify infection sources, characterize the pathogen population structure, and facilitate contact tracing. However, the workflow from bacterial isolation to sequence data analysis has several technical challenges that may severely impact the power to understand the epidemiological scenario and inform outbreak response. While trying to use archived DNA from cultured samples obtained during routine official surveillance of animal TB in Portugal, we struggled against three major challenges: the low amount of M. bovis DNA obtained from routinely processed animal samples; the lack of purity of M. bovis DNA, i.e., high levels of contamination with DNA from other organisms; and the co-occurrence of more than one M. bovis strain per sample (within-host mixed infection). The loss of isolated genomes generates missed links in transmission chain reconstruction, hampering the biological and epidemiological interpretation of data as a whole. Upon identification of these challenges, we implemented an integrated solution framework based on whole genome amplification and a dedicated computational pipeline to minimize their effects and recover as many genomes as possible. With the approaches described herein, we were able to recover 62 out of 100 samples that would have otherwise been lost. Based on these results, we discuss adjustments that should be made in official and research laboratories to facilitate the sequential implementation of bacteriological culture, PCR, downstream genomics, and computational-based methods. All of this in a time frame supporting data-driven intervention.

Rationally designed probiotics prevent shrimp white feces syndrome via the probiotics-gut microbiome-immunity axis.

Increasing evidence infers that some complex diseases are attributed to co-infection with multiple pathogens, such as shrimp white feces syndrome (WFS); however, there is a lack of experimental evidence to validate such causal link. This deficiency further impedes rational design of probiotics to elicit desired benefits to shrimp WFS resistance. Herein, we validated the causal roles of Vibrio fluvialis, V. coralliilyticus and V. tubiashii (in a ratio of 7:2:1) in shrimp WFS etiology, which fully satisfied Koch's postulates. Correspondingly, we precisely designed four antagonistic strains: Ruegeria lacuscaerulensis, Nioella nitratireducens, Bacillus subtilis and Streptomyces euryhalinus in a ratio of 4:3:2:1, which efficiently guarded against WFS. Dietary supplementation of the probiotics stimulated beneficial gut populations, streptomycin, short chain fatty acids, taurine metabolism potentials, network stability, tight junction, and host selection, while reducing turnover rate and average variation degree of gut microbiota, thereby facilitating ecological and mechanical barriers against pathogens. Additionally, shrimp immune pathways, such as Fcγ R-mediated phagocytosis, Toll-like receptor and RIG-I-like receptor signaling pathways conferring immune barrier, were activated by probiotics supplementation. Collectively, we establish an updated framework for precisely validating co-infection with multiple pathogens and rationally designing antagonistic probiotics. Furthermore, our findings uncover the underlying beneficial mechanisms of designed probiotics from the probiotics-gut microbiome-host immunity axis.

An RNA-hydrolyzing recombinant minibody prevents both influenza A virus and coronavirus in co-infection models.

With the lifting of COVID-19 non-pharmaceutical interventions, the resurgence of common viral respiratory infections was recorded in several countries worldwide. It facilitates viral co-infection, further burdens the already over-stretched healthcare systems. Racing to find co-infection-associated efficacy therapeutic agents need to be rapidly established. However, it has encountered numerous challenges that necessitate careful investigation. Here, we introduce a potential recombinant minibody-associated treatment, 3D8 single chain variable fragment (scFv), which has been developed as a broad-spectrum antiviral drug that acts via its nucleic acid catalytic and cell penetration abilities. In this research, we demonstrated that 3D8 scFv exerted antiviral activity simultaneously against both influenza A viruses (IAVs) and coronaviruses in three established co-infection models comprising two types of coronaviruses [beta coronavirus-human coronavirus OC43 (hCoV-OC43) and alpha coronavirus-porcine epidemic diarrhea virus (PEDV)] in Vero E6 cells, two IAVs [A/Puerto Rico/8/1934 H1N1 (H1N1/PR8) and A/X-31 (H3N2/X-31)] in MDCK cells, and a combination of coronavirus and IAV (hCoV-OC43 and adapted-H1N1) in Vero E6 cells by a statistically significant reduction in viral gene expression, proteins level, and approximately around 85%, 65%, and 80% of the progeny of 'hCoV-OC43-PEDV', 'H1N1/PR8-H3N2/X-31', and 'hCoV-OC43-adapted-H1N1', respectively, were decimated in the presence of 3D8 scFv. Taken together, we propose that 3D8 scFv is a promising broad-spectrum drug for treatment against RNA viruses in co-infection.

Predictors of severe hepatotoxicity among retroviral infected adults on HAART regimen in Ilubabor Zone, Southwest Ethiopia.

Nearly half of the deaths among hospitalized human immuno deficiency virus-infected patients in the highly active antiretroviral therapy era have been attributed to liver disease. This may range from an asymptomatic mild increase of liver enzymes to cirrhosis and liver failure. Different works of literature elucidated both retroviral infection and the adverse effects of highly active antiretroviral therapy as a cause of hepatotoxicity. Individual adaptations to medications and environmental exposures, shaped by cultural norms and genetic predispositions, could potentially modulate the risk and progression of liver disease in this population. Therefore, this study aims to assess the predictors of severe hepatotoxicity in retroviral-infected adults receiving highly active antiretroviral therapy regimens within the Ilubabor Zone, Southwest Ethiopia. A facility-based cross-sectional study was conducted among adult retroviral-infected patients in five selected anti-retro virus therapy clinics from May1 to July 30/2022. A systematic sampling technique was used to select 457 study participants and Binary logistic regression statistical data analysis was used, P value < 0.05 was considered statistically significant. The prevalence of severe hepatotoxicity was 21.44% in the study population. CD+4 count < 200 cells/mm3 (AOR = 2.19, 95% CI 1.04-5.22, P = 0.01), human immunodeficiency virus co-infection with tuberculosis (AOR = 2.82, 95% CI 1.01-8.29, P = 0.03) and human immuno deficiency virus co-infection with hepatitis-B/hepatitis C virus (AOR = 5.02, 95% CI 1.82-16.41) were predictors of severe hepatotoxicity. The magnitude of severe hepatotoxicity was high among adult retroviral-infected patients on highly active anti-retroviral drug regimens. Co-infection of human immuno deficiency virus with hepatitis B virus or hepatitis C virus, tuberculosis and CD4+T-cell count below 200 cells/mm3 were predictors of severe hepatotoxicity. Therefore, HIV patients on highly active antiretroviral therapy require close attention and regular monitoring of their liver function.

Controlling Recombination to Evolve Bacteriophages.

Recombination among different phages sometimes facilitates their ability to grow on new hosts. Protocols to direct the evolution of phage host range, as might be used in the application of phage therapy, would then benefit from including steps to enable recombination. Applying mathematical and computational models, in addition to experiments using phages T3 and T7, we consider ways that a protocol may influence recombination levels. We first address coinfection, which is the first step to enabling recombination. The multiplicity of infection (MOI, the ratio of phage to cell concentration) is insufficient for predicting (co)infection levels. The force of infection (the rate at which cells are infected) is also critical but is more challenging to measure. Using both a high force of infection and high MOI (>1) for the different phages ensures high levels of coinfection. We also apply a four-genetic-locus model to study protocol effects on recombinant levels. Recombinants accumulate over multiple generations of phage growth, less so if one phage outgrows the other. Supplementing the phage pool with the low-fitness phage recovers some of this 'lost' recombination. Overall, fine tuning of phage recombination rates will not be practical with wild phages, but qualitative enhancement can be attained with some basic procedures.

Predictors of quality of life of TB/HIV co-infected patients in the Northern region of Ghana.

BACKGROUND: Tuberculosis (TB) and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) co-morbidity continues to be a serious worldwide health issue, particularly in Sub-Saharan Africa. Studies on the quality of life (QOL) of TB/HIV co-infected patients guide stakeholders on the delivery of patient-centred healthcare. This study evaluated QOL of TB/HIV co-infected individuals and its contributing factors. METHODS: We conducted a cross-sectional study among TB/HIV co-infected patients, receiving treatment at clinics in the Northern Region of Ghana. Simple random sampling technique was used to select 213 patients from 32 clinics. We gathered information on patients' QOL using the World Health Organization QOL-HIV BREF assessment tool. At a 5% level of significance, multiple logistic regression analyses were carried out to find correlates of QOL among the patients. RESULTS: The mean age of the patients was (38.99 ± 14.00) years with most, 33.3% (71/213) aged 30-39 years. Males constituted 54.9% (117/213). About 30.0% (64/213) of the patients reported a good QOL. Being employed (aOR = 5.23, 95% CI: 1.87 - 14.60), and adhering to treatment (aOR = 6.36, 95% CI: 1.51 - 26.65) were significantly associated with a good QOL. Being depressed (aOR = 0.02, 95% CI: 0.03 - 0.29), stigmatized (aOR = 0.31, 95% CI : 0.11 - 0.84), and not exercising (aOR = 0.28, 95% CI: 0.12 - 0.67) were negatively associated with a good QOL. CONCLUSION: Less than one-third of TB/HIV co-infected patients in the region have good QOL. To guarantee good QOL, modifiable predictors such as patients' physical activity and medication adherence should be targeted by the National AIDS and TB Control Programs.

Development and validation of machine learning-based models for predicting healthcare-associated bacterial/fungal infections among COVID-19 inpatients: a retrospective cohort study.

BACKGROUND: COVID-19 and bacterial/fungal coinfections have posed significant challenges to human health. However, there is a lack of good tools for predicting coinfection risk to aid clinical work. OBJECTIVE: We aimed to investigate the risk factors for bacterial/fungal coinfection among COVID-19 patients and to develop machine learning models to estimate the risk of coinfection. METHODS: In this retrospective cohort study, we enrolled adult inpatients confirmed with COVID-19 in a tertiary hospital between January 1 and July 31, 2023, in China and collected baseline information at admission. All the data were randomly divided into a training set and a testing set at a ratio of 7:3. We developed the generalized linear and random forest models for coinfections in the training set and assessed the performance of the models in the testing set. Decision curve analysis was performed to evaluate the clinical applicability. RESULTS: A total of 1244 patients were included in the training cohort with 62 healthcare-associated bacterial/fungal infections, while 534 were included in the testing cohort with 22 infections. We found that patients with comorbidities (diabetes, neurological disease) were at greater risk for coinfections than were those without comorbidities (OR = 2.78, 95%CI = 1.61-4.86; OR = 1.93, 95%CI = 1.11-3.35). An indwelling central venous catheter or urinary catheter was also associated with an increased risk (OR = 2.53, 95%CI = 1.39-4.64; OR = 2.28, 95%CI = 1.24-4.27) of coinfections. Patients with PCT > 0.5 ng/ml were 2.03 times (95%CI = 1.41-3.82) more likely to be infected. Interestingly, the risk of coinfection was also greater in patients with an IL-6 concentration < 10 pg/ml (OR = 1.69, 95%CI = 0.97-2.94). Patients with low baseline creatinine levels had a decreased risk of bacterial/fungal coinfections(OR = 0.40, 95%CI = 0.22-0.71). The generalized linear and random forest models demonstrated favorable receiver operating characteristic curves (ROC = 0.87, 95%CI = 0.80-0.94; ROC = 0.88, 95%CI = 0.82-0.93) with high accuracy, sensitivity and specificity of 0.86vs0.75, 0.82vs0.86, 0.87vs0.74, respectively. The corresponding calibration evaluation P statistics were 0.883 and 0.769. CONCLUSIONS: Our machine learning models achieved strong predictive ability and may be effective clinical decision-support tools for identifying COVID-19 patients at risk for bacterial/fungal coinfection and guiding antibiotic administration. The levels of cytokines, such as IL-6, may affect the status of bacterial/fungal coinfection.

Biased virus transmission following sequential coinfection of Aedes aegypti with dengue and Zika viruses.

BACKGROUND: Mosquito-borne arboviruses are expanding their territory and elevating their infection prevalence due to the rapid climate change, urbanization, and increased international travel and global trade. Various significant arboviruses, including the dengue virus, Zika virus, Chikungunya virus, and yellow fever virus, are all reliant on the same primary vector, Aedes aegypti. Consequently, the occurrence of arbovirus coinfection in mosquitoes is anticipated. Arbovirus coinfection in mosquitoes has two patterns: simultaneous and sequential. Numerous studies have demonstrated that simultaneous coinfection of arboviruses in mosquitoes is unlikely to exert mutual developmental influence on these viruses. However, the viruses' interplay within a mosquito after the sequential coinfection seems intricated and not well understood. METHODOLOGY/PRINCIPAL FINDINGS: We conducted experiments aimed at examining the phenomenon of arbovirus sequential coinfection in both mosquito cell line (C6/36) and A. aegypti, specifically focusing on dengue virus (DENV, serotype 2) and Zika virus (ZIKV). We firstly observed that DENV and ZIKV can sequentially infect mosquito C6/36 cell line, but the replication level of the subsequently infected ZIKV was significantly suppressed. Similarly, A. aegypti mosquitoes can be sequentially coinfected by these two arboviruses, regardless of the order of virus exposure. However, the replication, dissemination, and the transmission potential of the secondary virus were significantly inhibited. We preliminarily explored the underlying mechanisms, revealing that arbovirus-infected mosquitoes exhibited activated innate immunity, disrupted lipid metabolism, and enhanced RNAi pathway, leading to reduced susceptibility to the secondary arbovirus infections. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that, in contrast to simultaneous arbovirus coinfection in mosquitoes that can promote the transmission and co-circulation of these viruses, sequential coinfection appears to have limited influence on arbovirus transmission dynamics. However, it is important to note that more experimental investigations are needed to refine and expand upon this conclusion.

Bacterial and viral co-infections in aquaculture under climate warming: co-evolutionary implications, diagnosis, and treatment.

Climate change and the associated environmental temperature fluctuations are contributing to increases in the frequency and severity of disease outbreaks in both wild and farmed aquatic species. This has a significant impact on biodiversity and also puts global food production systems, such as aquaculture, at risk. Most infections are the result of complex interactions between multiple pathogens, and understanding these interactions and their co-evolutionary mechanisms is crucial for developing effective diagnosis and control strategies. In this review, we discuss current knowledge on bacteria-bacteria, virus-virus, and bacterial and viral co-infections in aquaculture as well as their co-evolution in the context of global warming. We also propose a framework and different novel methods (e.g. advanced molecular tools such as digital PCR and next-generation sequencing) to (1) precisely identify overlooked co-infections, (2) gain an understanding of the co-infection dynamics and mechanisms by knowing species interactions, and (3) facilitate the development multi-pathogen preventive measures such as polyvalent vaccines. As aquaculture disease outbreaks are forecasted to increase both due to the intensification of practices to meet the protein demand of the increasing global population and as a result of global warming, understanding and treating co-infections in aquatic species has important implications for global food security and the economy.

Clinical and immunologic features of co-infection in COVID-19 patients, along with potential traditional Chinese medicine treatments.

Objectives: With the increasing number of people worldwide infected with SARS-CoV-2, the likelihood of co-infection and/or comorbidities is rising. The impact of these co-infections on the patient's immune system remains unclear. This study aims to investigate the immunological characteristics of secondary infections in hospitalized COVID-19 patients, and preliminarily predict potential therapeutic effects of traditional Chinese medicine and their derivatives for the treatment of co-infections. Methods: In this retrospective cohort study, we included 131 hospitalized patients with laboratory-confirmed COVID-19, of whom there were 64 mild and 67 severe cases. We analyzed clinical characteristics and immunologic data, including circulating immune cell numbers, levels of inflammatory factors and viral load, comparing COVID-19 patients with and without co-infection. Results: Among 131 hospitalized COVID-19 patients, 41 (31.3%) were co-infection positive, with 33 (80.5%) having severe disease and 14 (34.1%) of them resulting in fatalities. Co-infected patients exhibited significantly higher severity and mortality rates compared to non-co-infected counterparts. Co-infected patients had significantly lower absolute counts of lymphocytes, total T lymphocytes, CD4+ T cells, CD8+ T cells and B lymphocytes, while levels of hs-CRP, PCT and IL-6 were significantly elevated compared to non-co-infected patients. Additionally, the viral load of co-infected patients was significantly higher than non-co-infected patients. Conclusion: Co-infection emerges as a dangerous factor for COVID-19 patients, elevating the risk of severe pneumonia and mortality. Co-infection suppresses the host's immune response by reducing the number of lymphocytes and increasing inflammation, thereby diminishing the antiviral and anti-infective effects of the immune system, which promotes the severity of the disease. Therefore, it is crucial to implement infection prevention measures to minimize the spread of co-infections among COVID-19 hospitalized patients. Additionally, changes in these biomarkers provide a theoretical basis for the effective treatment of co-infections with traditional Chinese medicine.

A new dynamic nomogram for predicting the risk of severe Mycoplasma pneumoniae pneumonia in children.

Mycoplasma pneumoniae pneumonia (MPP) is usually mild and self-limiting, but still about 12% of them will progress to severe Mycoplasma pneumoniae pneumonia (SMPP), which have poor survival rates and often require intensive medical resource utilization. We retrospectively collected clinical data from 526 children with MPP admitted to the Children's Hospital Affiliated to Zhengzhou University from June 2018 to February 2023 and randomly divided the data into a training cohort and a validation cohort at a ratio of 4:1. Univariate and multivariate logistic regressions were used to identify independent risk factors for SMPP. Age, AGR, NLR, CRP, ESR, MPV, coinfection, pleural effusion, primary disease, fever days ≥ 7 and wheeze are independent risk factors for SMPP in children. Then, we built an online dynamic nomogram ( https://ertongyiyuanliexiantu.shinyapps.io/SMPP/ ) based on the 11 independent risk factors. The C-index, ROC curve, DCA curve and calibration curve were used to assess the performance of the nomogram, which all showed that the dynamic nomogram has excellent clinical value. Based on age, AGR, NLR, CRP, ESR, MPV, coinfection, pleural effusion, primary disease, fever days ≥ 7 and wheeze, the first dynamic nomogram for accurately predicting SMPP was successfully established.

Cocirculation and coinfection of multiple respiratory viruses during autumn and winter seasons of 2023 in Beijing, China: A retrospective study.

China experienced severe epidemics of multiple respiratory pathogens in 2023 after lifting "Zero-COVID" policy. The present study aims to investigate the changing circulation and infection patterns of respiratory pathogens in 2023. The 160 436 laboratory results of influenza virus and respiratory syncytial virus (RSV) from February 2020 to December 2023, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from June 2020 to December 2023, Mycoplasma pneumoniae, adenovirus, and human rhinovirus from January 2023 to December 2023 were analyzed. We observed the alternating epidemics of SARS-CoV-2 and influenza A virus (IAV), as well as the out-of-season epidemic of RSV during the spring and summer of 2023. Cocirculation of multiple respiratory pathogens was observed during the autumn and winter of 2023. The susceptible age range of RSV in this winter epidemic (10.5, interquartile range [IQR]: 5-30) was significantly higher than previously (4, IQR: 3-34). The coinfection rate of IAV and RSV in this winter epidemic (0.695%) was significantly higher than that of the last cocirculation period (0.027%) (p < 0.001). Similar trend was also found in the coinfection of IAV and SARS-CoV-2. The present study observed the cocirculation of multiple respiratory pathogens, changing age range of susceptible population, and increasing coinfection rates during the autumn and winter of 2023, in Beijing, China.

Evaluation of haematological parameters in haemolytic anaemia caused by tick-borne pathogens in grazing cattle.

BACKGROUND: No tick-borne pathogens (TBPs) causing haemolytic anaemia in cattle have been reported, except Theileria orientalis and complete blood count (CBC) profile is the only haematological parameter to determine the severity of regenerative haemolytic anaemia. OBJECTIVES: To identify the causative agents of TBP-induced haemolytic anaemia and determine haematological parameters that indicate haemolytic anaemia in grazing cattle. METHODS: Eighty-two Korean indigenous cattle (Hanwoo) were divided into two groups: grazing (n = 67) and indoor (n = 15) groups. CBC and serum biochemistry were performed. PCR was conducted using whole blood-extracted DNA to investigate the prevalence of TBPs. RESULTS: TBP-induced haemolytic anaemia was observed in the grazing group. In grazing cattle, co-infection (43.3%, 29/67) was most frequently detected, followed by T. orientalis (37.6%, 25/67) and Anaplasma phagocytophilum infections (1.5%, 1/67). In indoor cattle, only co-infection (20%, 3/15) was identified. Grazing cattle exhibited regenerative haemolytic anaemia with marked monocytosis, mild neutropenia, and thrombocytopenia. According to grazing frequency, the 1st-time grazing group had more severe anaemia than the 2nd-time grazing group. Elevations in indirect bilirubin and L-lactate due to haemolytic anaemia were identified, and correlations with the respective markers were determined in co-infected grazing cattle. CONCLUSIONS: Quantitative evaluation of haematocrit, mean corpuscular volume, and reticulocytes (markers of regenerative haemolytic anaemia in cattle) was performed for the first time. Our results show that, in addition to T. orientalis, A. phagocytophilum is strongly associated with anaemia. The correlation between haemolytic anaemia severity and haematological parameters (indirect bilirubin, reticulocytes, and L-lactate) was confirmed.

Characterization of genes related to the efflux pump and porin in multidrug-resistant Escherichia coli strains isolated from patients with COVID-19 after secondary infection.

BACKGROUND: Escherichia coli (E. coli) is a multidrug resistant opportunistic pathogen that can cause secondary bacterial infections in patients with COVID-19. This study aimed to determine the antimicrobial resistance profile of E. coli as a secondary bacterial infection in patients with COVID-19 and to assess the prevalence and characterization of genes related to efflux pumps and porin. METHODS: A total of 50 nonduplicate E. coli isolates were collected as secondary bacterial infections in COVID-19 patients. The isolates were cultured from sputum samples. Confirmation and antibiotic susceptibility testing were conducted by Vitek 2. PCR was used to assess the prevalence of the efflux pump and porin-related genes in the isolates. The phenotypic and genotypic evolution of antibiotic resistance genes related to the efflux pump was evaluated. RESULTS: The E. coli isolates demonstrated high resistance to ampicillin (100%), cefixime (62%), cefepime (62%), amoxicillin-clavulanic acid (60%), cefuroxime (60%), and ceftriaxone (58%). The susceptibility of E. coli to ertapenem was greatest (92%), followed by imipenem (88%), meropenem (86%), tigecycline (80%), and levofloxacin (76%). Regarding efflux pump gene combinations, there was a significant association between the acrA gene and increased resistance to levofloxacin, between the acrB gene and decreased resistance to meropenem and increased resistance to levofloxacin, and between the ompF and ompC genes and increased resistance to gentamicin. CONCLUSIONS: The antibiotics ertapenem, imipenem, meropenem, tigecycline, and levofloxacin were effective against E. coli in patients with COVID-19. Genes encoding efflux pumps and porins, such as acrA, acrB, and outer membrane porins, were highly distributed among all the isolates. Efflux pump inhibitors could be alternative antibiotics for restoring tetracycline activity in E. coli isolates.

Metagenomic Next-Generation Sequencing Contributes to the Early Diagnosis of Mixed Infections in Central Nervous System.

Central nervous system (CNS) infections represent a challenge due to the complexities associated with their diagnosis and treatment, resulting in a high incidence rate and mortality. Here, we presented a case of CNS mixed infection involving Candida and human cytomegalovirus (HCMV), successfully diagnosed through macrogenomic next-generation sequencing (mNGS) in China. A comprehensive review and discussion of previously reported cases were also provided. Our study emphasizes the critical role of early pathogen identification facilitated by mNGS, underscoring its significance. Notably, the integration of mNGS with traditional methods significantly enhances the diagnostic accuracy of CNS infections. This integrated approach has the potential to provide valuable insights for clinical practice, facilitating early diagnosis, allowing for treatment adjustments, and ultimately, improving the prognosis for patients with CNS infections.

Clinical application of metagenomic next-generation sequencing for the diagnosis of suspected infection in adults: A cross-sectional study.

Metagenomic next-generation sequencing (mNGS) has become an available method for pathogen detection. The clinical application of mNGS requires further evaluation. We conducted a cross-sectional study of 104 patients with suspected infection between May 2019 and May 2021. The risk factors associated with infection were analyzed using univariate logistic analysis. The diagnostic performance of pathogens was compared between mNGS and conventional microbiological tests. About 104 patients were assigned into 3 groups: infected group (n = 69), noninfected group (n = 20), and unknown group (n = 15). With the composite reference standard (combined results of all microbiological tests, radiological testing results, and a summary of the hospital stay of the patient) as the gold standard, the sensitivity, specificity, positive predictive value, negative predictive value of mNGS was 84.9%, 50.0%, 88.6%, and 42.1%, respectively. Compared with conventional microbiological tests, mNGS could detect more pathogens and had obvious advantages in Mycobacterium tuberculosis, Aspergillus, and virus detection. Moreover, mNGS had distinct benefits in detecting mixed infections. Bacteria-fungi-virus mixed infections were the most common in patients with severe pneumonia. mNGS had a higher sensitivity than conventional microbiological tests, especially for M. tuberculosis, Aspergillus, viruses, and mixed infections. We suggest that mNGS should be used more frequently in the early diagnosis of pathogens in critically ill patients in the future.

Gut-Lung Microbiota Characterization in Patients with Non-Small Cell Lung Carcinoma and COVID-19 Coinfection.

BACKGROUND: Non-small cell lung cancer (NSCLC) patients with COVID-19 have an excessive chance of morbidity and mortality. The fecal-nasopharyngeal microbiota compositions of NSCLC patients were assessed in this study. METHODS: In total, 234 samples were collected from 17 NSCLC patients infected with COVID-19, 20 NSCLC patients without confirmed COVID-19, 40 non NSCLC patients with COVID-19, and 40 healthy individuals. RESULTS: In lung microbiota, the abundance of Streptococcus spp. in NSCLC patients with confirmed COVID-19 was significantly higher than the two control groups. Pseudomonas aeruginosa and Staphylococcus aureus were listed as the most frequent pulmonary bacterial groups that colonized COVID-19 patients. In fecal specimens, the numbers of Bacteroidetes, Firmicutes, and Actinobacteria phyla were significantly higher amongst NSCLC patients with COVID-19. NSCLC patients infected with COVID-19 showed lower levels of Lactobacillus spp., Akkermansia muciniphila, and Bifidobacterium spp. The counts of Streptococcus spp., in NSCLC patients with COVID-19 were significantly higher than those of healthy individuals (8.49±0.70 log CFU/g wet feces vs 8.49±0.70 log CFU/g wet feces). Prevotella spp. were enriched in the gut and respiratory tracts of COVID-19 patient groups. The unbiased analysis showed an increment in Enterococcus spp., Streptococcus spp., and Prevotella spp. CONCLUSION: Eventually, it was found that compared to control groups, COVID-19 patients with NSCLC showed diminished gut bacteria diversity and increase in Lactobacillus spp., A. muciniphila, and Bifidobacterium spp. The overgrowth of Enterococcus spp., Streptococcus spp., and Prevotella spp. could be potential predictive biomarkers in the gut-lung axis of NSCLC patients with COVID-19.

Deciphering the virome of Chunkung (Cnidium officinale) showing dwarfism-like symptoms via a high-throughput sequencing analysis.

BACKGROUND: Viruses have notable effects on agroecosystems, wherein they can adversely affect plant health and cause problems (e.g., increased biosecurity risks and economic losses). However, our knowledge of their diversity and interactions with specific host plants in ecosystems remains limited. To enhance our understanding of the roles that viruses play in agroecosystems, comprehensive analyses of the viromes of a wide range of plants are essential. High-throughput sequencing (HTS) techniques are useful for conducting impartial and unbiased investigations of plant viromes, ultimately forming a basis for generating further biological and ecological insights. This study was conducted to thoroughly characterize the viral community dynamics in individual plants. RESULTS: An HTS-based virome analysis in conjunction with proximity sampling and a tripartite network analysis were performed to investigate the viral diversity in chunkung (Cnidium officinale) plants. We identified 61 distinct chunkung plant-associated viruses (27 DNA and 34 RNA viruses) from 21 known genera and 6 unclassified genera in 14 known viral families. Notably, 12 persistent viruses (7 DNA and 5 RNA viruses) were exclusive to dwarfed chunkung plants. The detection of viruses from the families Partitiviridae, Picobirnaviridae, and Spinareoviridae only in the dwarfed plants suggested that they may contribute to the observed dwarfism. The co-infection of chunkung by multiple viruses is indicative of a dynamic and interactive viral ecosystem with significant sequence variability and evidence of recombination. CONCLUSIONS: We revealed the viral community involved in chunkung. Our findings suggest that chunkung serves as a significant reservoir for a variety of plant viruses. Moreover, the co-infection rate of individual plants was unexpectedly high. Future research will need to elucidate the mechanisms enabling several dozen viruses to co-exist in chunkung. Nevertheless, the important insights into the chunkung virome generated in this study may be relevant to developing effective plant viral disease management and control strategies.

Effect of concurrent infection of Helicobacter pylori with Toxoplasma gondii infection on gastric pathology.

BACKGROUND: Toxoplasma gondii (T. gondii) and Helicobacter pylori (H. pylori) are among the most prevalent foodborne parasitic and bacterial infections worldwide. However, the concurrent impact of coinfection on gastric pathology has yet to be studied in depth. The effect of coinfection generally either adds a synergetic or antagonistic impact; we aimed in the current work to assess the impact of T. gondii coinfection on the progression of H. pylori-associated gastric pathology and reporting H. pylori virulent strains. The study was conducted on 82 patients complaining of persistent gastrointestinal symptoms with failed treatment response and prone to endoscopy. They were subjected to stool examination to detect H. pylori antigen, serological screening for latent toxoplasmosis, endoscopy, histopathological examination, and molecular detection of H. pylori virulence strains in gastric biopsies. Out of the 82 patients, 62 patients were positive for H. pylori antigen in stool and 55 patients confirmed positivity by histopathology; out of them, 37 patients had isolated Vac As1 variants, 11 patients had combined Vac As1 and Cag A variants, and 7 patients had combined Vac As1, Cag A and VacAs2 variants. Patients with the combined two or three variances showed significantly deteriorated histopathological features than patients with a single Vac As1 variant (P < 0.05). Latent toxoplasmosis was positive among 35/82 patients. Combined H. pylori and Toxoplasma gondii infection had significantly marked inflammation than patients with isolated infection (P < 0.05). CONCLUSION: Screening for toxoplasmosis among H. pylori-infected patients is recommended as it is considered a potential risk factor for gastric inflammation severity. H. pylori gastric inflammation may be heightened by Toxoplasma coinfection.