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.

[Prognostic nutritional index application value for acute-on-chronic liver failure co-infection].

Objective: To explore the predictive value of the prognostic nutritional index (PNI) in concurrently infected patients with acute-on-chronic liver failure (ACLF). Methods: 220 cases with ACLF diagnosed and treated at the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2016 were selected. Patients were divided into an infection and non-infection group according to whether they had co-infections during the course of the disease. Clinical data differences were compared between the two groups of patients. Binary logistic regression analysis was used to screen out influencing factors related to co-infection. The receiver operating characteristic curve was used to evaluate the predictive value of PNI for ACLF co-infection. The measurement data between groups were compared using the independent sample t-test and the Mann-Whitney U rank sum test. The enumeration data were analyzed using the Fisher exact probability test or the Pearson χ(2) test. The Pearson method was performed for correlation analysis. The independent risk factors for liver failure associated with co-infection were analyzed by multivariate logistic analysis. Results: There were statistically significant differences in ascites, hepatorenal syndrome, PNI score, and albumin between the infection and the non-infection group (P < 0.05). Among the 220 ACLF cases, 158 (71.82%) were infected with the hepatitis B virus (HBV). The incidence rate of infection during hospitalization was 69.09% (152/220). The common sites of infection were intraabdominal (57.07%) and pulmonary infection (29.29%). Pearson correlation analysis showed that PNI and MELD-Na were negatively correlated (r = -0.150, P < 0.05). Multivariate logistic analysis results showed that low PNI score (OR=0.916, 95%CI: 0.865~0.970), ascites (OR=4.243, 95%CI: 2.237~8.047), and hepatorenal syndrome (OR=4.082, 95%CI : 1.106~15.067) were risk factors for ACLF co-infection (P < 0.05). The ROC results showed that the PNI curve area (0.648) was higher than the MELD-Na score curve area (0.610, P < 0.05). The effectiveness of predicting infection risk when PNI was combined with ascites and hepatorenal syndrome complications was raised. Patients with co-infections had a good predictive effect when PNI ≤ 40.625. The sensitivity and specificity were 84.2% and 41.2%, respectively. Conclusion: Low PNI score and ACLF co-infection have a close correlation. Therefore, PNI has a certain appraisal value for ACLF co-infection.

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.

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.

Bacterial and fungal secondary infections occurring in COVID-19 patients followed in intensive care: a retrospective study.

INTRODUCTION: We aimed to investigate the effects of secondary bacterial and fungal infections on patient outcomes in patients followed up in the intensive care unit (ICU) due to coronavirus disease 2019 (COVID-19). METHODOLOGY: We retrospectively analyzed reverse transcriptase polymerase chain reaction (RT-PCR) positive COVID-19 patients followed in the ICU of our hospital between March 2020 and June 2021, using the hospital information system. Demographic data, pathogens causing a secondary infection, onset time of secondary infection, and patient outcomes were recorded. RESULTS: A total of 251 RT-PCR positive patients who met the inclusion criteria were evaluated. The mean length of stay (LOS) in the ICU was 13.3 ± 9.6 days. During this period, 165 (65.7%) patients died. When blood, urine, respiratory tract, and catheter cultures were examined, the number of patients with growth in at least one culture was 129 (51.4%). There was growth in a total of 227 cultures. The highest culture positivity rate was observed in respiratory tract samples (n = 94, 41.4%). Gram-negative bacterial pathogens (n = 130, 58.4%) predominated. Candida spp. was more frequent in urine cultures. The median day of the occurrence of secondary infection was 10 (range: 6-15). Patients who developed secondary infection had a longer LOS and higher mortality rate than patients who did not (p < 0.001). CONCLUSIONS: Gram-negative secondary infections, predominantly in respiratory tract cultures, occurred in COVID-19 patients followed in the ICU. As a result, the LOS was prolonged and mortality rates increased.

Screening for Chlamydia and Gonorrhea in Youth Correctional Facilities, Utah, USA.

We reviewed data obtained in October 2021-May 2023 from youth who reported a history of sexual activity upon admission to 1 of 12 juvenile justice facilities in Utah, USA, that offered screening for Chlamydia trachomatis and Neisseria gonorrhoeae. Urinalysis revealed C. trachomatis positivity of 10.77%, N. gonorrhoeae positivity of 1.08%, and coinfection C. trachomatis N. gonorrhoeae) of 0.90%. Prevalence of infection was similar for youths in rural and urban facilities. A total of 12.01% of those identifying as male and 14.01% of those identifying as female tested positive for C. trachomatis, N. gonorrhoeae, or coinfection. Of young adults who tested positive, 74.65% received their results while incarcerated, all of whom accepted treatment. Our research underscores the feasibility of providing prompt C. trachomatis/N. gonorrhoeae screening and treatment in juvenile correctional facilities. The pervasiveness of infection emphasizes the urgent need for early identification and treatment for C. trachomatis and N. gonorrhoeae in incarcerated youth nationwide.

Assessment and clinical utility of metagenomic next-generation sequencing for suspected lower respiratory tract infections.

OBJECTIVES: This study aims to compare the diagnostic efficacy of metagenomic next-generation sequencing (mNGS) to traditional diagnostic methods in patients with lower respiratory tract infections (LRTIs), elucidate the etiological spectrum of these infections, and explore the impact of mNGS on guiding antimicrobial therapy. METHODS: We retrospectively analyzed data from 128 patients admitted to the Respiratory Department of Anqing 116 Hospital between July 2022 and July 2023. All patients had undergone both mNGS and conventional microbiological techniques (CMT) for LRTI diagnosis. We assessed the diagnostic performance of these methods and examined the influence of mNGS on antimicrobial decision-making. RESULTS: Overall, mNGS demonstrated superior sensitivity (96.8%) and accuracy (96.8%) compared to CMT. For Mycobacterium tuberculosis detection, the accuracy and sensitivity of mNGS was 88.8% and 77.6%, which was lower than the 94.7% sensitivity of the T-spot test and the 79.6% sensitivity of CMT. In fungal pathogen detection, mNGS showed excellent sensitivity (90.5%), specificity (86.7%), and accuracy (88.0%). Bacteria were the predominant pathogens detected (75.34%), with Mycobacterium tuberculosis (41.74%), Streptococcus pneumoniae (21.74%), and Haemophilus influenzae (16.52%) being most prevalent. Bacterial infections were most common (62.10%), followed by fungal and mixed infections (17.74%). Of the 118 patients whose treatment regimens were adjusted based on mNGS results, 102 (86.5%) improved, 7 (5.9%) did not respond favorably, and follow-up was lost for 9 patients (7.6%). CONCLUSIONS: mNGS offers rapid and precise pathogen detection for patients with suspected LRTIs and shows considerable promise in diagnosing Mycobacterium tuberculosis and fungal infections. By broadening the pathogen spectrum and identifying polymicrobial infections, mNGS can significantly inform and refine antibiotic therapy.

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.

Multiplex PCR in Diagnosing Respiratory Tract Infections in Hospitalized Children.

OBJECTIVES: To elaborate the utility of multiplex quantitative polymerase chain reaction (multiplex qPCR) for the accurate diagnosis of severe respiratory tract infections (RTIs) in hospitalized children. METHODS: In two separate periods during 2022, 76 respiratory specimens (combined throat/nasopharyngeal swabs) were submitted for multiplex qPCR regarding 26 respiratory pathogens. The specimens were obtained from children with severe RTIs hospitalized in the Institute for Respiratory Diseases in Children, Skopje. RESULTS: Multiplex qPCR detected at least one respiratory pathogen in all examined specimens (76/76), with 83% (63/76) rate of co-infections. Considering that positive results are only the ones with Ct value below 28, the rates of detected pathogens and co-infections decrease to 75% and 22%, respectively. The most commonly detected pathogens during the spring period were Parainfluenza type 3 (PIV3) followed by Adenovirus (AdV) and Respiratory syncytial virus type B (RSVB) with frequency rate of 23%, 19% and 19%, respectively. During the autumn period, the most common were RSVB and Streptococcus pneumoniae with frequency rate of 31% and 17%, respectively. CONCLUSION: Multiplex qPCR is a powerful tool for diagnosing RTIs. Semi-quantification of the viral load by reporting Ct values added higher level of evidence for accurate diagnosis. Seasonal detection of the examined viruses was notable with higher prevalence of PIV3 in spring and RSVB in autumn period.

Concurrent management of HIV and malaria: A comprehensive review of strategies to enhance quality of life.

The co-occurrence of human immunodeficiency virus and malaria presents a complex medical scenario, significantly impacting the quality of life for affected individuals. This comprehensive review synthesizes current knowledge, challenges, and strategies concerning the concurrent management of these infections to improve overall well-being. Epidemiological insights reveal the prevalence and demographic trends, highlighting geographical areas of concern and socioeconomic factors contributing to the burden of co-infection. Pathophysiological interactions elucidate the compounding effects, altering disease progression and treatment outcomes. Healthcare challenges underscore the necessity for integrated care models, evaluating existing healthcare frameworks and their efficacy in addressing dual infections. In-depth analysis of interventions explores pharmacological, behavioral, and preventive measures, evaluating their efficacy and safety in co-infected individuals. Additionally, the review assesses psychosocial support mechanisms, emphasizing community-based interventions and peer networks in enhancing holistic care. Consideration is given to the role of antiretroviral therapy, malaria prevention strategies, and the evolving landscape of healthcare delivery in optimizing outcomes for this vulnerable population. The paper concludes by emphasizing the significance of multidisciplinary approaches and integrated care models, stressing the need for continued research and collaborative efforts to advance interventions and improve the quality of life for those navigating the complexities of human immunodeficiency virus and malaria co-infection.

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.

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.

Adhesion of Klebsiella oxytoca to bladder or lung epithelial cells is promoted by the presence of other opportunistic pathogens.

The intestinal and respiratory tracts of healthy individuals serve as habitats for a diverse array of microorganisms, among which Klebsiella oxytoca holds significance as a causative agent in numerous community- and hospital-acquired infections, often manifesting in polymicrobial contexts. In specific circumstances, K. oxytoca, alongside other constituents of the gut microbiota, undergoes translocation to distinct physiological niches. In these new environments, it engages in close interactions with other microbial community members. As this interaction may progress to co-infection where the virulence of involved pathogens may be promoted and enhance disease severity, we investigated how K. oxytoca affects the adhesion of commonly co-isolated bacteria and vice versa during co-incubation of different biotic and abiotic surfaces. Co-incubation was beneficial for the adhesion of at least one of the two co-cultured strains. K. oxytoca enhanced the adhesion of other enterobacteria strains to polystyrene and adhered more efficiently to bladder or lung epithelial cell lines in the presence of most enterobacteria strains and S. aureus. This effect was accompanied by bacterial coaggregation mediated by carbohydrate-protein interactions occurring between bacteria. These interactions occur only in sessile, but not planktonic populations, and depend on the features of the surface. The data are of particular importance for the risk assessment of the urinary and respiratory tract infections caused by K. oxytoca, including those device-associated. In this paper, we present the first report on K. oxytoca ability to acquire increased adhesive capacities on epithelial cells through interactions with common causal agents of urinary and respiratory tract infections.

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.

Case report: A rare case of skin abscess caused by coinfection of Actinobaculum schaalii and Actinomyces turicensis.

Skin abscess is one of the most common infections of the skin and soft tissues. However, anaerobic bacteria are infrequently identified as the causative agents of this particular form of abscess. In this case, a 34-year-old pregnant woman was diagnosed with a skin abscess with the use of ultrasonography. The microbiological analysis results of the purulent fluid revealed the coinfection of Actinobaculum schaalii and Actinomyces turicensis. The patient was first treated empirically with 3 days of cefathiamidine, which resulted in no symptom improvement. Subsequently, a surgical procedure involving incision and draining was performed, with the administration of ceftriaxone. After 7 days of antibiotic intervention, the patient exhibited a satisfactory recovery. Clinicians need to be aware of other types of infections that might be attributed to Actinobaculum schaalii and Actinomyces turicensis, in addition to urinary tract infections.

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.

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.