COVID-19 Pandemic Modulates the Environmental Contamination Level with Enteric Bacteria from WWTPs (preprint)

The Covid-19 pandemic was a challenge for the whole world and it had major secondary effects on humans and environmental health. The viral infection induced, in many situations, secondary bacterial infections, especially enteric infections by destabilizing the balance of the gastrointestinal microbiota. The large-scale use of antibiotics and biocides both for curative and preventive purposes has determined an increase in bacterial resistance and at the same time the possibility of pathogenic microorganisms’ multiplication and their dissemination to natural environments. Wastewater is the main vector of faecal microorganisms that favour their dissemination into natural aquatic ecosystems. The present paper aimed to analyze the effect of Covid-19 pandemic on the microbiological quality of wastewater from sewage treatment plants in Romania and its impact on receiving rivers. In order to highlight different and important areas of Romania, 3 cities from the east, center and west were selected for a microbiological evaluation of their WWTPs influent and effluent between ante-Covid-19 and Covid-19 pandemic peak period, when the Covid-19 pandemic had a direct impact on WWTPs microbial composition. Our study showed a higher contamination with fecal bacteria linked to a higher Covid-19 incidence. The increased usage of pharmaceutical compounds, at their turn, increased the number of resistant bacteria reaching the environment via WWTP effluents.

Bayesian Sensor Placement for Multi-source Localization of Pathogens in Wastewater Networks (preprint)

Wastewater monitoring is an effective approach for the early detection of viral and bacterial disease outbreaks. It has recently been used to identify the presence of individuals infected with COVID-19. To monitor large communities and accurately localize buildings with infected individuals with a limited number of sensors, one must carefully choose the sampling locations in wastewater networks. We also have to account for concentration requirements on the collected wastewater samples to ensure reliable virus presence test results. We model this as a sensor placement problem. Although sensor placement for source localization arises in numerous problems, most approaches use application-specific heuristics and fail to consider multiple source scenarios. To address these limitations, we develop a novel approach that combines Bayesian networks and discrete optimization to efficiently identify informative sensor placements and accurately localize virus sources. Our approach also takes into account concentration requirements on wastewater samples during optimization. Our simulation experiments demonstrate the quality of our sensor placements and the accuracy of our source localization approach. Furthermore, we show the robustness of our approach to discrepancies between the virus outbreak model and the actual outbreak rates.

Tip of the Iceberg: A New Wave of Iron-Sulfur Cluster Proteins Found in Viruses (preprint)

Viruses rely on host cells to replicate their genomes and assemble new viral particles. Thus, they have evolved intricate mechanisms to exploit host factors. Host cells, in turn, have developed strategies to inhibit viruses, resulting in a nuanced interplay of co-evolution between virus and host. This dynamic often involves competition for resources crucial for both host cell survival and virus replication. Iron and iron-containing cofactors, including iron-sulfur clusters, are known to be a heavily battled resource during bacterial infections where control over iron can tug the war in favor of the pathogen or the host. It is logical to assume that viruses also engage in this competition. Surprisingly, our knowledge about how viruses utilize iron (Fe) and iron-sulfur (FeS) clusters remains limited. The handful of reviews on this topic primarily emphasize the significance of iron in supporting the host immune response against viral infections. The aim of this review, however, is to organize our current understanding of how viral proteins utilize FeS clusters, to give perspectives on what questions to ask next and to propose important avenues for future investigations.

RSV-bacterial co-infection is associated with increased illness severity in hospitalized children - Results from a prospective sentinel surveillance study (preprint)

Purpose: During the autumn/winter respiratory syncytial virus (RSV) epidemics, bacterial co-infection is common and affects the severity of the disease. We aimed to understand the relationship between RSV-bacterial co-infections and clinical severity since the change of RSV seasonality after the COVID-19 pandemic. Methods: We conducted a prospective, sentinel surveillance study at 20 sites in Portugal in children under two years old hospitalized with RSV, between April 2021 and January 2023. The effect of co-infection with potentially pathogenic bacteria (PPB) on the length of hospitalization and disease severity (defined by the need for ventilation or admission to an intensive care unit-ICU) was investigated using multivariate linear and log-binomial regression models. Age group (<6 months/≥6 months) and prematurity (yes/no) were included in models as potential confounders. Results: We report two RSV off-season epidemics: June 2021-February 2022 and May-October 2022. Among 678 RSV hospitalizations, 67.4 % occurred in children under 6 months old and 15.3 % in pre-term; 20.4 % tested positive for PPB; median length of hospitalization was five days (IQR: 3-7days); 5.8 % had at least one underlying condition. The most common bacteria were Haemophilus influenzae and Streptococcus pneumoniae. Children co-infected with PPB had a higher rate of ICU admission (29.7 % versus 3.5 %, p<0.001), resulting in more prolonged hospitalizations (median of 7 days versus 5 days, p<0.001) and a 13-fold risk of having severe disease (RR: 13.2, 95 CI: 7.3-23.9). Conclusion: RSV-bacterial co-infection was associated with increased length of hospitalization and severe illness during off-season epidemics. This risk is probably overestimated, as laboratory testing for bacterial infections is usually higher in severely ill-appearing children. Measures to prevent outgrowth of pathogenic bacteria within the respiratory tract should be discussed.

COVID-19 Caused by the Omicron Variant in Lung Transplant Recipients: A Single Center Case Series (preprint)

Background: Limited data from the Chinese experience are available regarding the infection status, clinical characteristics, treatments and early outcomes of lung transplant recipients (LTRs) afflicted with coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 Omicron Variant. Methods: We conducted a study on LTRs with COVID-19 caused by the Omicron Variant from November 17, 2022, to May 1, 2023. Clinical information was gathered through electronic medical records, questionnaires, or follow-up telephone calls. To identify potential risk factors for severe disease progression, a multivariate logistic analysis was performed. Results: 178 LTRs with COVID-19 were included, with 50% (89/178) requiring hospitalization for an average stay of 16 days (IQR: 9.5-25.5 days). The most common symptoms were fever (79.8%), dry cough (75.3%) and fatigue (61.8%). Ultimately, 17 recipients succumbed to COVID-19-related respiratory failure or secondary multiple organ dysfunction, resulting in an overall mortality rate of 9.6%. Of the 89 hospitalized patients, 41.6% (37/89) eventually progressed to severe or critical disease, forming the Severe/Critical Group (S/C group), while the remaining 58.4% (52/89) had mild to moderate disease (M/M group). In comparison to the M/M group, the S/C group had higher CRP (59.6 vs. 16.8 mg/L, P＜0.01), ESR (45.5 vs. 22.5mm/h, P＜0.01) and D-dimer (1.09 vs. 0.65 mg/L, P＜0.05), but lower CD3+ T lymphocytes (577 vs. 962 cells/ul, P＜0.01) and CD4+ T lymphocytes (217 vs. 427 cells/ul, P＜0.01). The S/C group had significantly higher rates of combined pulmonary bacterial infection (67.6% vs. 38.5%, P＜0.01) and pulmonary fungal infection (73.0% vs. 38.5%, P＜0.01) during the course of COVID-19, nearly double that of the M/M group. In a multivariate logistic analysis, elevated CRP (>41.8mg/L), combined pulmonary fungal infection, and interstitial lung disease(ILD) as primary disease emerged as high-risk factors for developing the severe disease phenotype following Omicron variant infection in LTRs, with respective OR values of 4.23 (95% CI: 1.68-11.23), 4.76 (95% CI: 1.59-15.64), and 5.13 (95% CI: 1.19-29.17). Conclusions: LTRs displayed an increased vulnerability to combined lung bacterial or fungal infections following Omicron infection. CRP> 41.8mg/L, ILD as primary disease, and combined pulmonary fungal infection are high-risk factors for developing severe disease.

Differentiation of COVID-19 from other emergency infectious disease presentations using whole blood transcriptomics then rapid qPCR: a case-control and observational cohort study (preprint)

Background. The overlapping clinical presentations of patients with acute respiratory disease can complicate disease diagnosis. Whilst PCR diagnostic methods to identify SARS-CoV-2 are highly sensitive, they have their shortcomings including false-positive risk and slow turnaround times. Changes in host gene expression can be used to distinguish between disease groups of interest, providing a viable alternative to infectious disease diagnosis. Methods. We interrogated the whole blood gene expression profiles of patients with COVID-19 (n=87), bacterial infections (n=88), viral infections (n=36), and not-infected controls (n=27) to identify a sparse diagnostic signature for distinguishing COVID-19 from other clinically similar infectious and non-infectious conditions. The sparse diagnostic signature underwent validation in a new cohort using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and then underwent further external validation in an independent in silico RNA-seq cohort. Findings. We identified a 10-gene signature (OASL, UBP1, IL1RN, ZNF684, ENTPD7, NFKBIE, CDKN1C, CD44, OTOF, MSR1) that distinguished COVID-19 from other infectious and non-infectious diseases with an AUC of 87.1% (95% CI: 82.6%-91.7%) in the discovery cohort and 88.7% and 93.6% when evaluated in the RT-qPCR validation, and in silico cohorts respectively. Interpretation. Using well-phenotyped samples collected from patients admitted acutely with a spectrum of infectious and non-infectious syndromes, we provide a detailed catalogue of blood gene expression at the time of hospital admission. The findings result in the identification of a 10-gene host diagnostic signature to accurately distinguish COVID-19 from other infection syndromes presenting to hospital. This could be developed into a rapid point-of-care diagnostic test, providing a valuable syndromic diagnostic tool for future early pandemic use.

Evaluation of the impact of COVID-19 pandemic on hospital admission related to common infections (preprint)

Background: Antimicrobial resistance (AMR) is a multifaceted global challenge, partly driven by inappropriate antibiotic prescribing. The COVID-19 pandemic impacted antibiotic prescribing for common bacterial infections. This highlights the need to examine risk of hospital admissions related to common infections, excluding COVID-19 infections during the pandemic. Methods: With the approval of NHS England, we accessed electronic health records from The Phoenix Partnership (TPP) through OpenSAFELY platform. We included patients with primary care diagnosis of common infections, including lower respiratory tract infection (LRTI), upper respiratory tract infections (URTI), and lower urinary tract infection (UTI), from January 2019 to August 2022. We excluded patients with a COVID-19 record 90 days before to 30 days after the infection diagnosis. Using Cox proportional-hazard regression models, we predicted risk of infection-related hospital admission in 30 days follow-up period after the diagnosis. Results: We found 12,745,165 infection diagnoses from January 2019 to August 2022. Of them, 80,395 (2.05%) cases were admitted to hospital in the follow-up period. Counts of hospital admission for infections dropped during COVID-19, e.g., LRTI from 3,950 in December 2019 to 520 in April 2020. Comparing those prescribed an antibiotic to those without, reduction in risk of hospital admission were largest with LRTI (adjusted odds ratio (OR) of 0.35; 95% CI, 0.35-0.36) and UTI (adjusted OR 0.45; 95% CI, 0.44-0.46), compared to URTI (adjusted OR 1.04; 95% CI, 1.03-1.06). Conclusion: Large effectiveness of antibiotics in preventing complications related to LRTI and UTI can support better targeting of antibiotics to patients with higher complication risks.

Unleashing the Power of Artificial Intelligence: Unraveling the Intricate Dynamics between Viral and Bacterial Infections, Immune Factors, COVID-19, and Cancer in Women's Health (preprint)

The intricate interplay between viral and bacterial infections, immune factors, COVID-19, and cancer in women's health has garnered significant attention in recent research. This comprehensive study aimed to unravel the complex dynamics between these factors and provide valuable insights into their implications for women's health. Through meticulous analysis of available data, this study elucidated the prevalence of viral and bacterial infections in women, encompassing influential pathogens such as influenza, human papillomavirus, Staphylococcus aureus, Escherichia coli, and Streptococcus pneumoniae. Additionally, it explored the relationship between specific cytokine types, including Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), Interferon-gamma (IFN-γ), and Interleukin-10 (IL-10), and viral infections. The prevalence of various cancer types, such as breast cancer, lung cancer, colorectal cancer, ovarian cancer, and cervical cancer, was also assessed. Furthermore, this study examined the correlations between immune factors and viral infections, uncovering significant associations that shed light on the intricate interplay between immune responses and viral infections. Immune markers such as IL-6, TNF-α, IFN-γ, Interleukin-1beta (IL-1β), and Interleukin-12 (IL-12) exhibited diverse levels of correlation with specific viral infections. These findings hold promise for disease prognosis and treatment optimization. Additionally, the association between bacterial infections and women's health conditions was explored, revealing the impact of pathogens like Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Enterococcus faecalis on gynecological infections, reproductive disorders, and other relevant conditions. This highlights the need for effective strategies to prevent and manage bacterial infections, aiming to mitigate their adverse effects on women's health. In the context of COVID-19, this study investigated immune factors as predictors of disease outcomes in women. Various cytokines, including IL-6, TNF-α, IL-1β, IFN-γ, IL-10, IL-8, IL-4, IL-2, IL-12, and IL-17, demonstrated associations with disease severity, offering potential prognostic markers for identifying individuals at higher risk of severe illness. Furthermore, the relationship between viral and bacterial infections and cancer incidence in women was explored. Viral infections, such as human papillomavirus and influenza, showed associations with specific cancer types, including breast cancer, cervical cancer, lung cancer, skin cancer, and stomach cancer. Bacterial infections, such as Staphylococcus aureus and Escherichia coli, were linked to ovarian cancer, colorectal cancer, pancreatic cancer, bladder cancer, kidney cancer, and esophageal cancer. These findings provide valuable insights into the potential role of infectious etiologies in cancer development among women. In conclusion, this comprehensive study unveils the intricate dynamics between viral and bacterial infections, immune factors, COVID-19, and cancer in women's health. The findings emphasize the importance of considering the interconnectedness of these factors to enhance disease prevention, diagnosis, and treatment strategies in women. Further research is warranted to unravel the underlying mechanisms and translate these findings into clinical applications.

Pre-existing interferon gamma conditions the lung to mediate early control of SARS-CoV-2 (preprint)

Interferons (IFNs) are critical for anti-viral host defence. Type-1 and type-3 IFNs are typically associated with early control of viral replication and promotion of inflammatory immune responses; however, less is known about the role of IFN{gamma} in anti-viral immunity, particularly in the context of SARS-CoV-2. We have previously observed that lung infection with attenuated bacteria Mycobacterium bovis BCG achieved though intravenous (iv) administration provides strong protection against SARS-CoV-2 (SCV2) infection and disease in two mouse models. Assessment of the pulmonary cytokine milieu revealed that iv BCG induces a robust IFN{gamma} response and low levels of IFN{beta}. Here we examined the role of ongoing IFN{gamma} responses due to pre-established bacterial infection on SCV2 disease outcomes in two murine models. We report that IFN{gamma} is required for iv BCG induced reduction in pulmonary viral loads and that this outcome is dependent on IFN{gamma} receptor expression by non-hematopoietic cells. Further analysis revealed that BCG infection promotes the upregulation of interferon-stimulated genes (ISGs) with reported anti-viral activity by pneumocytes and bronchial epithelial cells in an IFN{gamma}-dependent manner, suggesting a possible mechanism for the observed protection. Finally, we confirmed the importance of IFN{gamma} in these anti-viral effects by demonstrating that the recombinant cytokine itself provides strong protection against SCV2 challenge when administered intranasally. Together, our data show that a pre-established IFN{gamma} response within the lung is protective against SCV2 infection, suggesting that concurrent or recent infections that drive IFN{gamma} may limit the pathogenesis of SCV2 and supporting possible prophylactic uses of IFN{gamma} in COVID-19 management.

Biomarker-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection: statistical analysis plan for the BATCH trial and PRECISE sub-study.

INTRODUCTION: The BATCH trial is a multi-centre randomised controlled trial to compare procalcitonin-guided management of severe bacterial infection in children with current management. PRECISE is a mechanistic sub-study embedded into the BATCH trial. This paper describes the statistical analysis plan for the BATCH trial and PRECISE sub-study. METHODS: The BATCH trial will assess the effectiveness of an additional procalcitonin test in children (aged 72 h to 18 years) hospitalised with suspected or confirmed bacterial infection to guide antimicrobial prescribing decisions. Participants will be enrolled in the trial from randomisation until day 28 follow-up. The co-primary outcomes are duration of intravenous antibiotic use and a composite safety outcome. Target sample size is 1942 patients, based on detecting a 1-day reduction in intravenous antibiotic use (90% power, two-sided) and on a non-inferiority margin of 5% risk difference in the composite safety outcome (90% power, one-sided), while allowing for up to 10% loss to follow-up. RESULTS: Baseline characteristics will be summarised overall, by trial arm, and by whether patients were recruited before or after the pause in recruitment due to the COVID-19 pandemic. In the primary analysis, duration of intravenous antibiotic use will be tested for superiority using Cox regression, and the composite safety outcome will be tested for non-inferiority using logistic regression. The intervention will be judged successful if it reduces the duration of intravenous antibiotic use without compromising safety. Secondary analyses will include sensitivity analyses, pre-specified subgroup analyses, and analysis of secondary outcomes. Two sub-studies, including PRECISE, involve additional pre-specified subgroup analyses. All analyses will be adjusted for the balancing factors used in the randomisation, namely centre and patient age. CONCLUSION: We describe the statistical analysis plan for the BATCH trial and PRECISE sub-study, including definitions of clinical outcomes, reporting guidelines, statistical principles, and analysis methods. The trial uses a design with co-primary superiority and non-inferiority endpoints. The analysis plan has been written prior to the completion of follow-up. TRIAL REGISTRATION: BATCH: ISRCTN11369832, registered 20 September 2017, doi.org/10.1186/ISRCTN11369832. PRECISE: ISRCTN14945050, registered 17 December 2020, doi.org/10.1186/ISRCTN14945050.

Monoclonal antibodies for prophylaxis and therapy of respiratory syncytial virus, SARS-CoV-2, human immunodeficiency virus, rabies and bacterial infections: an update from the World Association of Infectious Diseases and Immunological Disorders and the Italian Society of Antinfective Therapy.

Monoclonal antibodies (mABs) are safe and effective proteins produced in laboratory that may be used to target a single epitope of a highly conserved protein of a virus or a bacterial pathogen. For this purpose, the epitope is selected among those that play the major role as targets for prevention of infection or tissue damage. In this paper, characteristics of the most important mABs that have been licensed and used or are in advanced stages of development for use in prophylaxis and therapy of infectious diseases are discussed. We showed that a great number of mABs effective against virus or bacterial infections have been developed, although only in a small number of cases these are licensed for use in clinical practice and have reached the market. Although some examples of therapeutic efficacy have been shown, not unlike more traditional antiviral or antibacterial treatments, their efficacy is significantly greater in prophylaxis or early post-exposure treatment. Although in many cases the use of vaccines is more effective and cost-effective than that of mABs, for many infectious diseases no vaccines have yet been developed and licensed. Furthermore, in emergency situations, like in epidemics or pandemics, the availability of mABs can be an attractive adjunct to our armament to reduce the impact. Finally, the availability of mABs against bacteria can be an important alternative, when multidrug-resistant strains are involved.

Bacterial complications in patients with coronavirus infection, new diagnostic and therapeutic possibilities.

We present the case of a young patient who developed pneumonia during the COVID-19 outbreak. The course of the disease with involvement of interstitial lung tissue atypical for bacterial infections, the picture of infection markers could indicate SARS-CoV-2. The patient was tested by PCR method on admission with negative results. Due to the atypical follow-up of the disease, suggesting a severe course of SARS, PCR testing of the material collected by BAL was performed BIOFIRE® FILMARRAY® Pneumonia plus Panel (bioMérieux). Legionella pneumophilla and coronavirus genetic materials were found. We conclude that in the described case there was a bacterial co-infection, paved by virus infection. The similar radiological picture of the two cases of pneumonia, as well as the similar infectious response in the blood, specific for atypical infections, may pose a problem in the differential diagnosis. The study was able to confirm the bacterial etiology of pneumonia and introduce targeted treatment. The patient was discharged from the hospital. We believe that in any case of pneumonia of non-bacterial etiology, extending the diagnosis with a PCR pulmonary panel allows early and effective treatment of patients. In the treatment of patients with pulmonary interstitial lesions in the course of virus infections, one should always keep in mind the possibility of atypical co-infections.

Unveiling the dynamics of antimicrobial utilization and resistance in a large hospital network over five years: Insights from health record data analysis (preprint)

Background: Antimicrobial Resistance (AMR) presents a pressing public health challenge globally which has been compounded by the COVID-19 pandemic. Elucidation of the impact of the pandemic on AMR evolution using population-level data that integrates clinical, laboratory and prescription data remains lacking. Methods: Data was extracted from the centralized electronic platform which captures the health records of 60,551 patients across the network of public healthcare facilities in Dubai, United Arab Emirates. For all inpatients and outpatients diagnosed with bacterial infection between 01/01/2017 and 31/05/2022, structured and unstructured Electronic Health Record data, microbiological laboratory data including antibiogram, molecular typing and COVID-19 testing information as well as antibiotic prescribing data were extracted curated and linked. Various analytical methods, including time-series analysis, natural language processing (NLP) and unsupervised clustering algorithms, were employed to investigate the trends of antimicrobial usage and resistance over time, assess the impact of prescription practices on resistance rates, and explore the effects of COVID-19 on antimicrobial usage and resistance. Results: Our findings identified a significant impact of COVID-19 on antimicrobial prescription practices, with short-term and long-lasting over-prescription of these drugs. Resistance to antimicrobials increased the odds ratio of mortality to an average of 2.5 and the effects of prescription practices on resistance were observed within one week of initiation. Significant trends in antimicrobial resistance, exhibiting fluctuations for various drugs and organisms, with an overall increasing trend in resistance levels, particularly post-COVI D-19 were identified. Conclusion: This study provides a population-level insight into the evolution of AMR in the context of COVID-19 pandemic. The findings emphasize the long-term effect of COVID-19 on the AMR crisis and the critical need for improved antimicrobial stewardship to tackle AMR evolution.

Lower-dose Intravenous Immunoglobulin Therapy for Geriatric Inflammatory Bowel Disease Accompanied by COVID-19 Multisystem Inflammatory Syndrome: a Case Report (preprint)

Background this article presents a noteworthy case of SARS-CoV-2-associated inflammatory bowel disease (IBD) in an elderly individual who endured three hospitalizations without favorable response to conventional treatment. Ultimately, the patient's symptoms subsided following the administration of intravenous immunoglobulin (IVIg).Case presentation : the patient, an elderly individual, experienced short-term fever and sore throat after encountering the COVID-19 pandemic. Despite receiving a three-dose inactivated COVID-19 vaccine, the patient tested positive for SARS-CoV-2 antigen and developed worsening symptoms, including diarrhea and recurrent fever. Initial antibiotic treatment for bacterial enteritis proved ineffective. Further evaluation, including endoscopy and pathology, confirmed the diagnosis of IBD with concurrent multisystem inflammatory syndrome (MIS) in adults. Following lower-dose IVIg administration, the patient's symptoms improved, with resolution of fever, diarrhea, and inflammation.Conclusions the case highlights the complexity of diagnosis and treatment in geriatric with IBD and MIS, emphasizing the importance of early intervention with IVIg. Further research is needed to explore the relationship between COVID-19 infection, MIS, and acute autoimmune diseases, as well as the efficacy of IVIg in these conditions.

Clinical Characteristics of 427 Unvaccinated Chinese Adult Patients with Maintenance Hemodialysis infected with SARS-CoV-2 Omicron subvariant BA.5.2 (preprint)

To analyze the clinical characteristics and outcomes of unvaccinated adult patients on maintenance hemodialysis infected with SARS-CoV-2 Omicron subvariant BA.5.2.The clinical data of 427 maintenance hemodialysis patients infected with SARS-CoV-2 Omicron subvariant BA.5.2 in our hospital were retrospectively collected. The patients were grouped according to the severity of the disease and compared. The clinical outcome and two-month follow-up were analyzed.These results suggest that CRP level, procalcitonin level, and bicarbonate concentration are related to the severity of disease caused by SARS-CoV-2 omicron BA.5.2 infection in unimmunized MHD patients. In addition, the co-bacterial infection may be an important cause of severe illness. Therefore, strengthen the treatment of critically ill patients, and actively and effectively control infection and secondary infection; Effective vaccination is the key to improving clinical outcomes to prevent the conversion of ordinary patients to severe and critical cases. Fever, age, ORF1ab gene value, and arterial oxygen partial pressure may be independent risk factors for disease severity in COVID-19 patients.

Metagenomics characterization of respiratory viral RNA pathogens in children under five years with severe acute respiratory infection in the Free State, South Africa.

Prompt detection of viral respiratory pathogens is crucial in managing respiratory infection including severe acute respiratory infection (SARI). Metagenomics next-generation sequencing (mNGS) and bioinformatics analyses remain reliable strategies for diagnostic and surveillance purposes. This study evaluated the diagnostic utility of mNGS using multiple analysis tools compared with multiplex real-time PCR for the detection of viral respiratory pathogens in children under 5 years with SARI. Nasopharyngeal swabs collected in viral transport media from 84 children admitted with SARI as per the World Health Organization definition between December 2020 and August 2021 in the Free State Province, South Africa, were used in this study. The obtained specimens were subjected to mNGS using the Illumina MiSeq system, and bioinformatics analysis was performed using three web-based analysis tools; Genome Detective, One Codex and Twist Respiratory Viral Research Panel. With average reads of 211323, mNGS detected viral pathogens in 82 (97.6%) of the 84 patients. Viral aetiologies were established in nine previously undetected/missed cases with an additional bacterial aetiology (Neisseria meningitidis) detected in one patient. Furthermore, mNGS enabled the much needed viral genotypic and subtype differentiation and provided significant information on bacterial co-infection despite enrichment for RNA viruses. Sequences of nonhuman viruses, bacteriophages, and endogenous retrovirus K113 (constituting the respiratory virome) were also uncovered. Notably, mNGS had lower detectability rate for severe acute respiratory syndrome coronavirus 2 (missing 18/32 cases). This study suggests that mNGS, combined with multiple/improved bioinformatics tools, is practically feasible for increased viral and bacterial pathogen detection in SARI, especially in cases where no aetiological agent could be identified by available traditional methods.

Changes in the incidence of community-acquired upper urinary tract infections caused by extended-spectrum beta-lactamase-producing Escherichia coli in Japanese children, 2016-2022 (preprint)

Background Urinary tract infections caused by extended-spectrum beta-lactamase (ESBL)-producing bacteria are increasing worldwide. At our hospital, the number of children hospitalized with upper urinary tract infections (UUTI) caused by ESBL-producing Escherichia coli had been a major problem since 2016. However, since the start of the COVID-19 pandemic in 2020, the proportion of ESBL-producing E. coli has changed. This study reviewed the trends in admissions of children to the hospital with UUTI caused by E. coli. Methods This retrospective study included patients who were hospitalized in the pediatric department of Matsue Red Cross Hospital with UUTI caused by E. coli. Medical and hospital records were reviewed to assess patient characteristics, antimicrobial use density, and days of antibiotic therapy at the hospital from January 1, 2016 to December 31, 2022. Results Over the study period, 80 children were admitted to the hospital with their first episode of bacterial UUTI. The total number of children hospitalized in the pediatric department decreased. However, the proportion of children with UUTI per total number of hospitalized children remained stable over the study period. Urine sample analyses showed that the proportion of ESBL-producing E. coli decreased significantly in 2020 to 2022. Antimicrobial use density and days of therapy of oral third-generation cephems was significantly correlated with the proportion of UUTI caused by ESBL-producing E. coli in pediatric patients. Conclusion Effective hygiene measures and appropriate use of antibiotics especially, oral third-generation cephems, are effective for reducing the incidence of ESBL-producing bacterial infections.

Co-infection of respiratory pathogens in SARS-CoV-2 positive patients at North West India, Rajasthan.

PURPOSE: Infection due to SARS-CoV-2 shows wide spectrum of disease from asymptomatic to severe disease and death. Coinfection of SARS-CoV-2 with other respiratory pathogens may affect the severity of disease and its outcome. Identification of other respiratory pathogens may help to initiate proper management and avoid unnecessary complications. MATERIALS AND METHODS: Total 250 SARS-COV-2 positive patients admitted in S.M.S hospitalwere included in study. Throat and nasopharyngeal swabs samples were collected in Viral Transport Medium (VTM) and nucleic acid extraction was done by automated EasyMag extractor and tested for 20 respiratory viruses and two bacteria by real time PCR. RESULTS: Out of 250 SARS CoV2 positive samples, 176 (70%) were positive for other respiratory pathogens also. The highest co-infection was due to HCoVOC43 (32.8%) virus followed by bacterial co-infection with S. pneumoniae (14.8%). Six (2.4%) patients with co-infection were on ventilator with age >65yr and three (1.2%) died during treatment. All three cases were found to have other co-morbid diseases like; asthma, Parkinson's and hypertension. CONCLUSION: High number of patients were found to have coinfection with other viruses and bacteria, timely identification and providing specific treatment to these patients can help improve outcome.

The Dark Side of Nosocomial Infections in Critically Ill COVID-19 Patients (preprint)

Coronavirus disease 2019 (COVID-19) is a potentially serious acute respiratory infection caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Since the World Health Organization (WHO) declared COVID-19 a global pandemic, the virus has spread to more than 200 countries with more than 500 million cases and more than 6 million deaths reported globally. It has long been known that viral respiratory tract infections predispose patients to bacterial infections and that these co-infections often have an unfavourable clinical outcome. Moreover, nosocomial infections, also known as health care-associated infections (HAIs), are those infections that are absent at the time of admission and acquired after hospitalization. However, the impact of coinfections or secondary infections on the progression of COVID-19 disease and its lethal outcome is still debated. The aim of this review was to assess the literature on the incidence of bacterial co-infections and superinfections in patients with COVID-19. The review also highlights the importance of the rational use of antibiotics in patients with COVID-19 and the need to implement antimicrobial stewardship principles to prevent the transmission of drug-resistant organisms in healthcare settings. Finally, alternative antimicrobial agents to counter the emergence of multidrug-resistant bacteria causing healthcare-associated infections in COVID-19 patients will also be discussed.