Pub Date : 2024-09-12DOI: 10.1101/2024.09.11.24313502
Roshan Ratnakar Naik, Nehal Kalita, Rajesh Kumar Maurya, Annie Rajan
Antimicrobial resistance (AMR) continues to be a major public threat due to dwindling supplies of effective antibiotics due to its excessive usage in humans and food producing animals. The objective of our study was to identify and predict future trends in multi-drug resistance amongst enterobacteriaceae and non-enterobacteriaceae family in India for four common broad-spectrum antibiotics. We focussed on four broad spectrum antibiotics levofloxacin, gentamicin, cefepime, and ceftazidime and classified the GEARS program study dataset into sensitive (S), intermediate(I) and resistant (R) isolates based on CLSI breakpoints . Levofloxacin (98.3%) was found to be the most susceptible broad spectrum antibiotic for treatment of non-enterobacteriaceae while it was relatively resistant (56.5%) for enterobacteriaceae treatment. As levofloxacin are among ICMR list of alert antimicrobial agents,hospitals and clinicans can exercise greater care before prescribing them.
{"title":"Antibiotic susceptibility trend estimation for India based on 2018 to 2021 data from GEARS program","authors":"Roshan Ratnakar Naik, Nehal Kalita, Rajesh Kumar Maurya, Annie Rajan","doi":"10.1101/2024.09.11.24313502","DOIUrl":"https://doi.org/10.1101/2024.09.11.24313502","url":null,"abstract":"Antimicrobial resistance (AMR) continues to be a major public threat due to dwindling supplies of effective antibiotics due to its excessive usage in humans and food producing animals. The objective of our study was to identify and predict future trends in multi-drug resistance amongst enterobacteriaceae and non-enterobacteriaceae family in India for four common broad-spectrum antibiotics. We focussed on four broad spectrum antibiotics levofloxacin, gentamicin, cefepime, and ceftazidime and classified the GEARS program study dataset into sensitive (S), intermediate(I) and resistant (R) isolates based on CLSI breakpoints . Levofloxacin (98.3%) was found to be the most susceptible broad spectrum antibiotic for treatment of non-enterobacteriaceae while it was relatively resistant (56.5%) for enterobacteriaceae treatment. As levofloxacin are among ICMR list of alert antimicrobial agents,hospitals and clinicans can exercise greater care before prescribing them.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142189545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1101/2024.09.12.24313545
Hanmeng Xu, Camilla Aparicio, Aanchal Wats, Barbara L. Araujo, Virginia E. Pitzer, Joshua L. Warren, Eugene D. Shapiro, Linda M. Niccolai, Daniel M. Weinberger, Carlos R. Oliveira
IMPORTANCE: Nirsevimab, a long-acting monoclonal antibody, has demonstrated efficacy against RSV-related lower respiratory tract infections (LRTIs) in clinical trials. Post-licensure monitoring is essential to confirm these benefits in real-world settings.OBJECTIVE: To evaluate the real-world effectiveness of nirsevimab against medically attended RSV infections in infants and to assess how effectiveness varies by disease severity, dosage, and time since immunization.DESIGN, SETTING, AND PARTICIPANTS: This test-negative case-control study used inpatient, outpatient, and emergency room data from the Yale New Haven Health System. Nirsevimab- eligible infants who were tested for RSV using polymerase chain reaction between October 1, 2023 and May 9, 2024 were included. Cases were infants with confirmed RSV infections; controls were those who tested negative.EXPOSURE: Nirsevimab immunization, verified through state immunization registries.MAIN OUTCOMES AND MEASURES: Effectiveness was estimated using multivariable logistic regression, adjusting for age, calendar month, and individual risk factors. Separate models examined effectiveness by clinical setting, disease severity, dose, and time since immunization. Broader outcomes, including all-cause LRTI and LRTI-related hospitalization, were also analyzed, with stratification by early and late respiratory seasons.RESULTS: The analytic sample included 3,090 infants (median age 6.7 months, IQR 3.6-9.7), with 680 (22.0%) RSV-positive and 2,410 (78.0%) RSV-negative. 21 (3.1%) RSV-positive and 309 (12.8%) RSV-negative infants received nirsevimab. Effectiveness against RSV infection was 68.4% (95% CI, 50.3%-80.8%). Effectiveness was 61.6% (95% CI, 35.6%-78.6%) for outpatient visits and 80.5% (95% CI, 52.0%-93.5%) for hospitalizations. The highest effectiveness, 84.6% (95% CI, 58.7%-95.6%), was observed against severe RSV outcomes requiring ICU admission or high-flow oxygen. Although effectiveness against RSV infections declined over time, it remained significant at 55% (95% credible interval, 16%-75%) at 14 weeks post-immunization. Protective effectiveness was also observed against all-cause LRTI and LRTI-related hospitalizations during peak RSV season (49.4% [95% CI, 10.7%-72.9%] and 79.1% [95% CI, 27.6%-94.9%], respectively). However, from February to May, when RSV positivity was low, effectiveness against these broader outcomes was negligible.CONCLUSIONS AND RELEVANCE: Nirsevimab provided substantial protection against RSV- related outcomes for at least three months. These findings support the continued use of nirsevimab and provide evidence that may help build public confidence in the immunization program.
{"title":"Real-World Effectiveness of Nirsevimab Against Respiratory Syncytial Virus: A Test-Negative Case-Control Study","authors":"Hanmeng Xu, Camilla Aparicio, Aanchal Wats, Barbara L. Araujo, Virginia E. Pitzer, Joshua L. Warren, Eugene D. Shapiro, Linda M. Niccolai, Daniel M. Weinberger, Carlos R. Oliveira","doi":"10.1101/2024.09.12.24313545","DOIUrl":"https://doi.org/10.1101/2024.09.12.24313545","url":null,"abstract":"IMPORTANCE: Nirsevimab, a long-acting monoclonal antibody, has demonstrated efficacy against RSV-related lower respiratory tract infections (LRTIs) in clinical trials. Post-licensure monitoring is essential to confirm these benefits in real-world settings.\u0000OBJECTIVE: To evaluate the real-world effectiveness of nirsevimab against medically attended RSV infections in infants and to assess how effectiveness varies by disease severity, dosage, and time since immunization.\u0000DESIGN, SETTING, AND PARTICIPANTS: This test-negative case-control study used inpatient, outpatient, and emergency room data from the Yale New Haven Health System. Nirsevimab- eligible infants who were tested for RSV using polymerase chain reaction between October 1, 2023 and May 9, 2024 were included. Cases were infants with confirmed RSV infections; controls were those who tested negative.\u0000EXPOSURE: Nirsevimab immunization, verified through state immunization registries.\u0000MAIN OUTCOMES AND MEASURES: Effectiveness was estimated using multivariable logistic regression, adjusting for age, calendar month, and individual risk factors. Separate models examined effectiveness by clinical setting, disease severity, dose, and time since immunization. Broader outcomes, including all-cause LRTI and LRTI-related hospitalization, were also analyzed, with stratification by early and late respiratory seasons.\u0000RESULTS: The analytic sample included 3,090 infants (median age 6.7 months, IQR 3.6-9.7), with 680 (22.0%) RSV-positive and 2,410 (78.0%) RSV-negative. 21 (3.1%) RSV-positive and 309 (12.8%) RSV-negative infants received nirsevimab. Effectiveness against RSV infection was 68.4% (95% CI, 50.3%-80.8%). Effectiveness was 61.6% (95% CI, 35.6%-78.6%) for outpatient visits and 80.5% (95% CI, 52.0%-93.5%) for hospitalizations. The highest effectiveness, 84.6% (95% CI, 58.7%-95.6%), was observed against severe RSV outcomes requiring ICU admission or high-flow oxygen. Although effectiveness against RSV infections declined over time, it remained significant at 55% (95% credible interval, 16%-75%) at 14 weeks post-immunization. Protective effectiveness was also observed against all-cause LRTI and LRTI-related hospitalizations during peak RSV season (49.4% [95% CI, 10.7%-72.9%] and 79.1% [95% CI, 27.6%-94.9%], respectively). However, from February to May, when RSV positivity was low, effectiveness against these broader outcomes was negligible.\u0000CONCLUSIONS AND RELEVANCE: Nirsevimab provided substantial protection against RSV- related outcomes for at least three months. These findings support the continued use of nirsevimab and provide evidence that may help build public confidence in the immunization program.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142189583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1101/2024.09.10.24313452
Abdul Waaje, Md Sumon Sarkar, Md Zahidul Islam
The severe acute respiratory syndrome coronavirus 2 (SARSCoV 2) is a coronavirus variation responsible for COVID19, the respiratory disease that triggered the COVID19 pandemic. The primary aim of our study is to elucidate the complex network of interactions between SARS CoV 2, tuberculosis, and lung cancer employing a bioinformatics and network biology approach. Lung cancer is the leading cause of significant illness and death connected to cancer worldwide. Tuberculosis (TB) is a prevalent medical condition induced by the Mycobacterium bacteria. It mostly affects the lungs but may also have an influence on other areas of the body. Coronavirus disease (COVID19) causes a risk of respiratory complications between lung cancer and tuberculosis. SARSCoV 2 impacts the lower respiratory system and causes severe pneumonia, which can significantly increase the mortality risk in individuals with lung cancer. We conducted transcriptome analysis to determine molecular biomarkers and common pathways in lung cancer, TB, and COVID19, which provide understanding into the association of SARSCoV 2 to lung cancer and tuberculosis. Based on the compatible RNA-seq data, our research employed GREIN and NCBI's Gene Expression Omnibus (GEO) to perform differential gene expression analysis. Our study exploited three RNAseq datasets from the Gene Expression Omnibus (GEO) GSE171110, GSE89403, and GSE81089 to identify distinct relationships between differentially expressed genes (DEGs) in SARSCoV 2, tuberculosis, and lung cancer. We identified 30 common genes among SARSCoV 2, tuberculosis, and lung cancer (25 upregulated genes and 5 downregulated genes). We analyzed the following five databases: WikiPathway, KEGG, Bio Carta, Elsevier Pathway and Reactome. Using Cytohubba's MCC and Degree methods, We determined the top 15 hub genes resulting from the PPI interaction. These hub genes can serve as potential biomarkers, leading to novel treatment strategies for disorders under investigation. Transcription factors (TFs) and microRNAs (miRNAs) were identified as the molecules that control the differentially expressed genes (DEGs) of interest, either during transcription or after transcription. We identified 35 prospective therapeutic compounds that form significant differentially expressed genes (DEGs) in SARSCoV 2, lung cancer, and tuberculosis, which could potentially serve as medications. We hypothesized that the potential medications that emerged from this investigation may have therapeutic benefits.
{"title":"Network biology and bioinformatics-based framework to identify the impacts of SARS-CoV-2 infections on lung cancer and tuberculosis","authors":"Abdul Waaje, Md Sumon Sarkar, Md Zahidul Islam","doi":"10.1101/2024.09.10.24313452","DOIUrl":"https://doi.org/10.1101/2024.09.10.24313452","url":null,"abstract":"The severe acute respiratory syndrome coronavirus 2 (SARSCoV 2) is a coronavirus variation responsible for COVID19, the respiratory disease that triggered the COVID19 pandemic. The primary aim of our study is to elucidate the complex network of interactions between SARS CoV 2, tuberculosis, and lung cancer employing a bioinformatics and network biology approach. Lung cancer is the leading cause of significant illness and death connected to cancer worldwide. Tuberculosis (TB) is a prevalent medical condition induced by the Mycobacterium bacteria. It mostly affects the lungs but may also have an influence on other areas of the body. Coronavirus disease (COVID19) causes a risk of respiratory complications between lung cancer and tuberculosis. SARSCoV 2 impacts the lower respiratory system and causes severe pneumonia, which can significantly increase the mortality risk in individuals with lung cancer. We conducted transcriptome analysis to determine molecular biomarkers and common pathways in lung cancer, TB, and COVID19, which provide understanding into the association of SARSCoV 2 to lung cancer and tuberculosis. Based on the compatible RNA-seq data, our research employed GREIN and NCBI's Gene Expression Omnibus (GEO) to perform differential gene expression analysis. Our study exploited three RNAseq datasets from the Gene Expression Omnibus (GEO) GSE171110, GSE89403, and GSE81089 to identify distinct relationships between differentially expressed genes (DEGs) in SARSCoV 2, tuberculosis, and lung cancer. We identified 30 common genes among SARSCoV 2, tuberculosis, and lung cancer (25 upregulated genes and 5 downregulated genes). We analyzed the following five databases: WikiPathway, KEGG, Bio Carta, Elsevier Pathway and Reactome. Using Cytohubba's MCC and Degree methods, We determined the top 15 hub genes resulting from the PPI interaction. These hub genes can serve as potential biomarkers, leading to novel treatment strategies for disorders under investigation. Transcription factors (TFs) and microRNAs (miRNAs) were identified as the molecules that control the differentially expressed genes (DEGs) of interest, either during transcription or after transcription. We identified 35 prospective therapeutic compounds that form significant differentially expressed genes (DEGs) in SARSCoV 2, lung cancer, and tuberculosis, which could potentially serve as medications. We hypothesized that the potential medications that emerged from this investigation may have therapeutic benefits.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142189584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1101/2024.09.11.24313457
Eva Kozanli, Angelique Winkel, Alvin X. Han, Sharon van den Brink, Annemarie van den Brandt, Milly E. Haverkort, Sjoerd M Euser, Colin A Russell, Menno de Jong, Marlies A van Houten, Steven F.L. van Lelyveld, Dirk Eggink
This study compared the dynamics of SARS-CoV-2 viral shedding in saliva between wild-type virus-infected and Omicron-infected household cohorts. Pre-existing immunity in participants likely shortens duration of viral shedding and lowers viral load peaks. Dense saliva sampling can be a convenient tool to study viral load dynamics.
{"title":"Shortened SARS-CoV-2 shedding in saliva during early Omicron compared to wild-type pandemic phase","authors":"Eva Kozanli, Angelique Winkel, Alvin X. Han, Sharon van den Brink, Annemarie van den Brandt, Milly E. Haverkort, Sjoerd M Euser, Colin A Russell, Menno de Jong, Marlies A van Houten, Steven F.L. van Lelyveld, Dirk Eggink","doi":"10.1101/2024.09.11.24313457","DOIUrl":"https://doi.org/10.1101/2024.09.11.24313457","url":null,"abstract":"This study compared the dynamics of SARS-CoV-2 viral shedding in saliva between wild-type virus-infected and Omicron-infected household cohorts. Pre-existing immunity in participants likely shortens duration of viral shedding and lowers viral load peaks. Dense saliva sampling can be a convenient tool to study viral load dynamics.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142189548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1101/2024.09.12.24313525
EBRAHIM Abbasi, Mohammad Djaefar Moemenbellah-Fard
Introduction: Arboviruses, including Chikungunya (CHIKV), Dengue (DENV), and West Nile (WNV) viruses, are significant viral threats that affect numerous people globally each year. This report explores the prevalence of these viruses in Iran through a systematic review and meta-analysis.Methods: The present survey was performed with a systematic review and meta-analysis method on the seroprevalence of WNV, CHIKV, and DENV using the ELISA test. Based on this, by search in Web of Science, PubMed, Scopus, Cochrane Library, Science Direct, and Google Scholar scientific databases, all relevant published papers were sorted out and reviewed. Power ratification of data was carried out with a random effects model in meta-analysis, meta-regression, I2 index, and Egger test.Results: Twelve published papers between 2000 and 2024 were embodied in this meta-analysis report. The seroprevalence of positive ELISA test for WNV in Iran was estimated at 12.9% (CI=95%: 7.4-18.4), and for CHIKV at 6.2% (CI=95%: 0.6-11.8). Regarding DENV, only two studies were conducted with a zero prevalence in one study, and a seroprevalence of 5.6% in another study.Conclusion: According to these data, WNV, CHIKV, and DENV fevers have been detected in Iran using ELISA test. Considering the seropositivity of WNV and CHIKV, and the finding of these viruses from several provinces, it could be for granted that these two viruses are ubiquitous and DENV fever is sporadic in Iran.Keywords: Arbovirus, Chikungunya, Dengue, ELISA, Meta-analysis, Virus, WNV.
{"title":"Prevalence of Chikungunya, Dengue, and West Nile arboviruses in Iran based on enzyme-linked immunosorbent assay (ELISA): A systematic review and meta-analysis","authors":"EBRAHIM Abbasi, Mohammad Djaefar Moemenbellah-Fard","doi":"10.1101/2024.09.12.24313525","DOIUrl":"https://doi.org/10.1101/2024.09.12.24313525","url":null,"abstract":"Introduction: Arboviruses, including Chikungunya (CHIKV), Dengue (DENV), and West Nile (WNV) viruses, are significant viral threats that affect numerous people globally each year. This report explores the prevalence of these viruses in Iran through a systematic review and meta-analysis.\u0000Methods: The present survey was performed with a systematic review and meta-analysis method on the seroprevalence of WNV, CHIKV, and DENV using the ELISA test. Based on this, by search in Web of Science, PubMed, Scopus, Cochrane Library, Science Direct, and Google Scholar scientific databases, all relevant published papers were sorted out and reviewed. Power ratification of data was carried out with a random effects model in meta-analysis, meta-regression, I2 index, and Egger test.\u0000Results: Twelve published papers between 2000 and 2024 were embodied in this meta-analysis report. The seroprevalence of positive ELISA test for WNV in Iran was estimated at 12.9% (CI=95%: 7.4-18.4), and for CHIKV at 6.2% (CI=95%: 0.6-11.8). Regarding DENV, only two studies were conducted with a zero prevalence in one study, and a seroprevalence of 5.6% in another study.\u0000Conclusion: According to these data, WNV, CHIKV, and DENV fevers have been detected in Iran using ELISA test. Considering the seropositivity of WNV and CHIKV, and the finding of these viruses from several provinces, it could be for granted that these two viruses are ubiquitous and DENV fever is sporadic in Iran.\u0000Keywords: Arbovirus, Chikungunya, Dengue, ELISA, Meta-analysis, Virus, WNV.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142189549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.1101/2024.09.10.24313403
Timon Kuchler, Andrea Ribeiro, Maciej Lech, Javier Carbajo-Lozoya, Kristina Adorjan, Hans Christian Stubbe, Martina Seifert, Anna Wöhnle, Veronika Kessler, Johanna Negele, Uwe Heemann, Christoph Schmaderer
Background: SARS-CoV-2 infection may lead to Post-COVID Syndrome (PCS), characterized by debilitating symptoms like persistent fatigue, cardiovascular symptoms, and cognitive dysfunction. Persistent endothelial dysfunction (ED) is a potential driver of ongoing symptoms. Yet, the underlying biological mechanisms remain unclear. Methods: In this prospective observational study, we characterized 41 PCS patients and 24 healthy controls (HC, matched out of n=204, recruited before the pandemic) and investigated the effect of SARS-CoV-2 Spike protein 1 (S1) and plasma from PCS patients on human retinal endothelial cells (HREC). Results: Plasma samples from PCS patients exhibited significantly elevated erythropoietin, VEGF and MCP-1 alongside decreased IL-6 levels compared to HC. Low Haemoglobin and Haematocrit were negatively associated with PCS severity. VEGF levels were positively correlated with Anti-S1 IgG levels in patients and upregulated on mRNA level in HREC exposed to S1. Additionally, S1 exposure promoted ROS production and transiently activated HIF-1α in HREC. Persistent activation of HIF-2α by S1 led to disrupted endothelial integrity. HREC exposed to plasma from severely affected PCS patients showed increased ROS and compromised barrier function. Treatment with Belzutifan, a HIF-2α inhibitor, restored barrier integrity in HREC exposed to S1 or PCS-plasma. Conclusion: These findings suggest that HIF-2α-mediated ED in PCS might be a potential therapeutical target for Belzutifan.
{"title":"Inhibition of HIF-2α Pathway as a Potential Therapeutic Strategy for Endothelial Dysfunction in Post-COVID Syndrome","authors":"Timon Kuchler, Andrea Ribeiro, Maciej Lech, Javier Carbajo-Lozoya, Kristina Adorjan, Hans Christian Stubbe, Martina Seifert, Anna Wöhnle, Veronika Kessler, Johanna Negele, Uwe Heemann, Christoph Schmaderer","doi":"10.1101/2024.09.10.24313403","DOIUrl":"https://doi.org/10.1101/2024.09.10.24313403","url":null,"abstract":"Background: SARS-CoV-2 infection may lead to Post-COVID Syndrome (PCS), characterized by debilitating symptoms like persistent fatigue, cardiovascular symptoms, and cognitive dysfunction. Persistent endothelial dysfunction (ED) is a potential driver of ongoing symptoms. Yet, the underlying biological mechanisms remain unclear. Methods: In this prospective observational study, we characterized 41 PCS patients and 24 healthy controls (HC, matched out of n=204, recruited before the pandemic) and investigated the effect of SARS-CoV-2 Spike protein 1 (S1) and plasma from PCS patients on human retinal endothelial cells (HREC). Results: Plasma samples from PCS patients exhibited significantly elevated erythropoietin, VEGF and MCP-1 alongside decreased IL-6 levels compared to HC. Low Haemoglobin and Haematocrit were negatively associated with PCS severity. VEGF levels were positively correlated with Anti-S1 IgG levels in patients and upregulated on mRNA level in HREC exposed to S1. Additionally, S1 exposure promoted ROS production and transiently activated HIF-1α in HREC. Persistent activation of HIF-2α by S1 led to disrupted endothelial integrity. HREC exposed to plasma from severely affected PCS patients showed increased ROS and compromised barrier function. Treatment with Belzutifan, a HIF-2α inhibitor, restored barrier integrity in HREC exposed to S1 or PCS-plasma. Conclusion: These findings suggest that HIF-2α-mediated ED in PCS might be a potential therapeutical target for Belzutifan.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142189550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Neonatal sepsis, a systemic inflammatory response to infection, is a major cause of morbidity and mortality in newborns. Neutrophil extracellular trap formation (NETosis), while crucial for pathogen clearance, can contribute to organ dysfunction in sepsis. This study aimed to identify key NETosis-related genes for prognostication in neonatal sepsis.Methods: We analysed whole blood transcriptome datasets (GSE26440, GSE26378, GSE25504) from neonates with sepsis and controls. Differentially expressed NETosis genes (DE-NET genes) were identified, and a machine learning approach was used to select the most influential genes. A NET score model was constructed and validated using single-sample gene set enrichment analysis (ssGSEA). The model's performance was evaluated using ROC analysis. The interplay between key-NET genes and the complement-coagulation (CC) system was investigated. Clinical samples were also collected for validation .Results: Sixteen DE-NET genes were identified, and LASSO further refined these to 8 key-NET genes. The key-NET gene signature and NET score model showed excellent predictive performance (AUCs > 89%) in distinguishing survivors from non-survivors. Mediation analysis revealed that key-NET gene expression precedes and potentially drives complement-coagulation activation.Conclusions: We present an 8-gene prognostic model for risk stratification in neonatal sepsis, based on early blood transcript signatures in neonates. Our findings underscore the central role of NETosis in sepsis-induced coagulopathy, revealing potential therapeutic targets for intervention.
{"title":"Decoding the Deadly Dance: NETosis Genes Predict Neonatal Sepsis Fate","authors":"Deepshikha Shaw, Sridhar Santhanam, Tapas Kumar Som, Samsiddhi Bhattacharjee, Saroj Kant Mohapatra","doi":"10.1101/2024.09.10.24313397","DOIUrl":"https://doi.org/10.1101/2024.09.10.24313397","url":null,"abstract":"Background: Neonatal sepsis, a systemic inflammatory response to infection, is a major cause of morbidity and mortality in newborns. Neutrophil extracellular trap formation (NETosis), while crucial for pathogen clearance, can contribute to organ dysfunction in sepsis. This study aimed to identify key NETosis-related genes for prognostication in neonatal sepsis.\u0000Methods: We analysed whole blood transcriptome datasets (GSE26440, GSE26378, GSE25504) from neonates with sepsis and controls. Differentially expressed NETosis genes (DE-NET genes) were identified, and a machine learning approach was used to select the most influential genes. A NET score model was constructed and validated using single-sample gene set enrichment analysis (ssGSEA). The model's performance was evaluated using ROC analysis. The interplay between key-NET genes and the complement-coagulation (CC) system was investigated. Clinical samples were also collected for validation .\u0000Results: Sixteen DE-NET genes were identified, and LASSO further refined these to 8 key-NET genes. The key-NET gene signature and NET score model showed excellent predictive performance (AUCs > 89%) in distinguishing survivors from non-survivors. Mediation analysis revealed that key-NET gene expression precedes and potentially drives complement-coagulation activation.\u0000Conclusions: We present an 8-gene prognostic model for risk stratification in neonatal sepsis, based on early blood transcript signatures in neonates. Our findings underscore the central role of NETosis in sepsis-induced coagulopathy, revealing potential therapeutic targets for intervention.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142189546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.1101/2024.09.10.24313399
Ai-ris Collier, Katherine McMahan, Catherine Jacob-Dolan, Jinyan Liu, Erica Borducchi, Bernard Moss, Dan H. Barouch
The replication-incompetent modified vaccinia Ankara-Bavarian Nordic vaccine (MVA-BN; Jynneos) was deployed during the 2022 clade IIb mpox outbreak. On August 14, 2024, the World Health Organization declared the mpox clade Ib outbreak in the Democratic Republic of the Congo a public health emergency of international concern, which has raised the question about the durability of vaccine immunity after MVA-BN vaccination. In this study, we show that the MVA-BN vaccine generated mpox serum antibody responses that largely waned after 6-12 months.
{"title":"Rapid Decline of Mpox Antibody Responses Following MVA-BN Vaccination","authors":"Ai-ris Collier, Katherine McMahan, Catherine Jacob-Dolan, Jinyan Liu, Erica Borducchi, Bernard Moss, Dan H. Barouch","doi":"10.1101/2024.09.10.24313399","DOIUrl":"https://doi.org/10.1101/2024.09.10.24313399","url":null,"abstract":"The replication-incompetent modified vaccinia Ankara-Bavarian Nordic vaccine (MVA-BN; Jynneos) was deployed during the 2022 clade IIb mpox outbreak. On August 14, 2024, the World Health Organization declared the mpox clade Ib outbreak in the Democratic Republic of the Congo a public health emergency of international concern, which has raised the question about the durability of vaccine immunity after MVA-BN vaccination. In this study, we show that the MVA-BN vaccine generated mpox serum antibody responses that largely waned after 6-12 months.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142189547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-10DOI: 10.1101/2024.09.09.24313234
Alessandra Isabella Romero Ramirez, Anushri Somasundaran, Konstantina Kontogianni, Jacob Parkes, Yusra Hussain, Susan Gould, Christopher T Williams, Dominic Wooding, Richard Body, Hayley E Hardwick, J Kenneth Baillie, Jake Dunning, Malcolm Gracie Semple, CONDOR steering group, ISARIC CCP UK investigators, Tom Fletcher, Thomas Edwards, Devy Emperador, Ana I Cubas Atienzar
ObjectivesEvaluation of diagnostic accuracy of two point-of-care (POC) molecular diagnostic tests for the detection of monkeypox virus (MPXV): Xpert Mpox (Cepheid, Inc., USA) and STANDARD M10 MPX/OPX (SD Biosensor, Inc., Korea).MethodsDiagnostic accuracy of both platforms was evaluated using 53 upper-respiratory swabs (URS) and 32 skin lesions swabs (SS) collected from mpox and COVID-19 patients in the UK against the Sansure (Sansure Biotech Inc.) and the CDC reference qPCR tests. The analytical sensitivity of both platforms was assessed using a viral isolate from the lineage II, B.1.ResultsThe limit of detection was 1x101 pfu/ml for both tests. The overall sensitivity and specificity of the Xpert Mpox was 97.67% [95% CI 87.71-99.94%] and 88.57% [95% CI 73.26-96.80%] and 97.44% [95% CI 86.52-99.94%] and 74.42% [95% CI 58.83-86.48%] comparing the Sansure and CDC qPCR, respectively and for the M10 MPX/OPX was 87.80% [95% CI 73.80-95.92%] and 76.60% [95% CI 61.97-87.70%] and 94.29% [95% CI 80.84-99.30%] and 86.67% [95% CI 73.21-94.95%] with the Sansure and CDC qPCR. ConclusionThe Xpert Mpox had good diagnostic accuracy for both sample types while the M10 MPX/OPX clinical accuracy was deficient with URS. Our data supports the use of URS during the first 3 days of symptoms onset for mpox diagnosis.
目的评估两种用于检测猴痘病毒（MPXV）的床旁（POC）分子诊断测试的诊断准确性：Xpert Mpox（美国 Cepheid 公司）和 STANDARD M10 MPX/OPX （韩国 SD 生物传感器公司）：方法使用从英国的猴痘和COVID-19患者身上采集的53份上呼吸道拭子（URS）和32份皮损拭子（SS），对照Sansure（Sansure Biotech Inc.）和CDC参考qPCR检验，评估了这两种平台的诊断准确性。结果两种检测方法的检测限均为 1x101 pfu/ml。Xpert Mpox 的总体灵敏度和特异性分别为 97.67%[95% CI 87.71-99.94%]和 88.57%[95% CI 73.26-96.80%]和 97.44%[95% CI 86.52-99.94%]和 74.42%[95% CI 58.83-86.48%]。与 Sansure 和 CDC qPCR 相比，M10 MPX/OPX 分别为 87.80% [95% CI 73.80-95.92%] 和 76.60% [95% CI 61.97-87.70%] 以及 94.29% [95% CI 80.84-99.30%] 和 86.67% [95% CI 73.21-94.95%]。结论 Xpert Mpox 对两种样本类型都有很好的诊断准确性，而 M10 MPX/OPX 对 URS 的临床准确性不足。我们的数据支持在出现症状的头 3 天内使用 URS 诊断麻痘。
{"title":"Evaluation of the diagnostic accuracy and analytical sensitivity of the novel Xpert Mpox (Cepheid) and STANDARD M10 MPX/OPX (SD Biosensor) molecular point-of-care assays for the detection of Mpox virus in skin lesion swabs and upper-respiratory swab samples","authors":"Alessandra Isabella Romero Ramirez, Anushri Somasundaran, Konstantina Kontogianni, Jacob Parkes, Yusra Hussain, Susan Gould, Christopher T Williams, Dominic Wooding, Richard Body, Hayley E Hardwick, J Kenneth Baillie, Jake Dunning, Malcolm Gracie Semple, CONDOR steering group, ISARIC CCP UK investigators, Tom Fletcher, Thomas Edwards, Devy Emperador, Ana I Cubas Atienzar","doi":"10.1101/2024.09.09.24313234","DOIUrl":"https://doi.org/10.1101/2024.09.09.24313234","url":null,"abstract":"Objectives\u0000Evaluation of diagnostic accuracy of two point-of-care (POC) molecular diagnostic tests for the detection of monkeypox virus (MPXV): Xpert Mpox (Cepheid, Inc., USA) and STANDARD M10 MPX/OPX (SD Biosensor, Inc., Korea).\u0000Methods\u0000Diagnostic accuracy of both platforms was evaluated using 53 upper-respiratory swabs (URS) and 32 skin lesions swabs (SS) collected from mpox and COVID-19 patients in the UK against the Sansure (Sansure Biotech Inc.) and the CDC reference qPCR tests. The analytical sensitivity of both platforms was assessed using a viral isolate from the lineage II, B.1.\u0000Results\u0000The limit of detection was 1x101 pfu/ml for both tests. The overall sensitivity and specificity of the Xpert Mpox was 97.67% [95% CI 87.71-99.94%] and 88.57% [95% CI 73.26-96.80%] and 97.44% [95% CI 86.52-99.94%] and 74.42% [95% CI 58.83-86.48%] comparing the Sansure and CDC qPCR, respectively and for the M10 MPX/OPX was 87.80% [95% CI 73.80-95.92%] and 76.60% [95% CI 61.97-87.70%] and 94.29% [95% CI 80.84-99.30%] and 86.67% [95% CI 73.21-94.95%] with the Sansure and CDC qPCR. Conclusion\u0000The Xpert Mpox had good diagnostic accuracy for both sample types while the M10 MPX/OPX clinical accuracy was deficient with URS. Our data supports the use of URS during the first 3 days of symptoms onset for mpox diagnosis.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142189577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-10DOI: 10.1101/2024.09.09.24313322
Dolores Mullen, Jessica Edney, Dawn Phillips, Ruth Wilkie, David Reid, Catherine M Lowndes, Erna Buitendam, Katy Sinka, Catherine H Mercer, John Saunders, Hamish Mohammed, Dana Ogaz
Mpox is an infectious disease transmitted through close contact. It is caused by the monkeypox virus, which is endemic to some countries of West and Central Africa. A multi-country outbreak of mpox occurred in 2022, and the UK experienced rapid community transmission associated with sexual contact, mainly, but not exclusively among networks of GBMSM. In response to the outbreak in the UK, a reactive mpox vaccination programme was targeted to those most at risk. We explore the uptake and course completion of mpox vaccination in GBMSM taking part in an online survey in 2023. Findings from this community sample indicate vaccination uptake in around two-thirds of participants meeting mpox proxy eligibility criteria with high levels of course completion among all and eligible participants that were ever vaccinated. Vaccine non-offer was a barrier to uptake, as nearly a third of those eligible but unvaccinated reported never having received an mpox vaccine offer. Continued targeting of vaccination to GBMSM at highest risk of mpox at SHS, with community-support, will help facilitate equitable uptake of vaccination.
{"title":"Mpox vaccination uptake in a UK community sample of gay, bisexual, and other men who have sex with men (GBMSM) the year following the 2022 Clade IIb mpox outbreak","authors":"Dolores Mullen, Jessica Edney, Dawn Phillips, Ruth Wilkie, David Reid, Catherine M Lowndes, Erna Buitendam, Katy Sinka, Catherine H Mercer, John Saunders, Hamish Mohammed, Dana Ogaz","doi":"10.1101/2024.09.09.24313322","DOIUrl":"https://doi.org/10.1101/2024.09.09.24313322","url":null,"abstract":"Mpox is an infectious disease transmitted through close contact. It is caused by the monkeypox virus, which is endemic to some countries of West and Central Africa. A multi-country outbreak of mpox occurred in 2022, and the UK experienced rapid community transmission associated with sexual contact, mainly, but not exclusively among networks of GBMSM. In response to the outbreak in the UK, a reactive mpox vaccination programme was targeted to those most at risk. We explore the uptake and course completion of mpox vaccination in GBMSM taking part in an online survey in 2023. Findings from this community sample indicate vaccination uptake in around two-thirds of participants meeting mpox proxy eligibility criteria with high levels of course completion among all and eligible participants that were ever vaccinated. Vaccine non-offer was a barrier to uptake, as nearly a third of those eligible but unvaccinated reported never having received an mpox vaccine offer. Continued targeting of vaccination to GBMSM at highest risk of mpox at SHS, with community-support, will help facilitate equitable uptake of vaccination.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":"73 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142189551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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