BIOMEDICA CRO’s Post

Amino acid catabolite markers for early prognostication of pneumonia in patients with COVID-19. ABSTRACT: Effective early-stage markers for predicting which patients are at risk of developing SARS-CoV-2 infection have not been fully investigated. Here, we performed comprehensive serum metabolome analysis of a total of 83 patients from two cohorts to determine that the acceleration of amino acid catabolism within 5 days from disease onset correlated with future disease severity. Increased levels of de-aminated amino acid catabolites involved in the de novo nucleotide synthesis pathway were identified as early prognostic markers that correlated with the initial viral load. We further employed mice models of SARS-CoV2-MA10 and influenza infection to demonstrate that such de-amination of amino acids and de novo synthesis of nucleotides were associated with the abnormal proliferation of airway and vascular tissue cells in the lungs during the early stages of infection. Consequently, it can be concluded that lung parenchymal tissue remodeling in the early stages of respiratory viral infections induces systemic metabolic remodeling and that the associated key amino acid catabolites are valid predictors for excessive inflammatory response in later disease stages. Source: Nat Commun https://lnkd.in/eucMCrMR

Epidemiological data attribute hospitalized COVID-19 patients an increased risk for COVID-19 associated VTE. Higher rates of VTE were observed in COVID-19 ICU cohorts. PE (Pulmonary Embolism) was comparable or even more prevalent to DVT (Deep Vein Thrombosis) suggesting a role of in-situ pulmonary thrombi formation, which may be a disease-specific feature in COVID-19. In-situ pulmonary thrombi formation may be driven by endothelial dysfunction, immunothrombotic processes and formation of NETs. COVID-19 has been initially defined as a contagious disease affecting primarily the upper and lower respiratory tract. However, at a later stage in the pandemic, non-respiratory symptoms and the involvement of other organ systems than respiratory system were also observed in COVID-19. COVID-19-associated vasculopathies, including venous (VTE) and arterial thromboembolism (ATE) and to a minor extent also vasculitic changes, have been described among patients with COVID-19, which complicate the clinical course and increase mortality. This review gives an overview of epidemiological, diagnostic, therapeutic and prognostic aspects of COVID-19 associated vasculopathies. https://lnkd.in/gY8itEeW For endothelial dysfunction implicated in post-COVID-19, clinical trials are listed on ClinicalTrials.gov testing the impact of interventions on post-COVID-19 endothelial function. ● (NCT05185934, NCT05252923, and NCT05371925) use glycocalyx-targeted interventions (sulodexide, a low-molecular-weight heparin, and Endocalyx, a dietary supplement). ● (NCT04631536) uses a combination of atorvastatin, ascorbic acid, folate, nicorandil, and nevibulol, ● (NCT05531019) uses an antioxidant derived from sea urchin eggs. ● (NCT04813718, NCT05227170, and NCT05556733) aim to target the gut microbiota to improve endothelial function post-COVID-19. The concept of targeting the gut microbiota to improve cardiovascular health is well-founded in prior animal and human studies. The intestinal immune system plays a critical role in systemic immunity, and its interaction with the systemic immune system plays a crucial role in determining the severity and outcomes of common pulmonary infections. The composition of the gut microbiota impacts the efficacy of COVID-19 vaccination, and SARS-CoV-2 infection alters the composition and metabolism of the gut microbiome, correlating with systemic host immune responses and inflammatory markers. Pathological alterations in the composition of the gut microbiota have been observed for at least 6 months postinfection and are associated with greater residual systemic inflammation and PASC symptoms, matching well with the pattern of impaired endothelial function in these patients. Read more : https://lnkd.in/gxxub_eC #covid #VTE #DVT #ATE #PE #PASC #therapeutic #gutmicrobiota #systemicinflammation Diagram Courtesy : Aljadah M, et al. Jacc adv. 2024;3(8):101070

Non-human primate model of long-COVID identifies immune associates of hyperglycemia Abstract Hyperglycemia, and exacerbation of pre-existing deficits in glucose metabolism, are manifestations of the post-acute sequelae of SARS-CoV-2. Our understanding of metabolic decline after acute COVID-19 remains unclear due to the lack of animal models. Here, we report a non-human primate model of metabolic post-acute sequelae of SARS-CoV-2 using SARS-CoV-2 infected African green monkeys. Using this model, we identify a dysregulated blood chemokine signature during acute COVID-19 that correlates with elevated and persistent hyperglycemia four months post-infection. Hyperglycemia also correlates with liver glycogen levels, but there is no evidence of substantial long-term SARS-CoV-2 replication in the liver and pancreas. Finally, we report a favorable glycemic effect of the SARS-CoV-2 mRNA vaccine, administered on day 4 post-infection. Together, these data suggest that the African green monkey model exhibits important similarities to humans and can be utilized to assess therapeutic candidates to combat COVID-related metabolic defects. Continued....click on the image in the banner below to access entire study results, its authors and their references. Posted by Larry Cole

Synbiotics in post-acute COVID-19 syndrome—a potential new treatment framework? As the world continues to recover from the impact of the COVID-19 pandemic, a new challenge has emerged in the form of post-acute COVID-19 syndrome (PACS), also known as long COVID. Characterised by multisystem involvement, PACS can lead to a substantial decline in quality of life, presenting a complex clinical picture that spans persistent debilitating cardiopulmonary, gastrointestinal, and neuropsychiatric symptoms, alongside profound fatigue. An estimated 65 million people worldwide are thought to have PACS, with a consequent effect on global workforces1. No effective treatment has yet been identified. Emerging evidence underscores the importance of the gut microbiome in the pathophysiology of long COVID, with a notable disruption in microbial balance, termed gut dysbiosis, identified in some individuals.2 The rationale for exploring the gut microbiome is grounded in its well-established role in immune modulation,3 a connection that is pertinent given the increasing evidence linking the prolonged symptoms of PACS to a persistent dysregulated immune response after infection.4, 5 In patients with COVID-19, especially those with persistent symptoms, alterations in gut flora have been verified through metagenomic sequencing of faecal samples.2 This gut dysbiosis has also been found to correlate with increased gut inflammation, compromised gut wall integrity, and systemic inflammatory dysfunction.6

In honor of attending #CIMM2024, I wanted to share a recent article showcasing the dynamic interplay between gut microbiota and metabolic interactions. To persuade my husband to get the annual flu shot, I usually treat him to Andy's Frozen Custard, which is certainly worth it considering how awful the flu can be! Check out this article on how we might improve flu treatment with a metabolite one day. Introduction: 📚Background: The gut-lung axis holds a key to understanding respiratory infections like the influenza A virus (IAV). Recent studies shed light on how gut microbiota influence immune defense, with germ-free and antibiotic-treated mice showing heightened susceptibility to severe IAV infection. By integrating systemic targeted metabolomics with other omics approaches like shotgun metagenomics, researchers can investigate relationship between gut microbial metabolites, host metabolism, and disease severity, contributing to a deeper understanding of the pathogenic mechanisms and potential therapeutic interventions. 💡So what?: This work points to the potential of indole-3-propionic acid (IPA) revolutionize our approach to influenza treatment and prevention. Methods: 👀 The effects of indole-3-propionic acid (IPA) supplementation on IAV infection in mice with treatment either before or after IAV infection, extending for several days. 🔬 Assessed cytokine levels, viral load, gut microbiota composition, gene expression, and metabolites expression. Results: 🦠 Gut microbiota undergoes significant shifts during flu infection, affecting diversity and bacterial species. 🧪 Metabolic pathways in the gut microbiota are altered, impacting ATP synthesis and carbohydrate metabolism. 🔀 Gene expression related to metabolic pathways changes, influencing fatty acid biosynthesis and lipid metabolism. 📊 Flu infection causes diverse alterations in gut microbiota metabolism, affecting lipopolysaccharide and amino acid synthesis. 🔄 Microbial metabolite concentrations change significantly, affecting host metabolism and immune response. 🔗 Certain gut bacteria correlate with metabolites, indicating complex relationships within the gut microbiota. 📉 Microbial metabolites and taxa strongly correlate with flu severity markers, affecting infection outcomes. 🍃 IPA supplementation reduces flu severity by restoring levels and mitigating viral load and inflammation. 📈 Depletion of IPA worsens flu severity, emphasizing its critical role in controlling the infection. Conclusion: 💪 Integrated multi-omics analysis unveils IPA as a pivotal modulator of influenza severity, with implications for disease management strategies. Paper: 'Shotgun metagenomics and systemic targeted metabolomics highlight indole-3-propionic acid as a protective gut microbial metabolite against influenza infection' in 'Gut Microbes' from Taylor & Francis Group using the biocrates life sciences ag #Quant500. #Microbiome #InfluenzaResearch #Immunity

Tackling Tick Troubles: Insights and Impacts of Lyme Disease in Ireland The rising prevalence of tick-borne infections (TBIs) is a growing concern in Ireland. A recent study investigated the types of TBIs, their symptoms, and the effectiveness of combination antibiotic treatments in a large patient cohort. Among 301 patients, 46.51% tested positive for TBIs, with the majority infected by Borrelia. The study found that combination antibiotics significantly reduced pain and neurological symptoms, demonstrating good patient tolerance and effectiveness in alleviating TBI symptoms. Further research focused on clinical biomarkers in 110 patients before and after antibiotic treatment. Initially, patients had low counts of several immune cells, including CD3%, CD3+ cells, and CD4+ helper cells. Post-treatment, most of these counts improved, highlighting the potential of standard clinical markers in assisting TBI diagnosis. However, CD8+ counts showed no notable progress, indicating the need for more research on immune responses to TBIs. Pain is a common and debilitating symptom of TBIs, particularly in patients with post-treatment Lyme disease syndrome (PTLDS). An Irish hospital study explored the relationship between pain and biomarkers in TBI patients before and after antibiotic treatment. Pain ratings significantly decreased post-treatment, suggesting persistent infections responsive to antibiotics. Although some biomarkers were correlated with pain ratings, they did not directly predict pain changes. This finding underscores the importance of appropriate antibiotic treatment and the human rights implications of withholding pain relief. Beyond the health impacts, TBIs also impose a significant economic burden. A study estimated the prevalence and cost of Chronic Lyme Disease (CLD) in Ireland, revealing an annual cost of 40,699 EUR per patient and a national total of 305.24 million EUR. Timely detection and treatment of Lyme disease can reduce these costs and prevent long-term complications. The study called for enhanced training for general practitioners and increased awareness among policymakers about the impact of Lyme disease, comparing its prevalence to that of the COVID-19 pandemic. By synthesizing these studies, it is evident that Lyme disease and other TBIs pose significant health and economic challenges in Ireland. Improved diagnostic markers, effective treatments, and comprehensive healthcare policies are crucial in managing and mitigating the impact of these infections. #tickplex www.tezted.com @tez_ted See also the video at https://lnkd.in/dzUyZEcX https://lnkd.in/dXQgHgBH https://lnkd.in/dug9Q7ah https://lnkd.in/dt9e63pp

Tackling Tick Troubles: Insights and Impacts of Lyme Disease in Ireland The rising prevalence of tick-borne infections (TBIs) is a growing concern in Ireland. A recent study investigated the types of TBIs, their symptoms, and the effectiveness of combination antibiotic treatments in a large patient cohort. Among 301 patients, 46.51% tested positive for TBIs, with the majority infected by Borrelia. The study found that combination antibiotics significantly reduced pain and neurological symptoms, demonstrating good patient tolerance and effectiveness in alleviating TBI symptoms. Further research focused on clinical biomarkers in 110 patients before and after antibiotic treatment. Initially, patients had low counts of several immune cells, including CD3%, CD3+ cells, and CD4+ helper cells. Post-treatment, most of these counts improved, highlighting the potential of standard clinical markers in assisting TBI diagnosis. However, CD8+ counts showed no notable progress, indicating the need for more research on immune responses to TBIs. Pain is a common and debilitating symptom of TBIs, particularly in patients with post-treatment Lyme disease syndrome (PTLDS). An Irish hospital study explored the relationship between pain and biomarkers in TBI patients before and after antibiotic treatment. Pain ratings significantly decreased post-treatment, suggesting persistent infections responsive to antibiotics. Although some biomarkers were correlated with pain ratings, they did not directly predict pain changes. This finding underscores the importance of appropriate antibiotic treatment and the human rights implications of withholding pain relief. Beyond the health impacts, TBIs also impose a significant economic burden. A study estimated the prevalence and cost of Chronic Lyme Disease (CLD) in Ireland, revealing an annual cost of 40,699 EUR per patient and a national total of 305.24 million EUR. Timely detection and treatment of Lyme disease can reduce these costs and prevent long-term complications. The study called for enhanced training for general practitioners and increased awareness among policymakers about the impact of Lyme disease, comparing its prevalence to that of the COVID-19 pandemic. By synthesizing these studies, it is evident that Lyme disease and other TBIs pose significant health and economic challenges in Ireland. Improved diagnostic markers, effective treatments, and comprehensive healthcare policies are crucial in managing and mitigating the impact of these infections. #tickplex www.tezted.com @tez_ted See also the video at https://lnkd.in/dFvQ7DdV https://lnkd.in/daC3VHb6 https://lnkd.in/dhWfSQtv https://lnkd.in/dsxu_3fX

Using a targeted metabolomics approach to explore differences in ARDS associated with COVID-19 compared to ARDS caused by H1N1 influenza and bacterial pneumonia. Acute respiratory distress syndrome (ARDS) is a life-threatening critical care syndrome commonly associated with infections such as COVID-19, influenza, and bacterial pneumonia. Ongoing research aims to improve our understanding of ARDS, including its molecular mechanisms, individualized treatment options, and potential interventions to reduce inflammation and promote lung repair. OBJECTIVE: To map and compare metabolic phenotypes of different infectious causes of ARDS to better understand the metabolic pathways involved in the underlying pathogenesis. METHODS: We analyzed metabolic phenotypes of 3 ARDS cohorts caused by COVID-19, H1N1 influenza, and bacterial pneumonia compared to non-ARDS COVID-19-infected patients and ICU-ventilated controls. Targeted metabolomics was performed on plasma samples from a total of 150 patients using quantitative LC-MS/MS and DI-MS/MS analytical platforms. RESULTS: Distinct metabolic phenotypes were detected between different infectious causes of ARDS. There were metabolomics differences between ARDSs associated with COVID-19 and H1N1, which include metabolic pathways involving taurine and hypotaurine, pyruvate, TCA cycle metabolites, lysine, and glycerophospholipids. ARDSs associated with bacterial pneumonia and COVID-19 differed in the metabolism of D-glutamine and D-glutamate, arginine, proline, histidine, and pyruvate. The metabolic profile of COVID-19 ARDS (C19/A) patients admitted to the ICU differed from COVID-19 pneumonia (C19/P) patients who were not admitted to the ICU in metabolisms of phenylalanine, tryptophan, lysine, and tyrosine. Metabolomics analysis revealed significant differences between C19/A, H1N1/A, and PNA/A vs ICU-ventilated controls, reflecting potentially different disease mechanisms. CONCLUSION: Different metabolic phenotypes characterize ARDS associated with different viral and bacterial infections. Source: Crit Care https://lnkd.in/eYd-2zns

📃Scientific paper: The Role of Procalcitonin as an Antimicrobial Stewardship Tool in Patients Hospitalized with Seasonal Influenza Abstract: Background: Up to 60% of the antibiotics prescribed to patients hospitalized with seasonal influenza are unnecessary. Procalcitonin (PCT) has the potential as an antimicrobial stewardship program (ASP) tool because it can differentiate between viral and bacterial etiology. We aimed to explore the role of PCT as an ASP tool in hospitalized seasonal influenza patients. Methods: We prospectively included 116 adults with seasonal influenza from two influenza seasons, 2018–2020. All data was obtained from a single clinical setting and analyzed by descriptive statistics and regression models. Results: In regression analyses, we found a positive association of PCT with 30 days mortality and the amount of antibiotics used. Influenza diagnosis was associated with less antibiotic use if the PCT value was low. Patients with a low initial PCT (<0.25 µg/L) had fewer hospital and intensive care unit (ICU) days and fewer positive chest X-rays. PCT had a negative predictive value of 94% for ICU care stay, 98% for 30 days mortality, and 88% for bacterial coinfection. Conclusion: PCT can be a safe rule-out test for bacterial coinfection. Routine PCT use in seasonal influenza patients with an uncertain clinical picture, and rapid influenza PCR testing, may be efficient as ASP tools. Continued on ES/IODE ➡️ https://etcse.fr/HaE ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

Perhaps it's useful for someone to know that eating more carbohydrates than your body can handle and creating states of high blood sugar, is impairing your immune system. Take this article for example ⬇️ Chronic hyperglycemia impairs anti-microbial function of macrophages in response to Mycobacterium tuberculosis infection. https://lnkd.in/geM-DXuS  It discusses the relationship between Diabetes Mellitus (DM) and increased susceptibility to tuberculosis (TB), with a specific focus on how high blood sugar levels (hyperglycemia) impact the innate immune response, particularly the function of macrophages. Macrophages are the body's first line of defense against infections. They act by engulfing pathogens and secreting various molecules that play roles in both pro-inflammatory and anti-inflammatory responses. This study discusses how these cells' ability to produce reactive oxygen species (ROS), reactive nitrogen species (RNS), and pro-inflammatory cytokines (like IL-1β and IL-6) is impaired under conditions of high blood sugar. And as if that isn't bad enough, under conditions of high blood sugar we see the production of anti-inflammatory cytokines (such as IL-10) increases.  This imbalance can lead to a reduced capacity to fight off infections, like Mycobacterium tuberculosis, the bacterium that causes TB. The article goes on to teach that in a state of hyperglycemia, macrophages show decreased levels of activation and differentiation markers (specifically, TLR-4, CD11b, and CD11c). Why is that a problem? Keep reading. I will tell you ⬇️ This decreased activation status means a compromised ability of these cells to respond adequately to infections. This diminished response is posited as a reason for the higher susceptibility to TB observed in individuals with diabetes. High blood sugar levels, which can result from consuming more carbohydrates than the body can efficiently manage, not only increase the risk of developing diabetes but also impair the body's innate defense mechanisms against infections. So don't let anyone tell you that what you eat doesn't have an influence on your immune system function. Because it really does and it can. And when it comes to having a functioning immune system, and as a result good brain health, your metabolic health matters. The next time I get sick, I assure you, I will not be reaching for that sugary ginger ale. Even though that would be the nostalgic thing to do and be the advice of my mama. :) #immunesystem #immunehealth #metabolism #hyperglycemia