Examining B-cell dynamics and responsiveness in different inflammatory milieus using an agent-based model

PLoS Computational Biology, Год журнала: 2024, Номер 20(1), С. e1011776 - e1011776

Опубликована: Янв. 23, 2024

Introduction B-cells are essential components of the immune system that neutralize infectious agents through generation antigen-specific antibodies and phagocytic functions naïve memory B-cells. However, B-cell response can become compromised by a variety conditions alter overall inflammatory milieu, be due to substantial, acute insults as seen in sepsis, or those produce low-level, smoldering background inflammation such diabetes, obesity, advanced age. This dysfunction, mediated cytokines Interleukin-6 (IL-6) Tumor Necrosis Factor-alpha (TNF-α), increases susceptibility late-stage sepsis patients nosocomial infections incidence severity recurrent infections, SARS-CoV-2, with chronic conditions. We propose modeling dynamics aid investigation their responses different levels patterns systemic inflammation. Methods The Immunity Agent-based Model (BCIABM) was developed integrating knowledge regarding B-cells, short-lived plasma cells, long-lived regulatory along various differentiation pathways cytokines/mediators. BCIABM calibrated reflect physiologic behaviors to: 1) mild antigen stimuli expected result sensitization effective memory, 2) severe challenges representing substantial during previously documented studies on behavior septic patients. Once calibrated, used simulate repeat states low, inflammation, implemented low IL-6 TNF-α often responsiveness were evaluated validated comparing Veteran’s Administration (VA) patient cohort COVID-19 infection known have higher comorbidities. Results successfully able reproduce appropriate development exposure, well immunoparalysis Simulation experiments then revealed significantly decreased increased, reproducing data VA population. Conclusion proved useful dynamically mechanisms function reproduced across range exposures statuses. These results elucidate previous demonstrating similar negative correlation between positing an established conserved mechanism explains dysfunction wide phenotypic presentations.

Язык: Английский

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Does Pre-existing Diabetes Correlate with Long COVID-19 in Europe? Evidence from the Analysis of the Survey of Health, Ageing and Retirement in Europe’s Corona Surveys

Journal of Diabetes Research, Год журнала: 2024, Номер 2024, С. 1 - 7

Опубликована: Фев. 2, 2024

Background. A substantial proportion of those infected with COVID-19 are presenting persistent symptoms, referred to as long COVID-19. Emerging evidence suggests that the presence pre-existing chronic conditions, such diabetes, may increase risk Objectives. To investigate whether having diabetes increases developing in population middle-aged and older adults (≥50 years old) Europe, while assessing if this relationship can be accounted for or is modified by known factors (age, sex, hospitalization, hypertension, weight status). Methods. population-based longitudinal prospective study involving a sample respondents aged 50 ( n=4,004 ) probable confirmed infection from 27 countries participated both waves 7 8 Survey Health, Ageing Retirement Europe its 2020 2021 Corona Surveys. Logistic regression modeling was performed. Results. Overall, 66.8% affected reported at least one symptom; 55.2% were female, average age 64.6 years; 13.2% had diabetes. Respondents significantly higher odds COVID-19, compared without OR=1.37 ; 95% CI=1.12,1.68 ). This remained significant OR=2.00 98% CI=0.25,1.14 after adjusting sex OR=1.64 females; CI=1.43,1.88 ), hospitalization illness OR=3.19 CI=2.41,4.23 hypertension OR=1.17 CI=1.01,1.36 overweight OR=1.31 CI=1.11,1.56 obese OR=1.77 CI=1.44,2.19 status. The effect on moderated age; it highest OR=2.00 CI=1.28,3.14 then, declined age. Conclusions. There between even controlling literature-based confounding factors, moderating relationship.

Язык: Английский

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Molecular Mechanisms Responsible for Diabetogenic Effects of COVID-19 Infection—Induction of Autoimmune Dysregulation and Metabolic Disturbances

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(14), С. 11576 - 11576

Опубликована: Июль 18, 2023

The COVID-19 pandemic has revealed a significant association between SARS-CoV-2 infection and diabetes, whereby individuals with diabetes are more susceptible to severe disease higher mortality rates. Interestingly, recent findings suggest reciprocal relationship wherein may contribute developing new-onset worsen existing metabolic abnormalities. This narrative review aims shed light on the intricate molecular mechanisms underlying diabetogenic effects of COVID-19. Specifically, explores potential role various factors, including direct damage β-cells, insulin resistance triggered by systemic inflammation, disturbances in hormonal regulation, aiming enhance our understanding impact development progression diabetes. By analysing these mechanisms, aim is binding angiotensin-converting enzyme 2 (ACE2) receptors, which present key organs tissues, interfere glucometabolic pathways, leading hyperglycaemia, potentially new mechanisms. virus’s β-cells through invasion or inflammation induce disrupt glucose homeostasis. Furthermore, glucocorticoids, commonly used treat COVID-19, exacerbate hyperglycaemia resistance, contributing long-term metabolism still unknown, necessitating further research into possibility novel type article provides comprehensive overview current interaction highlighting areas for future therapeutic interventions.

Язык: Английский

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Inflammatory Modulation of Interleukin-17 and -23 in Long COVID Diabetic Patients

Journal of Angiotherapy, Год журнала: 2024, Номер 8(3)

Опубликована: Март 20, 2024

Background: The global COVID-19 pandemic has brought forth a persistent challenge in the form of Post-COVID-19 Syndrome (PCS) or Long COVID, affecting approximately 1 10 cases. Among various risk factors, diabetes emerged as significant predictor severe outcomes, with hyperglycemia and hyperinflammation playing pivotal roles. Despite known association, exact mechanisms linking to COVID remain elusive, prompting need for further investigation. This study aimed explore relationship between immune responses, particularly interleukin-17 -23 levels, severity diabetic individuals. Method: Fifty patients were compared fifty controls. Blood cytokine levels measured, was assessed using Severity Scale (PCS-SS). Results: Results revealed elevated those without condition. Additionally, participants reported significantly higher symptom across physical, psychological, cognitive domains, indicated by Scale. Conclusion: These findings underscore strong association heightened inflammatory responses increased Understanding these could inform targeted interventions improve outcomes this vulnerable population, highlighting importance tailored management strategies diabetics.

Язык: Английский

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Digital interventions for self-management of prediabetes: A scoping review

PLoS ONE, Год журнала: 2024, Номер 19(5), С. e0303074 - e0303074

Опубликована: Май 10, 2024

Background Rates of prediabetes, which can lead to type 2 diabetes, are increasing worldwide. Interventions for prediabetes mainly focus on lifestyle changes diet and exercise. While these interventions effective, they often delivered face-to-face, may pose a barrier those with limited access healthcare. Given the evidence digital addressing other noncommunicable diseases, also be effective self-management. The aim this scoping review was assess breadth around Methods We developed targeted search strategy relevant studies were identified through searches conducted in four bibliographic databases (Medline, Embase, PsycInfo, Scopus). Published eligible if included intervention support adults aged 18+ Titles abstracts first screened relevance by one researcher. Full texts selected records assessed against criteria independently two researchers inclusion final analysis. Results Twenty-nine included, nine randomised controlled trials. Most efficacy reported significant at least primary and/or secondary outcome, including participants’ glycaemic control, weight loss physical activity levels. About one-third mixed outcomes or early that not sustained long-term follow-up. varied length, modalities, complexity. Delivery formats text messages, mobile apps, virtually accessible dietitians/health coaches, online peer groups, web-based platforms. Approximately half participant engagement/acceptability outcomes. Conclusion Whilst here suggests self-management acceptable have potential reduce one’s risk progression more research is needed understand interventions, components specifically, greatest reach diverse populations, most promoting user engagement, longer term.

Язык: Английский

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