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Coronavirus disease 2019 (COVID-19) is a respiratory infectious disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is characterized by having a heterogeneous disease course, ranging from asymptomatic and mild symptoms to more severe and critical cases. In most cases the severity of COVID-19 is related to host factors, especially deregulation of the immune response in patients. Even if COVID-19 indiscriminately affects individuals of different age group, ethnicity and economic status; most severe cases and disproportional mortality occur in elderly individuals. This point out that aging is one risk factor for unfavourable clinical outcomes among COVID-19 patients. The biology of aging is a complex process; Aging can alter the structure and function of cells, tissues, and organs resulting in impaired response to stress. Alongside with other systems, the immune system is also affected with the aging process. Immunosenescence is an age associated change in the immune system that affects the overall response to immunological challenges in the elderly. Similarly, apart from the normal inflammatory process, aging is associated with a low grade, sterile, chronic inflammation which is termed as inflammaging. We hypothesized that inflammaging and immunosenescence could play an important role in SARS-CoV-2 pathogenesis and poor recovery from COVID-19 in elderly individuals. This review summarizes the changes in the immune system with age and how these changes play part in the pathogenesis of SARS-CoV-2 and clinical outcome of COVID-19 which could add to the understanding of age associated targeted immunotherapy in the elderly.

Aging is a multifaceted process impacting cells, tissues, organs, and organ systems of the body. Like other systems, aging affects both the adaptive and the innate components of the immune system, a phenomenon known as immunosenescence. The deregulation of the immune system puts elderly individuals at higher risk of infection, lower response to vaccines, and increased incidence of cancer. In the Western world, overnutrition has increased the incidence of obesity (linked with chronic inflammation) which increases the risk of metabolic syndrome, cardiovascular disease, and cancer. Aging is also associated with inflammaging a sterile chronic inflammation that predisposes individuals to age‐associated disease. Genetic manipulation of the nutrient‐sensing pathway, fasting, and calorie restriction (CR) has been shown to increase the lifespan of model organisms. As well in humans, fasting and CR have also been shown to improve different health parameters. Yet the direct effect of fasting and CR on the aging immune system needs to be further explored. Identifying the effect of fasting and CR on the immune system and how it modulates different parameters of immunosenescence could be important in designing pharmacological or nutritional interventions that slow or revert immunosenescence and strengthen the immune system of elderly individuals. Furthermore, clinical intervention can also be planned, by incorporating fasting or CR with medication, chemotherapy, and vaccination regimes. This review discusses age‐associated changes in the immune system and how these changes are modified by fasting and CR which add information on interventions that promote healthy aging and longevity in the growing aging population. Aging is associated with the decline of immune function, increased incidence of infection, and cancer leading to an unhealthy and shorter lifespan. On the other hand, interventions like fasting and calorie restriction have been shown to promote healthier and longer lifespans by slowing/alerting the aging process.

COVID-19 is caused by SARS-CoV-2 and has a diverse spectrum of clinical presentations ranging from asymptomatic cases to severe and critical cases that result in the death of the patient. Alongside the viral factors host factors like Age, deregulation of the immune response and presence of comorbidity determine the patient’s outcome. Here we sought to assess the impact of age on natural antibody response, CBC-based inflammatory markers, and outcome of COVID-19 patients. We divided the participants into three groups, young (≤ 35 years), middle-aged (40–60 years), and old (≥ 65 years) patients and collected and analyzed sociodemographic, clinical, and laboratory parameters. We found that elderly patients showed higher ( P  < 0.05) levels of inflammation like increased neutrophil percentages, NLR, lymphopenia, and low Hgb levels, compared to middle-aged and young patients. Interestingly these markers were also associated with mortality of COVID-19 patients. On the other hand, no significant difference was observed in ion concentration, lipid profile, and coagulation test between the three age groups. We also found that elderly patients showed significantly ( P  < 0.05) decreased levels of natural antibody response to SARS-CoV-2 infection compared with the two groups. Lastly, we assessed the effect of dexamethasone treatment, even if statistically not significant ( P  > 0.05) we observed a positive trend among patients under dexamethasone in the aspect of decreasing inflammatory markers. To conclude we showed that SARS-CoV-2 is characterized by an age-dependent deregulation of inflammatory markers that are associated with mortality among COVID-19 patients.

Patients with type 2 diabetes (T2D) have a lower risk of Mycobacterium tuberculosis infection, progression from infection to tuberculosis (TB) disease, TB morality and TB recurrence, when being treated with metformin. However, a detailed mechanistic understanding of these protective effects is lacking. Here, we use mass cytometry to show that metformin treatment expands a population of memory-like antigen-inexperienced CD8 + CXCR3 + T cells in naive mice, and in healthy individuals and patients with T2D. Metformin-educated CD8 + T cells have increased (i) mitochondrial mass, oxidative phosphorylation, and fatty acid oxidation; (ii) survival capacity; and (iii) anti-mycobacterial properties. CD8 + T cells from Cxcr3 −/− mice do not exhibit this metformin-mediated metabolic programming. In BCG-vaccinated mice and guinea pigs, metformin enhances immunogenicity and protective efficacy against M. tuberculosis challenge. Collectively, these results demonstrate an important function of CD8 + T cells in metformin-derived host metabolic-fitness towards M. tuberculosis infection. Metformin is an anti-diabetic drug that has shown promise to reduce M. tuberculosis susceptibility. Here the authors show that this effect is a result of metformin-mediated activation of anti-mycobacterial memory-like antigen-inexperienced CD8 + CXCR3 + T cells, an effect that also boosts response to BCG vaccination.

Background Hepatitis B virus (HBV) is a major global public health issue and the most common etiology of chronic liver disease (CLD). The connection between Helicobacter pylori and patients who are HBsAg positive has not been thoroughly explored and has generated considerable scientific and clinical curiosity, although the debate persists. Objective This study aimed to assess serological and virological characteristics of HBsAg + liver disease patients with and without H. pylori infection. Methods From April 1, 2021, to March 30, 2022, a hospital-based cross-sectional study was conducted at the University of Gondar Comprehensive Specialized Hospital on 384 known HBsAg + liver disease patients recruited using a convenience sampling technique. All the 384 HBsAg + patients were tested for fecal H. pylori antigen. For HBeAg, HBeAb, and HBV-DNA analysis, we recruited only 50 subsamples randomly. Serological tests were performed using commercially available enzyme immunoassay Architect System kits. For virological investigations, HBV-DNA was extracted using the Abbott mSample Preparation System DNA, and then HBV viral load was determined by real-time PCR. GraphPad Prism 8.02 and SPSS 25 were used for data analysis, considering a statistically significant P-value of 0.05. Results H. pylori co-infection was found in 153 (39.8%) of HBsAg + study participants. The prevalence of HBeAg (5/25) and HBV-DNA (15/25) was higher among the H. pylori co-infected patient group, whereas HBeAb prevalence (11/25) was lower in the co-infected group. The levels of HBeAg ( p  < 0.04), HBeAb ( p  < 0.01), and HBV viral load ( p  < 0.006) were increased in H. pylori co-infected patients than in HBV mono-infected patients. Conclusions HBeAg and HBV-viral load were higher in H. pylori co-infected HBsAg + patients. These findings suggested that H. pylori has a role in the increment of clinical, serological, and virological parameters in HBsAg + liver diseases.

Background Nasal colonisation by bacteria occurs more frequently in immunocompromised patients than in healthy individuals. These colonizing bacteria can potentially lead to infections in cancer patients, especially as these patients tend to be immunocompromised. Objective To determine the prevalence of nasal bacterial colonization, antimicrobial susceptibility patterns, and risk factors for colonization among cancer patients at the Dessie Comprehensive Specialized Hospital in Ethiopia. Method A hospital-based cross-sectional study was conducted, from March 01 to June 30 2024. Socio-demographic and other data were collected using structured questionnaires and reviewing patient cards. Each nasal swab sample was cultivated on blood agar, chocolate agar, MacConkey agar, and mannitol salt agar, at 37 °C. Bacterial species were identified using gram stain, colony morphology, and standard biochemical tests. Kirby Bauer’s disc diffusion method was performed using Mueller Hinton agar to test for antimicrobial sensitivity. Data were collected, cleaned, entered into Epi-data 3.1, and analyzed using SPSS version 26. Descriptive statistics were presented with tables and figures, while logistic regression identified significant associations using odds ratios and 95% confidence intervals ( p  < 0.05). Results Nasal carriage rate of bacterial isolates were, 112/260, 43.1% (95% confidence interval 37.7%-49.2%). Out of the total nasal isolates, Staphylococcus aureus was the most common bacterial species (24.1%), followed by coagulase-negative staphylococci (21.4%), Streptococcus pneumoniae (14.3%), and Pseudomonas aeruginosa (10.7%). Multidrug resistance (MDR) was observed in 45.5% of isolates, with Klebsiella ozaenae and Acinetobacter species showing particularly high resistance rates. Notably, K. ozaenae exhibited complete resistance to all tested drugs, while Acinetobacter species demonstrated an 80% MDR rate. A history of hospital admission, smoking, nose and hand washing habits were significantly associated risk factors for the carriage rate. Conclusions and recommendations Nasal bacterial colonization in cancer patients may result in significant health issues. The antimicrobial resistance patterns were relatively high, which may reflect the participant’s hospitalization. Regular health education among those patients are recommended to potentially tackle nasal bacterial carriage.

Known as immunosenescence, the major dysregulation of the immune system with age is associated with poor vaccination efficacy, and increased susceptibility to infections, age-related pathologies, and neoplasms, with incidences exacerbated with age. Cellular senescence is a crucial process that puts cells in an irreversible cell-cycle arrest which prevents damaged or stressed cells from uncontrolled propagation and eventually potential malignancy. Paradoxically, senescence also contributes to the occurrence of cancer and increases the risk of metastasis through different secretory mediators. Altogether, the recent use of senotherapy to eliminate senescent cells has been shown to delay tumorigenesis, attenuate age-related deterioration of organs, and promote healthy aging. Interestingly, immune cells have been shown to specifically interact with, and kill senescent cells, thus opening new opportunities for the development of specific therapeutic strategies similar to immunotherapy in cancer. Through its detrimental impact on the immune system, immunosenescence is also leading to the accumulation of senescent cells with age thus further contributing to the occurrence and worsening of multiple age-related pathologies such as cancer. Understanding the molecular and cellular events occurring during the aging process, and triggering immunosenescence as well as the mechanisms by which senescent cells escape immune surveillance would help to improve immune responses to senescent cells and their clearance. In this review, we highlight how senescent cells interact with immune cells, and how immunosenescence-associated phenotypical and functional deregulation hinder the ability of immune cells to clear senescent cells. We further characterize strategies aimed at promoting the clearance of senescent cells by the immune system.

Ascites is a pathological collection of free fluid in the peritoneal cavity, which is a common complication in patients with cirrhosis, an advanced liver disease. Bacterial infection increases the mortality rate of hospitalized patients with cirrhosis, irrespective of the severity of the liver disease. Around 60% of patients with compensated cirrhosis developed ascites within 10 years during the course of their disease. The in-hospital mortality rate due to spontaneous bacterial peritonitis (SBP) could exceed 90%, but with early diagnosis and prompt antibiotic therapy, this rate has been shown to decrease to 20%. Here, we enrolled adult (age  ≥  18) patients with liver disease with evidence of cirrhosis who developed ascites and assessed the presence of spontaneous ascites fluid infection (SAFI) in these patients. Of the total 218 patients, 22.9% (50/218) develop ascites infection. The liver organ function tests like alanine aminotransferase, aspartate aminotransferase, total bilirubin, and direct bilirubin were found to be significantly ( P  < 0.05) higher in patients with ascites fluid infection compared to patients with non-ascites fluid infection. Of the gram-negative bacteria, K. pneumonia and E. coli were isolated and found to be 100% resistant to amoxicillin and clavulanate. From the gram-positive bacterial isolates,  S. aureus was only resistant to penicillin, whereas Str. viridans was resistant to ceftriaxone, cefotaxime, cefepime, and penicillin. On the other hand, clinical features such as a history of jaundice, low arterial blood pressure, and ultrasound results such as a shrunken liver and enlarged spleen were also independent predictors of spontaneous bacterial peritonitis. In conclusion, given the high probability of death following SAFI, early detection, and treatment, as well as knowledge of the microbial agent, resistance profile, and predictive markers in various contexts, are essential for the timely diagnosis and management of SAFI in these patients.

Aging is unlikely programmed but the result of a series of damages. Reducing the damages and/or improving the resilience to stressors may extend lifespan and healthspan. Advances in drug and vaccine development played an important role in extending lifespan in the world population by preventing and curing many infectious diseases which were fatal to humans in early days. The number of individuals over the age of 60 was 900 million in 2015 and this number is expected to rise to 2 billion by the year 2050. This demographic change is a current and future challenge of nations across the globe.Diabetes is one of the common diseases associated with aging and its risk increases with age. The number of individuals having diabetes has increased from 180 million in 1980 to 422 million in 2014 and its prevalence has almost doubled from 4.7% in 1980 to 8.5% in 2014 among the adult population. Low-grade chronic inflammation termed as “Inflammaging” is one feature of elderly individuals and it has been associated with different age-related disease. Pro-inflammatory cytokines like IL-6, TNF, and CRP have been associated with pathological conditions like diabetes, Alzheimer’s disease, and cardiovascular disease.Many aging studies directly compare young and old individuals to identify different changes associated with age including changes in the immune system. But few studies have shown that both young and old individuals are diverse and have a different aging trajectory. Here in this project, we tried to approach the aging process in two perspectives one is by chronological age and the other is by pathological age and looked for changes associated with chronic inflammation, immunosenescence, and functionality of the immune cell.With clinical data and structured questionnaires we stratified our groups in the elderly category: diabetic, pre-diabetic, non-diabetic but with other comorbidities, and healthy while we used young individuals as a control. We showed that even healthy aging is accompanied by low-grade inflammation. The situation worsens in individuals with diabetes and prediabetes. One important finding is the impact of treatments as individuals under metformin monotherapy have a lower level of inflammatory molecules like TNF, sTNFRI, and sTNRII. Five-year mortality data showed that diabetic individuals under metformin monotherapy had a lower mortality rate compared to diabetic patients under other nonmetformin therapy.The classical signs of aging and immunosenescence were present in the cohort we have studied (i) decrease of naïve CD4 and CD8 T cells (ii) increase in CD16-expressing monocytes (iii) increase in frequency of mature NK cells. On the other hand, diabetic and pre-diabetic individuals displayed further reduced naïve/memory ratio (define with CD27 and CD45RO). Similarly to the observation on inflammation diabetic individuals taking metformin have closer immune cell signature of healthy old individuals. To have insight into the pro/anti-inflammatory capacity of immune cells, their activation revealed that healthy old individuals had a higher level of both pro-inflammatory molecules like TNF, IL-6 and antiinflammatory molecule like IL-10 compared to young individuals. Lastly we asses the effect of metformin on chronic inflammation and its potential immunomodulatory role in vitro using PBMCs and in vivo in mice.

Lack of diversity and proportionate representation in genomics datasets and databases contributes to inequity in healthcare outcomes globally1,2. The relationships of human diversity with biological and biomedical phenotypes are pervasive3, yet remain understudied, particularly in a single-cell genomics context. Here we present the Asian Immune Diversity Atlas (AIDA), a multi-national single-cell RNA-sequencing (scRNA-seq) healthy reference atlas of human immune cells. AIDA comprises 1,265,624 circulating immune cells from 619 healthy donors and 6 controls, spanning 7 population groups across 5 countries. AIDA is one of the largest healthy blood datasets in terms of number of cells, and also the most diverse in terms of number of population groups. Though population groups are frequently compared at the continental level, we identified a pervasive impact of sub-continental diversity on cellular and molecular properties of immune cells. These included cell populations and genes implicated in disease risk and pathogenesis as well as those relevant for diagnostics. We detected single-cell signatures of human diversity not apparent at the level of cell types, as well as modulation of the effects of age and sex by self-reported ethnicity. We discovered functional genetic variants influencing cell type-specific gene expression, including context-dependent effects, which were under-represented in analyses of non-Asian population groups, and which helped contextualise disease-associated variants. We validated our findings using multiple independent datasets and cohorts. AIDA provides fundamental insights into the relationships of human diversity with immune cell phenotypes, enables analyses of multi-ancestry disease datasets, and facilitates the development of precision medicine efforts in Asia and beyond.