Infection In Elderly Individuals Research Articles

Differences in virus and immune dynamics for SARS-CoV-2 Delta and Omicron infections by age and vaccination histories

Vaccination against COVID-19 was integral to controlling the pandemic that persisted with the continuous emergence of SARS-CoV-2 variants. Using a mathematical model describing SARS-CoV-2 within-host infection dynamics, we estimate differences in virus and immunity due to factors of infecting variant, age, and vaccination history (vaccination brand, number of doses and time since vaccination). We fit our model in a Bayesian framework to upper respiratory tract viral load measurements obtained from cases of Delta and Omicron infections in Singapore, of whom the majority only had one nasopharyngeal swab measurement. With this dataset, we are able to recreate similar trends in URT virus dynamics observed in past within-host modelling studies fitted to longitudinal patient data.We found that Omicron had higher R0,within values than Delta, indicating greater initial cell-to-cell spread of infection within the host. Moreover, heterogeneities in infection dynamics across patient subgroups could be recreated by fitting immunity-related parameters as vaccination history-specific, with or without age modification. Our model results are consistent with the notion of immunosenescence in SARS-CoV-2 infection in elderly individuals, and the issue of waning immunity with increased time since last vaccination. Lastly, vaccination was not found to subdue virus dynamics in Omicron infections as well as it had for Delta infections.This study provides insight into the influence of vaccine-elicited immunity on SARS-CoV-2 within-host dynamics, and the interplay between age and vaccination history. Furthermore, it demonstrates the need to disentangle host factors and changes in pathogen to discern factors influencing virus dynamics. Finally, this work demonstrates a way forward in the study of within-host virus dynamics, by use of viral load datasets including a large number of patients without repeated measurements.

Factors Related to Caregivers' Intention to Vaccinate Their Elderly Family Members with Major Neurocognitive Disorders against COVID-19.

Vaccination helps reduce the risk of coronavirus disease 2019 (COVID-19) infection in elderly individuals with major neurocognitive disorders (MNDs). However, some caregivers are hesitant to have their elderly family members with MNDs vaccinated against COVID-19. This study explored the factors influencing caregivers' intentions to vaccinate elderly family members with MNDs against COVID-19. A total of 232 caregivers of elderly family members with MNDs participated in this study. In this survey, data regarding COVID-19 vaccination acceptance, fear, side effects, family members' attitudes toward vaccination, mental health status, neuropsychiatric symptoms, and cognitive impairments were collected from the elderly participants with MNDs. The associations between these variables and the caregivers' intention to vaccinate their elderly family members with MNDs against COVID-19 were examined using a multivariable linear regression analysis model. The results revealed that caregivers' perceived familial support for vaccination, the perceived value of vaccination, and autonomy to vaccinate elder family members were positively correlated with caregivers' intention to vaccinate elderly family members with MNDs, whereas elderly family members' age was negatively correlated with caregiver intentions. This study demonstrated that caregiver factors (perceived familial support, value of vaccination, and autonomy) and elderly family members' age were correlated with caregiver intention. These factors should be considered in developing interventions to enhance caregivers' intentions to vaccinate their elderly family members with MNDs against COVID-19.

WITHDRAWN: Metformin alleviates inflammatory response and severity rate of COVID-19 infection in elderly individuals

ObjectiveTo evaluate the relationship between metformin and the outcome of COVID-19 infection. MethodsThe study included 413 patients with type 2 diabetes among the 5,217 patients enrolled in a COVID-19 study, and analyzed whether receiving metformin therapy prior to infection was associated with risk of ICU admission, development of pneumonia and length of hospital stay. The study also examined the correlation between metformin treatment and levels of IL-6, CRP, SF, L, CD4 at admission, as well as the increase in ORF1abCT after one week of hospitalization. ResultsThere were no differences in age, sex, BMI, comorbidities, number of vaccine doses or eGFR between patients receiving and not receiving metformin therapy. In the ICU group, the proportion of patients not receiving metformin was 92.5%, significantly higher than the 69.2% of patients not admitted to ICU (p=0.010). In the pneumonia group, the proportion of patients not receiving metformin was 78.6%, significantly higher than the 67.2% in the non-pneumonia group (p=0.020). Compared with patients receiving no treatment, those receiving metformin had a shorter hospital stay (12.1±5.9 days vs. 14.5±8.2 days, p=0.001). In the patients ≥60 years old, those receiving treatment had significantly lower levels of IL-6 (median, 12.3 pg/ml vs. 4.0 pg/ml, p=0.026) and significantly higher levels of Lymphocyte (median, 1.2×109/L vs. 1.4×109/L, p=0.015) compared with those not receiving treatment. However, for the patients under 60, there were no significant differences observed in IL-6 and Lymphocyte levels between those receiving treatment and those not. Conclusionmetformin can reduce the severity of COVID-19 infection and attenuate the inflammatory response associated with COVID-19 infection.

Distinct SARS-CoV-2 specific NLRP3 and IL-1β responses in T cells of aging patients during acute COVID-19 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19) that presents with varied clinical manifestations ranging from asymptomatic or mild infections and pneumonia to severe cases associated with cytokine storm, acute respiratory distress syndrome (ARDS), and even death. The underlying mechanisms contributing to these differences are unclear, although exacerbated inflammatory sequelae resulting from infection have been implicated. While advanced aging is a known risk factor, the precise immune parameters that determine the outcome of SARS-CoV-2 infection in elderly individuals are not understood. Here, we found aging-associated (age ≥61) intrinsic changes in T cell responses when compared to those from individuals aged ≤ 60, even among COVID-positive patients with mild symptoms. Specifically, when stimulated with SARS-CoV-2 peptides in vitro, peripheral blood mononuclear cell (PBMC) CD4+ and CD8+ T cells from individuals aged ≥61 showed a diminished capacity to produce IFN-γ and IL-1β. Although they did not have severe disease, aged individuals also showed a higher frequency of PD-1+ cells and significantly diminished IFN-γ/PD-1 ratios among T lymphocytes upon SARS-CoV-2 peptide stimulation. Impaired T cell IL-1β expression coincided with reduced NLRP3 levels in T lymphocytes. However, the expression of these molecules was not affected in the monocytes of individuals aged ≥61. Together, these data reveal SARS-CoV-2-specific CD4+ and CD8+ T-cell intrinsic cytokine alterations in the individuals older than 61 and may provide new insights into dysregulated COVID-directed immune responses in the elderly.

The Course of Diabetic Foot Infection in Elderly Patients: Data of Patients From Turkey.

With the aging population, it is expected that diabetes and related complications will increase rapidly. The aim of this study was to examine the signs and symptoms of diabetic foot infection in elderly individuals. Patients with diabetic foot infection were grouped as mild, moderate, and severe. Patients aged <65 years and those who did not meet the diagnosis of diabetic foot infection were excluded from the study. Only the first applications of patients who applied to the hospital multiple times with diabetic foot infection diagnosis were evaluated. 314 patients were included in the study. The mean age of the patients was 71.5 (±12). The number of patients aged 75 and over was 125 (39.8%). Of the patients, 25.7% had mild, 61.7% moderate, and 12.4% severe clinical forms. 131 (41.7%) of the patients had osteomyelitis. Amputation was performed in 112 of the patients. Antibiotic treatment was given to 102 patients only. While 89 patients died, a significant correlation was found between all groups between amputation rate and mortality frequency and clinical severity of diabetic foot infection (P < .001). In our study, it was observed that the clinical severity of diabetic foot infection was more severe and the overall mortality rate was higher in geriatric patients. In light of all these data, it can be concluded that an early and comprehensive roadmap should be followed in geriatric patients with diabetic foot infection who have an increased risk of morbidity and mortality.

Intranasal immunization with HRSV prefusion F protein and CpG adjuvant elicits robust protective effects in mice

Human respiratory syncytial virus (HRSV) is a leading cause of lower respiratory tract infections in elderly individuals and young children/infants and can cause bronchiolitis and even death. There is no licensed HRSV vaccine. An ideal vaccine should induce high titers of neutralizing antibodies and a Th1-biased immune response. In this study, we used EXPI293 cells to express the fusion (F) protein with a prefusion conformation (PrF) and compared the safety and efficacy of intranasal immunization with PrF in combination with two mucosal adjuvants (CpG ODN and liposomes) in mice. After two intranasal administrations, mice in the PrF + CpG group produced high titers of neutralizing antibodies (4961) and a Th1-biased immune response compared with the PrF + Lipo group. The lung viral load of mice in the PrF + CpG group was significantly reduced (3.5 log) compared with that in the adjuvant control group, and the survival rate was 100 %, while the survival rate of mice in the PrF + Lipo group was only 67 %. At the same time, this immunization strategy reduced the pathological damage to the lungs in mice. In conclusion, the combination of PrF and CpG adjuvant is immunogenic, elicits a Th1 type immune response, and completely protects mice from a lethal HRSV challenge. It is worthy of further evaluation as an HRSV vaccine in clinical trials.Clinical trial registration.This study was not related to human participation or experimentation.

Germline rare variants of lectin pathway genes predispose to asymptomatic SARS-CoV-2 infection in elderly individuals

PurposeEmerging evidence suggest that infection-dependent hyperactivation of complement system (CS) may worsen COVID-19 outcome. We investigated the role of predicted high impact rare variants — referred as qualifying variants (QVs) — of CS genes in predisposing asymptomatic COVID-19 in elderly individuals, known to be more susceptible to severe disease. MethodsExploiting exome sequencing data and 56 CS genes, we performed a gene-based collapsing test between 164 asymptomatic subjects (aged ≥60 years) and 56,885 European individuals from the Genome Aggregation Database. We replicated this test comparing the same asymptomatic individuals with 147 hospitalized patients with COVID-19. ResultsWe found an enrichment of QVs in 3 genes (MASP1, COLEC11, and COLEC10), which belong to the lectin pathway, in the asymptomatic cohort. Analyses of complement activity in serum showed decreased activity of lectin pathway in asymptomatic individuals with QVs. Finally, we found allelic variants associated with asymptomatic COVID-19 phenotype and with a decreased expression of MASP1, COLEC11, and COLEC10 in lung tissue. ConclusionThis study suggests that genetic rare variants can protect from severe COVID-19 by mitigating the activity of lectin pathway and prothrombin. The genetic data obtained through ES of 786 asymptomatic and 147 hospitalized individuals are publicly available at http://espocovid.ceinge.unina.it/

Vaccination With a Latch Peptide Provides Serotype-Independent Protection Against Group B Streptococcus Infection in Mice

Streptococcus agalactiae (group B streptococcus [GBS]) is a leading cause of invasive diseases in neonates and severe infections in elderly individuals. GBS serine-rich repeat glycoprotein 1 (Srr1) acts as a critical virulence factor by facilitating GBS invasion into the central nervous system through interaction with the fibrinogen Aα chain. This study revealed that srr1 is highly conserved, with 86.7% of GBS clinical isolates expressing the protein. Vaccination of mice with different Srr1 truncated peptides revealed that only Srr1 truncates containing the latch domain protected against GBS meningitis. Furthermore, the latch peptide alone was immunogenic and elicited protective antibodies, which efficiently enhanced antibody-mediated opsonophagocytic killing of GBS by HL60 cells and provided heterogeneous protection against 4 different GBS serogroups. Taken together, these findings indicated that the latch domain of Srr1 may constitute an effective peptide vaccine candidate for GBS.

Respiratory infection promotes T cell infiltration and amyloid-β deposition in APP/PS1 mice

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by deposits of amyloid-β and neurofibrillary tangles. It has been suggested that inflammatory changes are associated with disease; however, it has not been established whether these are a consequence of ongoing neurodegeneration or whether inflammation itself contributes to disease pathogenesis. Recent studies suggest that exposure to infection can accelerate cognitive decline in AD patients, and pathogens have been detected in the AD brain. However, the influence of infection on neuroinflammation and pathology remains poorly understood. In this study, we examined the effect of a peripheral infection on AD pathology in APP/PS1 mice. We found that, 8 weeks after infection with the Gram negative respiratory pathogen Bordetella pertussis, there was significant infiltration of IFNγ- and IL-17–producing T cells and NKT cells in older APP/PS1 mice. This was accompanied by increased glial activation and amyloid-β deposition. The data suggest that infection is a critical factor in the progression of AD, emphasising the importance of early diagnosis and treatment of infections in elderly individuals.

Prevalence and factors associated with HCV infection among elderly individuals in a southern Brazilian city

Few Latin American studies have assessed the prevalence of hepatitis C virus (HCV) infection in elderly individuals, in whom the highest rates are expected. We aimed to investigate the prevalence of and factors associated with HCV infection in elderly residents in the municipality of Tubarão, Santa Catarina. This cross-sectional study included 820 individuals (aged ≥ 60 years) who were selected by simple random sampling. The presence of anti-HCV antibodies was tested by chemiluminescence, and HCV RNA detection was performed for the anti-HCV-reactive subjects. Those individuals who were anti-HCV reactive but had undetectable HCV RNA levels were tested using a third-generation recombinant immunoblot assay. The variables were compared using the chi-squared test or Fisher's exact test, and those variables with p < 0.05 were included in the logistic regression model. The mean patient age was 68.6 years (SD 7.0 years); 39% were men, and 92% were Caucasian. Eighteen subjects were anti-HCV positive. Among these individuals, 4 were characterized as false-positives, leaving 14 (1.7%) individuals with confirmed infections for analysis. HCV infection was associated with an age older than 65 years, households with 3 or more residents and the previous transfusion of blood products. In the logistic regression analysis, the following variables were independently associated with HCV infection: households with 3 or more residents (OR 7.9, 95% CI 1.7-35.9, p = 0.008) and previous blood transfusion (OR 6.2, 95% CI 2.1-18.6, p = 0.001). The HCV prevalence in the elderly population in the municipality of Tubarão was higher than that found in previous studies of blood donors in the same region. Although exposure to contaminated blood products remained important, other transmission routes, such as household transmission, could play a role in HCV infection.

Serological prevalence of hepatitis B virus and hepatitis C virus infection in the elderly population

The hepatitis B virus (HBV) and hepatitis C virus (HCV) infections may seriously affect survival rate. The median length of life in developed countries is increasing and the elderly may be considered as an epidemiologically distinct group due to higher whole-life risk of blood-borne viral infections. To determine the seroprevalence of HBV and HCV infections in elderly individuals participating in a Polish nationwide survey - PolSenior. A total of 4979 individuals aged 65 years and older were asked about past or present viral hepatitis, and a blood test was carried out for HBsAg and anti-HCV antibodies in 3826 individuals. The respondents were divided into six age groups of equal size: 65-69, 70-74, 75-79, 80-84, 85-89, and 90+ years. Past or present diagnosis of viral hepatitis was reported by 176 individuals (3.58%) and its prevalence was significantly most common in urban than in rural residents (4.02 vs. 2.92%; P=0.04). In multivariate analysis, only the job category was a significant variable (P=0.01) for the occurrence of viral hepatitis [most frequently in white-collar workers (3.56%) and least frequently in agricultural workers (1.47%)]. The overall prevalence of a positive HBsAg test was 1.12% (n=43) and that of an anti-HCV test was 2.93% (n=112). Only 12 anti-HCV-positive patients (10.7%) were aware of infection. Multivariate analyses did not indicate significant effects of age, sex, alcohol consumption, nutrition, marital or economic status, educational level, and site of residence on the incidence of HBV and HCV infections. HBsAg was associated with higher serum levels of aspartate aminotransferase, and anti-HCV with higher levels of aspartate aminotransferase and alanine aminotransferase. In elderly individuals, the seroprevalence of HBsAg is lower and the seroprevalence of anti-HCV is considerably higher than that in the general Polish population. The former may have been because of increased mortality from HBV-related complications and the latter of increased whole-life risk of infection. Programs for screening of elderly individuals for occult HCV infection should be considered.

Clinical decision‐making process for early nonspecific signs of infection in institutionalised elderly persons: experience of nursing assistants

To illuminate nursing assistant's experiences of the clinical decision-making process when they suspect that a resident has an infection and how their process relates to other professions. The assessment of possible infection in elderly individuals is difficult and contributes to a delayed diagnosis and treatment, worsening the goal of good care. Recently we explored that nursing assistants have a keen observational ability to detect early signs and symptoms that might help to confirm suspected infections early on. To our knowledge there are no published papers exploring how nursing assistants take part in the clinical decision-making process. Explorative, qualitative study. Community care for elderly people. Twenty-one nursing assistants, 22-61 years. Focus groups with verbatim transcription. The interviews were subjected to qualitative content analysis for manifest and latent content with no preconceived categories. The findings are described as a decision-making model consisting of assessing why a resident feels unwell, divided into recognition and formulation and strategies for gathering and evaluating information, influenced by personal experiences and preconceptions and external support system and, secondly, as taking action, consisting of reason for choice of action and action, influenced by feedback from the nurse and physician. Nursing assistant's assessment is based on knowing the resident, personal experiences and ideas about ageing. Nurses and physician's response to the nursing assistant's observations had a great impact on the latter's further action. A true inter-professional partnership in the clinical decision-making process would enhance the possibility to detect suspected infection early on, and thereby minimize the risk of delayed diagnosis and treatment and hence unnecessary suffering for the individual. In order to improve the clinical evaluation of the individual, and thereby optimise patient safety, it is important to involve nursing assistants in the decision-making process.

Influenza vaccination and risk of community-acquired pneumonia in immunocompetent elderly people: a population-based, nested case-control study

Pneumonia is a common complication of influenza infection in elderly individuals and could therefore potentially be prevented by influenza vaccination. In studies with data from administrative sources, vaccinated elderly people had a reduced risk of admission for pneumonia compared with unvaccinated seniors; however, these findings could have been biased by underlying differences in health between the groups. Furthermore, since most individuals with pneumonia are not treated in hospital, such studies should include both outpatient and inpatient events. We therefore assessed whether influenza vaccination is associated with a reduced risk of community-acquired pneumonia in immunocompetent elderly people after controlling for health status indicators. We did a population-based, nested case-control study in immunocompetent elderly people aged 65-94 years (cases and controls) enrolled in Group Health (a health maintenance organisation) during the 2000, 2001, and 2002 preinfluenza periods and influenza seasons. Cases were individuals with an episode of outpatient or inpatient community-acquired pneumonia (validated by review of medical records or chest radiograph reports). We randomly selected two age-matched and sex-matched controls for each case. The exposure of interest was influenza vaccination. We reviewed medical records to define potential confounders, including smoking history, presence and severity of lung and heart disease, and frailty indicators. 1173 cases and 2346 controls were included in the study. After we adjusted for the presence and severity of comorbidities, as defined by chart review, influenza vaccination was not associated with a reduced risk of community-acquired pneumonia (odds ratio 0.92, 95% CI 0.77-1.10) during the influenza season. The effect of influenza vaccination on the risk of pneumonia in elderly people during influenza seasons might be less than previously estimated. Group Health Center for Health Studies internal funds and Group Health Community Foundation fellowship grant.

Age‐Related Differences in Pulmonary Cytokine Response to Respiratory Syncytial Virus Infection: Modulation by Anti‐inflammatory and Antiviral Treatment

Respiratory syncytial virus (RSV) is the major cause of severe lower respiratory tract infection in infants and young children. Recently, RSV has also been recognized as a serious health risk in elderly individuals, but the pathogenesis of RSV infection in elderly individuals remains unknown. Dynamics of pulmonary cytokine response (including interferon- gamma , interleukin [IL]-4, IL-10, IL-6, monocyte chemoattractant protein-1, and growth-regulated oncogene [GRO] mRNA) during acute RSV infection were investigated in young (<2 months old) and aged (>9 months old) cotton rats (Sigmodon hispidus). Therapeutic treatments that diminish viral replication (antiviral antibody) and pulmonary inflammation (anti-inflammatory corticosteroid) in RSV-infected cotton rats were used to evaluate the contribution of virus replication and inflammation to the development of RSV disease with respect to age. The time of the peak expression of the majority of cytokines was shifted with respect to age. Antiviral and anti-inflammatory treatments had a similar effect on cytokine expression in aged and young cotton rats. GRO mRNA transcripts were more abundant in the lungs of aged cotton rats. The present study reports an age-related delay in the pulmonary cytokine response to RSV and an imbalance in chemokine production with respect to age and underscores different components of RSV pathogenesis with respect to their molecular signature.

Nutritional strategies to boost immunity and prevent infection in elderly individuals.

Older adults are at risk for malnutrition, which may contribute to their increased risk of infection. Nutritional supplementation strategies can reduce this risk and reverse some of the immune dysfunction associated with advanced age. This review discusses nutritional interventions that have been examined in clinical trials of older adults. The data support use of a daily multivitamin or trace-mineral supplement that includes zinc (elemental zinc, >20 mg/day) and selenium (100 microg/day), with additional vitamin E, to achieve a daily dosage of 200 mg/day. Specific syndromes may also be addressed by nutritional interventions (for example, cranberry juice consumption to reduce urinary tract infections) and may reduce antibiotic use in older adults, particularly those living in long-term care facilities. Drug-nutrient interactions are common in elderly individuals, and care providers should be aware of these interactions. Future research should evaluate important clinical end points rather than merely surrogate markers of immunity.

New records of nail and skin infection due toOnychocola canadensisand description of its teleomorphArachnomyces nodosetosussp. nov.

Non-dermatophytic fungi are increasingly being recognized as agents of onychomycosis. In 1990, three cases of chronic infection of the great toenail in adult female residents of Canada were attributed to Onychocola canadensis, a previously unknown hyphomycete. Three additional cases were suspicious but unconfirmed. This report documents seven new records, including six of toenail infection in elderly individuals and one case of glabrous skin infection. Three isolations from New Zealand represent the first report of O. canadensis outside Canada. Treatment with griseofulvin in one New Zealand hallux infection case was found to improve the appearance of the nail, but specimens were culture positive after 6 months. The development in culture of broad, brown, nodose, thick-walled hyphae suggested an affinity to the ascomycete genus Arachnomyces. Although mating experiments were attempted on several different media, ascocarps were produced in six mated pairs on sterilized rice grains or rice extract agar after 7-12 months incubation. Arachnomyces nodosetosus Sigler & Abbott sp. nov. is described and compared with Arachnomyces minimus Malloch & Cain, also rarely isolated from cutaneous specimens. The genus Arachnomyces is placed in the Gymnoascaceae (Onygenales).

Plasma lactoferrin as a marker of infection in elderly individuals.

To assess lactoferrin as a marker of infection, plasma lactoferrin (LF) levels were determined in elderly in patients with infection and compared with age- and sex-matched healthy and hospital controls and young healthy blood donors. The median LF level in infection (800 ng/mL) was significantly higher than in healthy elderly living in old people's home (300 ng/mL) or elderly hospital controls (298 ng/mL) (p less than 0.01 in each case). Plasma LF correlated significantly with elastase alpha-1-proteinase inhibitor complex (EPIC) (Rs = 0.8, p less than 0.01) and C-reactive protein (CRP) (Rs = 0.45, p less than 0.02), but not with erythrocyte sedimentation rate (ESR) or white blood cell counts. We conclude that plasma LF, like CRP and EPIC, is a marker of infection in elderly individuals.