Invasive meningococcal disease in older adults: current perspectives and call for action.

PURPOSE: Invasive meningococcal disease (IMD) is a devastating condition. While most attention is directed towards disease in children and adolescents, IMD poses an important cause of morbidity and mortality in adults ≥60 years. While immunization is a critical component of healthy ageing strategies, meningococcal immunization is not routinely offered to older adults. The aim of this review was to summarize clinical and epidemiological aspects of IMD and available immunization strategies, with a particular focus on disease in older individuals, to emphasize the importance of this rather neglected area. METHODS: An expert working group was established to evaluate clinical and epidemiological data to raise awareness of IMD in older individuals, and develop suggestions to improve the existing burden. RESULTS: Routine child and adolescent meningococcal immunization has substantially reduced IMD in these targeted populations. Consequently, prevalence and proportion of IMD among those ≥60 years, mostly unvaccinated, is increasing in developed countries (accounting for up to 25% of cases). IMD-related mortality is highest in this age-group, with substantial sequelae in survivors. IMD due to serogroups W and Y is more prevalent among older adults, often with atypical clinical features (pneumonia, gastrointestinal presentations) which may delay timely treatment. CONCLUSIONS: IMD in older adults remains overlooked and greater awareness is required at clinical and societal levels. We encourage clinicians and immunization policy makers to reconsider IMD, with a call for action to remedy existing inequity in older adult access to protective meningococcal immunization.

Vascular Aging and Atherosclerosis: A Perspective on Aging.

Vascular aging (VA) is recognized as a pivotal factor in the development and progression of atherosclerosis (AS). Although various epidemiological and clinical research has demonstrated an intimate connection between aging and AS, the candidate mechanisms still require thorough examination. This review adopts an aging-centric perspective to deepen the comprehension of the intricate relationship between biological aging, vascular cell senescence, and AS. Various aging-related physiological factors influence the physical system's reactions, including oxygen radicals, inflammation, lipids, angiotensin II, mechanical forces, glucose levels, and insulin resistance. These factors cause endothelial dysfunction, barrier damage, sclerosis, and inflammation for VA and promote AS via distinct or shared pathways. Furthermore, the increase of senescent cells inside the vascular tissues, caused by genetic damage, dysregulation, secretome changes, and epigenetic modifications, might be the primary cause of VA.

The forecasted prevalence of comorbidities and multimorbidity in people with HIV in the United States through the year 2030: A modeling study.

BACKGROUND: Estimating the medical complexity of people aging with HIV can inform clinical programs and policy to meet future healthcare needs. The objective of our study was to forecast the prevalence of comorbidities and multimorbidity among people with HIV (PWH) using antiretroviral therapy (ART) in the United States (US) through 2030. METHODS AND FINDINGS: Using the PEARL model-an agent-based simulation of PWH who have initiated ART in the US-the prevalence of anxiety, depression, stage ≥3 chronic kidney disease (CKD), dyslipidemia, diabetes, hypertension, cancer, end-stage liver disease (ESLD), myocardial infarction (MI), and multimorbidity (≥2 mental or physical comorbidities, other than HIV) were forecasted through 2030. Simulations were informed by the US CDC HIV surveillance data of new HIV diagnosis and the longitudinal North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) data on risk of comorbidities from 2009 to 2017. The simulated population represented 15 subgroups of PWH including Hispanic, non-Hispanic White (White), and non-Hispanic Black/African American (Black/AA) men who have sex with men (MSM), men and women with history of injection drug use and heterosexual men and women. Simulations were replicated for 200 runs and forecasted outcomes are presented as median values (95% uncertainty ranges are presented in the Supporting information). In 2020, PEARL forecasted a median population of 670,000 individuals receiving ART in the US, of whom 9% men and 4% women with history of injection drug use, 60% MSM, 8% heterosexual men, and 19% heterosexual women. Additionally, 44% were Black/AA, 32% White, and 23% Hispanic. Along with a gradual rise in population size of PWH receiving ART-reaching 908,000 individuals by 2030-PEARL forecasted a surge in prevalence of most comorbidities to 2030. Depression and/or anxiety was high and increased from 60% in 2020 to 64% in 2030. Hypertension decreased while dyslipidemia, diabetes, CKD, and MI increased. There was little change in prevalence of cancer and ESLD. The forecasted multimorbidity among PWH receiving ART increased from 63% in 2020 to 70% in 2030. There was heterogeneity in trends across subgroups. Among Black women with history of injection drug use in 2030 (oldest demographic subgroup with median age of 66 year), dyslipidemia, CKD, hypertension, diabetes, anxiety, and depression were most prevalent, with 92% experiencing multimorbidity. Among Black MSM in 2030 (youngest demographic subgroup with median age of 42 year), depression and CKD were highly prevalent, with 57% experiencing multimorbidity. These results are limited by the assumption that trends in new HIV diagnoses, mortality, and comorbidity risk observed in 2009 to 2017 will persist through 2030; influences occurring outside this period are not accounted for in the forecasts. CONCLUSIONS: The PEARL forecasts suggest a continued rise in comorbidity and multimorbidity prevalence to 2030, marked by heterogeneities across race/ethnicity, gender, and HIV acquisition risk subgroups. HIV clinicians must stay current on the ever-changing comorbidities-specific guidelines to provide guideline-recommended care. HIV clinical directors should ensure linkages to subspecialty care within the clinic or by referral. HIV policy decision-makers must allocate resources and support extended clinical capacity to meet the healthcare needs of people aging with HIV.

Meningococcal disease in the Middle East: A report from the Global Meningococcal Initiative.

This review details recent findings from the Global Meningococcal Initiative's (GMI) recent meeting on the surveillance and control strategies for invasive meningococcal disease in the Middle East. The nature of case reporting and notification varies across the region, with many countries using bacterial meningitis as an IMD case definition in lieu of meningitis and septicaemia. This may overlook a significant burden associated with IMD leading to underreporting or misreporting of the disease. Based on these current definitions, IMD reported incidence remains low across the region, with historical outbreaks mainly occurring due to the Hajj and Umrah mass gatherings. The use of case confirmation techniques also varies in Middle Eastern countries. While typical microbiological techniques, such as culture and Gram staining, are widely used for characterisation, polymerase chain reaction (PCR) testing is utilised in a small number of countries. PCR testing may be inaccessible for several reasons including sample transportation, cost, or a lack of laboratory expertise. These barriers, not exclusive to PCR use, may impact surveillance systems more broadly. Another concern throughout the region is potentially widespread ciprofloxacin resistance since its use for chemoprophylaxis remains high in many countries.

Attenuation of allergen-specific immunotherapy for atopic dermatitis by ectopic colonization of Brevundimonas vesicularis in the intestine.

Allergen-specific immunotherapy (AIT) has shown beneficial effects against atopic dermatitis (AD); however, the mechanisms and parameters underlying the efficacy of AIT remain unclear. Here, we report that the community structure and function of the oral and gut microbiota are changed in patients with AD undergoing AIT. Transplantation of fecal microbiota from patients who respond well to AIT improves AD-like dermatitis in mice. The abundance of Brevundimonas vesicularis in the gut of AD patients has been found to be positively correlated with disease severity and is decreased following AIT. Furthermore, we find that B. vesicularis from the oral cavity might ectopically colonize the gut of AD patients. In AD model mice, meanwhile, B. vesicularis promotes the skewing of the Treg/Th17 balance toward Th17 polarization and attenuates the efficacy of ovalbumin-specific immunotherapy. Our findings provide potential strategies for the optimization of AIT for AD via the modulation of the gut microbiota.

Risk of long COVID main symptoms after SARS-CoV-2 infection: a systematic review and meta-analysis.

This review aimed to summarise the relative risk (RR) of the main symptoms of long COVID in people infected with SARS-CoV-2 compared to uninfected controls, as well as the difference in health-related quality of life (HRQoL) after infection. MEDLINE, EMBASE, PubMed, NLM-LitCovid, WHO-COVID-19, arXiv and Europe-PMC were searched up to 23rd March 2022. Studies reporting risk (four or more weeks after infection) of fatigue, shortness of breath, and cognitive dysfunction, as well as comparative HRQoL outcomes, were included. Pairwise random-effects meta-analyses were performed to pool risks of individual symptoms. Thirty-three studies were identified; twenty studies reporting symptom risks were included in the meta-analyses. Overall, infection with SARS-CoV-2 carried significantly higher risk of fatigue (RR 1.72, 95% confidence intervals [CIs] 1.41, 2.10), shortness of breath (RR 2.60, 95% CIs 1.96, 3.44), memory difficulties (RR 2.53, 95% CIs 1.30, 4.93), and concentration difficulties (RR 2.14, 95% CIs 1.25, 3.67). Quality of life findings were varied and comparisons between studies were challenging due to different HRQoL instruments used and study heterogeneity, although studies indicated that severe hospitalised COVID is associated with a significantly poorer HRQoL after infection. These risks are likely to constantly change as vaccines, reinfections, and new variants alter global immunity.

The intersection of biological sex and gender in adverse events following seasonal influenza vaccination in older adults.

BACKGROUND: Women/females report more adverse events (AE) following immunization than men/males for many vaccines, including the influenza and COVID-19 vaccines. This discrepancy is often dismissed as a reporting bias, yet the relative contributions of biological sex and gender are poorly understood. We investigated the roles of sex and gender in the rate of AE following administration of the high-dose seasonal influenza vaccine to older adults (≥ 75 years) using an AE questionnaire administered 5-8 days post-vaccination. Participant sex (male or female) was determined by self-report and a gender score questionnaire was used to assign participants to one of four gender categories (feminine, masculine, androgynous, or undifferentiated). Sex steroid hormones and inflammatory cytokines were measured in plasma samples collected prior to vaccination to generate hypotheses as to the biological mechanism underpinning the AE reported. RESULTS: A total of 423 vaccines were administered to 173 participants over four influenza seasons (2019-22) and gender data were available for 339 of these vaccinations (2020-22). At least one AE was reported following 105 vaccinations (25%), by 23 males and 82 females. The majority of AE occurred at the site of injection, were mild, and transient. The odds of experiencing an AE were 3-fold greater in females than males and decreased with age to a greater extent in females than males. The effects of gender, however, were not statistically significant, supporting a central role of biological sex in the occurrence of AE. In males, estradiol was significantly associated with IL-6 and with the probability of experiencing an AE. Both associations were absent in females, suggesting a sex-specific effect of estradiol on the occurrence of AE that supports the finding of a biological sex difference. CONCLUSIONS: These data support a larger role for biological sex than for gender in the occurrence of AE following influenza vaccination in older adults and provide an initial investigation of hormonal mechanisms that may mediate this sex difference. This study highlights the complexities of measuring gender and the importance of assessing AE separately for males and females to better understand how vaccination strategies can be tailored to different subsets of the population.

Immunogenicity and safety of quadrivalent influenza vaccine among young and older adults in Tianjin, China: implication of immunosenescence as a risk factor.

BACKGROUND: Older adults are more vulnerable to seasonal influenza than younger adults. The immune responses of older persons to the influenza vaccine are usually poorer than those of young individuals, which is hypothesized due to immunosenescence. We conducted a study to evaluate the immunogenicity and safety of a quadrivalent inactivated influenza vaccine (IIV4) in a total of 167 young (< 65 years, n = 79) and older (≥ 65 years, n = 88) adults from October 2021 to March 2022 in Tianjin, China. A single dose was administered to all participants. Blood samples were collected and strain-specific hemagglutination inhibition (HAI) antibody titers were measured before and 21 to 28 days after vaccination. Safety information was also collected for 28 days and 6 months after vaccination. Differences in immunogenicity and safety were compared between young and old age groups, and multivariate logistic regression was used to estimate the effect of age and other factors on HAI antibody responses. RESULTS: Overall, geometric mean titers (GMTs) against all four vaccine strains in older adults were lower than those in the young, whereas the seroconversion rates (SCRs) were similar. Multivariate logistic regression analysis showed that age, influenza vaccination history, and pre-vaccination HAI titers were independent factors affecting SCRs and seroprotection rates (SCRs). Older age had significant negative impact on SCRs against H1N1 (OR, 0.971; 95% CI: 0.944-0.999; P = 0.042) and B/Victoria (OR, 0.964; 95% CI: 0.937-0.992; P = 0.011). In addition, there was a significant negative correlation between chronological age (years) and post-vaccination HAI titers against H1N1 (rho = -0.2298, P < 0.0001), B/Victoria (rho = -0.2235, P = 0.0037), and B/Yamagata (rho = -0.3689, P < 0.0001). All adverse events were mild (grade 1 or grade 2) that occurred within 28 days after vaccination, and no serious adverse event was observed. CONCLUSIONS: IIV4 is immunogenic and well-tolerated in young and older adults living in Tianjin, China. Our findings also indicate that age is an independent factor associated with poorer humoral immune responses to IIV4.

Interseason waning of vaccine-induced hemagglutination inhibition antibody titers and contributing factors to pre-existing humoral immunity against influenza in community-dwelling older adults 75 years and older.

BACKGROUND: Seasonal influenza causes significant morbidity and mortality with a disproportionately high disease burden in older adults. Strain-specific hemagglutination-inhibition (HAI) antibody titer is a well-established measure of humoral immunity against influenza and pre-vaccination HAI titer is a valuable indicator of pre-existing humoral immunity at the beginning of each influenza season in highly vaccinated older adults. While vaccine-induced HAI antibody titers are known to wane over time, accurate assessment of their interseason waning has been challenging. This is because pre-vaccination HAI titers are routinely measured using current season vaccine strain antigens instead of the prior season vaccines with which individuals were immunized; as such, they do not accurately represent residual antibody titers from prior season vaccination. This study took advantage of available pre-vaccination HAI titers measured using both current and prior season vaccine strain antigens in a longitudinal influenza immunization study with participants enrolled for multiple consecutive influenza seasons from 2014 through 2017. Influenza A virus (IAV) H3N2 and influenza B virus (IBV) strains in the vaccine formula changed in 2015 and again in 2016 season. IAV H1N1 vaccine strain remained the same from 2014 through 2016 seasons, but changed in 2017. We also investigated factors contributing to pre-existing humoral immunity. RESULTS: Interseason waning of HAI titers was evident, but rates of waning varied among vaccine strains and study seasons, from 18% (p = .43) to 61% (p < .01). Rates of waning were noticeably greater when pre-vaccination HAI titers were measured by the routine approach, i.e., using current season vaccine strain antigens, from 33% (p = .12) to 83% (p < .01), adjusting for age at prior study season, sex, race, and education. This was largely because the routinely measured pre-vaccination HAI titers underrepresented residual HAI titers from prior season vaccinations. Moreover, interseason antibody waning and prior season post-vaccination HAI titers had significant and independent associations with pre-vaccination HAI titers. CONCLUSIONS: The routinely measured pre-vaccination HAI titer overestimates interseason HAI antibody waning as it underestimates residual antibody titers from prior season vaccination when virus strains in the vaccine formula change. Moreover, interseason antibody waning and prior season post-vaccination HAI titers independently contribute to pre-existing humoral immunity in this highly vaccinated, community-dwelling older adult population.

Antiviral effect and mechanism of Phillyrin and its reformulated FS21 against influenza.

Background: Influenza virus causes significant morbidity and mortality with pandemic threat. Oleaceae Fructus Forsythiae is a medicinal herb. This study aimed to investigate antiviral effect of Phillyrin, a purified bioactive compound from this herb, and its reformulated preparation FS21 against influenza and its mechanism. Methods: Madin-Darby Canine Kidney (MDCK) cells were infected by one of six influenza viruses: five influenza A viruses (IAVs: three H1N1 and two H3N2) and one influenza B virus (IBV). Virus-induced cytopathic effects were observed and recorded under microscope. Viral replication and mRNA transcription were evaluated by quantitative polymerase chain reaction (qPCR) and protein expression by Western blot. Infectious virus production was assessed using TCID50 assay, and IC50 was calculated accordingly. Pretreatment and time-of-addition experiments with Phillyrin or FS21 added 1 h before or in early (0-3 h), mid (3-6 h), or late (6-9 h) stages of viral infection were performed to assess their antiviral effects. Mechanistic studies included hemagglutination and neuraminidase inhibition, viral binding and entry, endosomal acidification, and plasmid-based influenza RNA polymerase activity. Results: Phillyrin and FS21 had potent antiviral effects against all six IAV and IBV in a dose-dependent manner. Mechanistic studies showed that both suppressed influenza viral RNA polymerase with no effect on virus-mediated hemagglutination inhibition, viral binding or entry, endosomal acidification, or neuraminidase activity. Conclusions: Phillyrin and FS21 have broad and potent antiviral effects against influenza viruses with inhibition of viral RNA polymerase as the distinct antiviral mechanism.

The intersection of biological sex and gender in adverse events following seasonal influenza vaccination in older adults.

Background Women/females report more adverse events (AE) following immunization than men/males for many vaccines, including the influenza and COVID-19 vaccines. This discrepancy is often dismissed as a reporting bias, yet the relative contributions of biological sex and gender are poorly understood. We investigated the roles of sex and gender in the rate of AE following administration of the high-dose seasonal influenza vaccine to older adults (≥ 75 years) using an AE questionnaire administered 5-8 days post-vaccination. Participant sex (male or female) was determined by self-report and a gender score questionnaire was used to assign participants to one of four gender categories (feminine, masculine, androgynous, or undifferentiated). Sex steroid hormones and inflammatory cytokines were measured in plasma samples collected prior to vaccination to elucidate a possible biological mechanism for the AE reported. Results A total of 423 vaccines were administered to 173 participants over four influenza seasons (2019-22) and gender data were available for 339 of these vaccinations (2020-22). At least one AE was reported following 105 vaccinations (25%), by 23 males and 82 females. The majority of AE occurred at the site of injection, were mild, and transient. The odds of experiencing an AE were 3-fold greater in females than males and decreased with age to a greater extent in females than males. The effects of gender, however, were not statistically significant, supporting a central role of biological sex in the occurrence of AE. In males, estradiol was significantly associated with IL-6 and with the probability of experiencing an AE. Both associations were absent in females, suggesting a sex-specific effect of estradiol on the occurrence of AE that supports the finding of a biological sex difference. Conclusions These data support a larger role for biological sex than for gender in the occurrence of AE following influenza vaccination in older adults and provide an initial investigation of hormonal mechanisms that may mediate this sex difference. This study highlights the complexities of measuring gender and the importance of assessing AE separately for males and females to better understand how vaccination strategies can be tailored to different subsets of the population.

Cancer-cell-derived sialylated IgG as a novel biomarker for predicting poor pathological response to neoadjuvant therapy and prognosis in pancreatic cancer.

BACKGROUND: Neoadjuvant therapy (NAT) is increasingly applied in pancreatic ductal adenocarcinoma (PDAC); however, accurate prediction of therapeutic response to NAT remains a pressing clinical challenge. Cancer-cell-derived sialylated immunoglobulin G (SIA-IgG) was previously identified as a prognostic biomarker in PDAC. This study aims to explore whether SIA-IgG expression in treatment-naïve fine needle aspirate (FNA) biopsy specimens could predict the pathological response (PR) to NAT for PDAC. METHODS: Endoscopic ultrasonography-guided FNA biopsy specimens prior to NAT were prospectively obtained from 72 patients with PDAC at the Johns Hopkins Hospital. SIA-IgG expression of PDAC specimens was assessed by immunohistochemistry. Associations between SIA-IgG expression and PR, as well as patient prognosis, were analyzed. A second cohort enrolling surgically resected primary tumor specimens from 79 patients with PDAC was used to validate the prognostic value of SIA-IgG expression. RESULTS: SIA-IgG was expressed in 58.3% of treatment-naïve FNA biopsies. Positive SIA-IgG expression at diagnosis was associated with unfavorable PR and can serve as an independent predictor of PR. The sensitivity and specificity of SIA-IgG expression in FNA specimens in predicting an unfavorable PR were 63.9% and 80.6%, respectively. Both positive SIA-IgG expression in treatment-naïve FNA specimens and high SIA-IgG expression in surgically resected primary tumor specimens were significantly associated with shorter survival. CONCLUSIONS: Assessment of SIA-IgG on FNA specimens prior to NAT may help predict PR for PDAC. Additionally, SIA-IgG expression in treatment-naïve FNA specimens and surgically resected primary tumor specimens were predictive of the prognosis for PDAC.

The intersection of gender and race in older adults' decision to receive COVID-19 vaccines.

COVID-19 vaccines are essential public health tools for protecting older adults, who are at high risk of severe outcomes associated with COVID-19. Little is known, however, about how older adults approach the decision to receive a COVID-19 vaccine. We hypothesized that intersections between gender and race may provide unique insight into the decision-making process and the factors that lead to vaccine uptake among hesitant individuals. We performed in-depth interviews with 24 older adults who had been vaccinated against COVID-19 and used the framework approach with an intersectional lens to analyze data. Two typologies emerged: eager compliers did not question the need to vaccinate, whereas hesitant compliers were skeptical of the vaccine and underwent a thorough decision-making process prior to vaccination. For eager compliers, the vaccine offered protection from a disease that posed a serious threat, and few risks were perceived. In contrast, hesitant compliers perceived risks associated with the vaccine product or mistrusted the infrastructure that led to rapid vaccine development. Hesitancy was greater among Black participants, and only Black participants reported mistrust in vaccine infrastructure. At the intersection of gender and race, a 'White male effect' was observed, whereby White men perceived the fewest risks associated with the vaccine, and Black women were the most fearful of serious side effects. Nearly all hesitant compliers ultimately got vaccinated due to the threat of COVID-19. Convenient access through vaccine clinics in senior's buildings was pivotal for hesitant compliers and external and internal influences had differential impacts by race and gender. Emphasizing the risk of COVID-19, convenient and accessible opportunities for vaccination, and messages that are targeted to specific groups are likely to increase vaccine uptake among older adults.

Investigating adolescent mental health of Chinese students during the COVID-19 pandemic: Multicenter cross-sectional comparative investigation.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has caused significant challenges for adolescent mental health. AIM: To survey adolescent students in China to determine the effects of the COVID-19 pandemic on their mental health. METHODS: A multicenter cross-sectional comparative investigation was conducted in March 2022. We collected demographic information and survey data related to the COVID-19 pandemic. The Patient Health Questionnaire-9 and Generalized Anxiety Disorder Screener scales were used for objective assessment of depression and anxiety. RESULTS: We collected mental health questionnaires from 3184 students. The investigation demonstrated that adolescents most strongly agreed with the following items: Increased time spent with parents, interference with academic performance, and less travel. Conversely, adolescents most strongly disagreed with the following items: Not having to go to school, feeling an increase in homework, and not socializing with people; 34.6% of adolescents were depressed before COVID-19, of which 1.9% were severely depressed. After COVID-19, 26.3% of adolescents were prone to depression, of which 1.4% were severely depressed. 24.4% of adolescents had anxiety before COVID-19, with severe anxiety accounting for 1.6%. After COVID-19, 23.5% of adolescents were prone to anxiety, of which 1.7% had severe anxiety. CONCLUSION: Chinese adolescents in different grades exhibited different psychological characteristics, and their levels of anxiety and depression were improved after the COVID-19 pandemic. Changes in educational management practices since the COVID-19 pandemic may be worth learning from and optimizing in long-term educational planning.

Ketogenic Diet: An Effective Treatment Approach for Neurodegenerative Diseases.

This review discusses the effects and mechanisms of a ketogenic diet on neurodegenerative diseases on the basis of available evidence. A ketogenic diet refers to a high-fat, mediumprotein, and low-carbohydrate diet that leads to a metabolic shift to ketosis. This review systematically summarizes the scientific literature supporting this effective treatment approach for neurodegenerative diseases, including effects on mitochondrial function, oxidative stress, neuronal apoptosis, neuroinflammation, and the microbiota-gut-brain axis. It also highlights the clinical evidence for the effects of the ketogenic diet in the treatment of Alzheimer's disease, Parkinson's disease, and motor neuron disease. Finally, it discusses the common adverse effects of ketogenic therapy. Although the complete mechanism of the ketogenic diet in the treatment of neurodegenerative diseases remains to be elucidated, its clinical efficacy has attracted many new followers. The ketogenic diet is a good candidate for adjuvant therapy, but its specific applicability depends on the type and the degree of the disease.

Roadmap for Sex-Responsive Influenza and COVID-19 Vaccine Research in Older Adults.

Sex differences in the immune system are dynamic throughout the lifespan and contribute to heterogeneity in the risk of infectious diseases and the response to vaccination in older adults. The importance of the intersection between sex and age in immunity to viral respiratory diseases is clearly demonstrated by the increased prevalence and severity of influenza and COVID-19 in older males compared to older females. Despite sex and age biases in the epidemiology and clinical manifestations of disease, these host factors are often ignored in vaccine research. Here, we review sex differences in the immunogenicity, effectiveness, and safety of the influenza and COVID-19 vaccines in older adults and the impact of sex-specific effects of age-related factors, including chronological age, frailty, and the presence of comorbidities. While a female bias in immunity to influenza vaccines has been consistently reported, understanding of sex differences in the response to COVID-19 vaccines in older adults is incomplete due to small sample sizes and failure to disaggregate clinical trial data by both sex and age. For both vaccines, a major gap in the literature is apparent, whereby very few studies investigate sex-specific effects of aging, frailty, or multimorbidity. By providing a roadmap for sex-responsive vaccine research, beyond influenza and COVID-19, we can leverage the heterogeneity in immunity among older adults to provide better protection against vaccine-preventable diseases.

Association of Frailty, Age, and Biological Sex With Severe Acute Respiratory Syndrome Coronavirus 2 Messenger RNA Vaccine-Induced Immunity in Older Adults.

BACKGROUND: Male sex and old age are risk factors for severe coronavirus disease 2019, but the intersection of sex and aging on antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has not been characterized. METHODS: Plasma samples were collected from older adults (aged 75-98 years) before and after 3 doses of SARS-CoV-2 mRNA vaccination, and from younger adults (aged 18-74 years) post-dose 2, for comparison. Antibody binding to SARS-CoV-2 antigens (spike protein [S], S receptor-binding domain, and nucleocapsid), functional activity against S, and live-virus neutralization were measured against the vaccine virus and the Alpha, Delta, and Omicron variants of concern (VOCs). RESULTS: Vaccination induced greater antibody titers in older females than in older males, with both age and frailty associated with reduced antibody responses in males but not females. Responses declined significantly in the 6 months after the second dose. The third dose restored functional antibody responses and eliminated disparities caused by sex, age, and frailty in older adults. Responses to the VOCs, particularly the Omicron variant, were significantly reduced relative to the vaccine virus, with older males having lower titers to the VOCs than older females. Older adults had lower responses to the vaccine and VOC viruses than younger adults, with greater disparities in males than in females. CONCLUSIONS: Older and frail males may be more vulnerable to breakthrough infections owing to low antibody responses before receipt of a third vaccine dose. Promoting third dose coverage in older adults, especially males, is crucial to protecting this vulnerable population.

Effects of 3 months of multi-nutrient supplementation on the immune system and muscle and respiratory function of older adults in aged care (The Pomerium Study): protocol for a randomised controlled trial.

INTRODUCTION: Immunosenescence leads to increased morbidity and mortality associated with viral infections and weaker vaccine responses. This has been well documented for seasonal influenza and the current pandemic with SARS-CoV-2 (COVID-19), which disproportionately impact older adults, particularly those in residential aged care facilities. Inadequate nutrient intakes associated with impaired immunity, respiratory and muscle function are likely to augment the effects of immunosenescence. In this study, we test whether the impact of inadequate nutrition can be reversed using multi-nutrient supplementation, consequently enhancing vaccine responses, reducing the risk of viral infections and improving respiratory and muscle function. METHODS AND ANALYSIS: The Pomerium Study is a 3-month, single-blind, randomised, controlled trial testing the effects of two daily servings of an oral multi-nutrient supplement (330 kcal, 20 g protein, 1.5 g calcium 3-hydroxy-3-methylbutyrate monohydrate (CaHMB), 449 mg calcium, 500 IU vitamin D3 and 25 vitamins and minerals) on the immune system and muscle and respiratory function of older adults in aged care in Melbourne, Australia. 160 older adults (≥75 years old) will be recruited from aged care facilities and randomised to treatment (multi-nutrient supplement) or control (usual care). The primary outcome is a change in T-cell subsets CD8 + and CD28null counts at months 1 and 3. Secondary outcomes measured at baseline and month 3 are multiple markers of immunosenescence (also at 1 month), body composition (bioimpedance), handgrip strength (dynamometer), physical function (short physical performance battery), respiratory function (spirometry) and quality of life (EQ-5D-5L). Incidence and complications of COVID-19 and/or viral infections (ie, hospitalisation, complications or death) will be recorded throughout the trial, including 3 months after supplementation is ceased. ETHICS AND DISSEMINATION: This study was approved by Melbourne Health Human Research Ethics Committee (Ref No. HREC/73985/MH-2021, ERM Ref No. RMH73985, Melbourne Health Site Ref No. 2021.115). Written informed consent will be obtained from participants. Results will be published in peer-reviewed journals and made available to key aged care stakeholders, including providers, residents, and government bodies. TRIAL REGISTRATION NUMBER: ACTRN12621000420842.

Red Yeast Rice Preparations Reduce Mortality, Major Cardiovascular Adverse Events, and Risk Factors for Metabolic Syndrome: A Systematic Review and Meta-analysis.

Background: Metabolic syndrome (MetS) is characterized by the cooccurrence of obesity, insulin resistance, dyslipidaemia, and hypertension. Red yeast rice (RYR) preparations might be beneficial for the prevention and treatment of MetS. Objective: To implement a systematic review and meta-analysis to determine whether RYR preparations improve clinical endpoints and reduce risk factors for MetS. Methods: The PubMed, Cochrane Library, EMBASE, Scopus, China National Knowledge Infrastructure, Chinese VIP Information, and WanFang databases were searched for randomized controlled trials (published up to September 2020), and a meta-analysis was performed using fixed- or random-effects models. The primary outcome measures were mortality and major adverse cardiovascular events (MACEs), and the secondary outcome measures were biochemical parameters of blood glucose, blood lipids, and blood pressure. The registration number is CRD42020209186. Results: A total of 921 articles were identified, of which 30 articles were included in this article. RYR preparations group demonstrated significant improvements in MetS compared with control group. RYR preparations reduced the mortality and MACEs (RR = 0.62, 95% CI [0.49, 0.78]; RR = 0.54, 95% CI [0.43, 0.66]). In terms of blood glucose metabolism, fasting plasma glucose (FPG) (MD = -0.46 mmol/L, 95% CI [-0.71, -0.22]), haemoglobin A1c (HbA1c) (MD = -0.49, 95% CI [-0.71, -0.26]) and the homeostasis model assessment of insulin resistance (HOMA-IR) (MD = -0.93, 95% CI [-1.64, -0.21]) were decreased. Regarding the lipid metabolism, total cholesterol (TC) (MD = -0.74 mmol/L, 95% CI [-1.02, -0.46]), triglycerides (TG) (MD = -0.45 mmol/L, 95% CI [-0.70, -0.21]), and low-density lipoprotein cholesterol (LDL) (MD = -0.42 mmol/L, 95% CI [-0.78, -0.06]) were decreased, while high-density lipoprotein cholesterol (HDL) (MD = 0.14 mmol/L, 95% CI [0.09, 0.20]) was increased. Regarding blood pressure, the mean arterial pressure (MAP) (MD = -3.79 mmHg, 95% CI [-5.01, -2.57]) was decreased. In addition, RYR preparations did not increase the incidence of adverse reactions (RR = 1.00, 95% CI [0.69, 1.43]). Conclusion: RYR preparations reduce mortality, MACEs, and multiple risk factors for MetS without compromising safety, which supports its application for the prevention and treatment of MetS. However, additional high-quality studies are needed to provide more evidence for the effect of RYR on MetS due to the heterogeneity in this study. Systematic Review Registration: www.crd.york.ac.uk/PROSPERO, identifier CRD42020209186.