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Older adults in nursing homes are at greatest risk of morbidity and mortality from SARS-CoV-2 infection. Nursing home residents constituted one-third to more than half of all deaths during the early waves of the COVID-19 pandemic. Following this, widespread adaptation of infection prevention and control measures and the supply and use of personal protective equipment resulted in a significant decrease in nursing home infections and deaths. For nursing homes, the most important determinant of experiencing a SARS-CoV-2 outbreak in the first instance appears to be community-transmission levels (particularly with variants of concern), although nursing home size and quality, for-profit status, and sociodemographic characteristics are also important. Use of visitation bans, imposed to reduce the impact of COVID-19 on residents, must be delicately balanced against their impact on resident, friend or family, and staff well-being. The successful rollout of primary vaccination has resulted in a sharp decrease in morbidity and mortality from SARS-CoV-2 in nursing homes. However, emerging evidence suggests that vaccine efficacy may wane over time, and the use of a third or additional vaccine "booster" doses in nursing home residents restores protection afforded by primary vaccination. Ongoing monitoring of vaccine efficacy in terms of infection, morbidity, and mortality is crucial in this vulnerable group in informing ongoing SARS-CoV-2 vaccine boosting strategies. Here, we detail the impact of SARS-CoV-2 on nursing home residents and discuss important considerations in the management of nursing home SARS-CoV-2 outbreaks. We additionally examine the use of testing strategies, nonpharmacologic outbreak control measures and vaccination strategies in this cohort. Finally, the impact of SARS-CoV-2 on the sector is reflected on as we emphasize the need for adoption of universal standards of medical care and integration with wider public health infrastructure in nursing homes in order to provide a safe and effective long-term care sector.

Midlife Type 2 Diabetes Mellitus (T2DM) is associated with an increased risk of Alzheimer Disease (AD) in later life, with altered inflammatory responses postulated as key pathological drivers. Previous studies have demonstrated increased responsiveness to NLR family pyrin domain containing 3 (NLRP3) inflammasome agonists, both in individuals with untreated T2DM in addition to those with established AD. We hypothesised that peripheral NLRP3 inflammasome responses may be altered during the early stages of T2DM-related cognitive dysfunction. Here, we assessed the relationship between NLPR3 responses in peripheral blood mononuclear cells (including to Aβ-42, the putative pathogenic protein in AD) and neuropsychological performance in uncomplicated midlife T2DM to identify early signatures of immune dysregulation which may predispose to later cognitive decline. We recruited a cross-sectional cohort of middle-aged adults with uncomplicated T2DM and matched Healthy Controls (HCs) for comprehensive neuropsychological assessment and in vitro PBMC responses to a range of NLRP3 agonists were assessed. T2DM was associated with subtle decrements on neuropsychological tests of delayed memory and executive function (both p

International audience; Serological assays capable of measuring antibody responses induced by previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been critical tools in the response to the COVID-19 pandemic. In this study, we use bead-based multiplex assays to measure IgG and IgA antibodies and IgG avidity to five SARS-CoV-2 antigens (Spike (S), receptor-binding domain (RBD), Nucleocapsid (N), S subunit 2, and Membrane-Envelope fusion (ME)). These assays were performed in several cohorts of healthcare workers and nursing home residents, who were followed for up to eleven months after SARS-CoV-2 infection or up to six months after vaccination. Our results show distinct kinetic patterns of antibody quantity (IgG and IgA) and avidity. While IgG and IgA antibody levels waned over time, with IgA antibody levels waning more rapidly, avidity increased with time after infection or vaccination. These contrasting kinetic patterns allow for the estimation of time since previous SARS-CoV-2 infection. Including avidity measurements in addition to antibody levels in a classification algorithm for estimating time since infection led to a substantial improvement in accuracy, from 62% to 78%. The inclusion of antibody avidity in panels of serological assays can yield valuable information for improving serosurveillance during SARS-CoV-2 epidemics.

Objectives Older nursing home residents make up the population at greatest risk of morbidity and mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. No studies have examined the determinants of long-term antibody responses post vaccination in this group. Design Longitudinal cohort study. Setting and Participants Residents from 5 nursing homes assessed before vaccination, and 5 weeks and 6 months post vaccination, with the BNT162b2 messenger RNA SARS-CoV-2 vaccine. Methods Comprehensive clinical assessment was performed, including assessment for comorbidity, frailty, and SARS-CoV-2 infection history. Serum nucleocapsid and anti-spike receptor binding domain (RBD) antibodies were analyzed at all timepoints. An in vitro angiotensin-converting enzyme (ACE2) receptor-spike RBD neutralization assay assessed serum neutralization capacity. Results Of 86 participants (81.1 ± 10.8 years; 65% female), just under half (45.4%; 39 of 86) had evidence of previous SARS-CoV-2 infection. All participants demonstrated a significant antibody response to vaccination at 5 weeks and a significant decline in this response by 6 months. SARS-CoV-2 infection history was the strongest predictor of antibody titer (log-transformed) at both 5 weeks [β: 3.00; 95% confidence interval (CI): 2.32–3.70; P < .001] and 6 months (β: 3.59; 95% CI: 2.89–4.28; P < .001). Independent of SARS-CoV-2 infection history, both age in years (β: −0.05; 95% CI: −0.08 to −0.02; P < .001) and frailty (β: −0.22; 95% CI: −0.33 to −0.11; P < .001) were associated with a significantly lower antibody titer at 6 months. Anti-spike antibody titers at both 5 weeks and 6 months significantly correlated with in vitro neutralization capacity. Conclusions and Implications In older nursing home residents, SARS-CoV-2 infection history was the strongest predictor of anti-spike antibody titers at 6 months, whereas age and frailty were independently associated with lower titers at 6 months. Antibody titers significantly correlated with in vitro neutralization capacity. Although older SARS-CoV-2 naïve nursing home residents may be particularly vulnerable to breakthrough SARS-CoV-2 infection, the relationship between antibody titers, SARS-CoV-2 infection, and clinical outcomes remains to be fully elucidated in this vulnerable population.

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4%80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals70 years, 2.3% between 70 and 80 years, and 6.3%80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.

Contains fulltext : 218263.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Benzodiazepines and related drugs (BDZRs) have been associated with an increased risk of Alzheimer's disease (AD) in later life. Despite this, it remains unclear whether ongoing BDZR use may further accelerate cognitive decline in those diagnosed with mild to moderate AD. DESIGN: This study was embedded within NILVAD, a randomized controlled trial of nilvadipine in mild to moderate AD. Cognition was measured at baseline and 18 months using the Alzheimer Disease Assessment Scale, Cognitive Subsection (ADAS-Cog). We assessed predictors of long-term BDZR use and analyzed the effect of ongoing BDZR use on ADAS-Cog scores at 18 months. Additionally, the impact of BDZR use on adverse events, incident delirium, and falls over 18-month follow-up was assessed adjusting for relevant covariates. SETTING AND PARTICIPANTS: 448 participants with mild to moderate AD recruited from 23 academic centers in 9 European countries. RESULTS: Overall, 14% (62/448) were prescribed an ongoing BDZR for the study duration. Increasing total number of (non-BDZR) medications was associated with a greater likelihood of BDZR prescription (odds ratio 1.16, 95% confidence interval 1.05-1.29). At 18 months, BDZR use was not associated with greater cognitive decline on the ADAS-Cog controlling for baseline ADAS-Cog scores, age, gender, study arm, and other clinical covariates (beta = 1.62, -1.34 to 4.56). However, ongoing BDZR use was associated with a greater likelihood of adverse events [incidence rate ratio (IRR) 1.19, 1.05-1.34], incident delirium (IRR 2.31, 1.45-3.68), and falls (IRR 1.66, 1.02-2.65) over 18 months that persisted after robust adjustment for covariates. CONCLUSIONS AND IMPLICATIONS: This study found no effect of ongoing BDZR use on ADAS-Cog scores in those with mild to moderate AD over 18 months. However, ongoing use of these medications was associated with an increased risk of adverse events, delirium, and falls. Thus, BDZR use should be avoided where possible and deprescribing interventions should be encouraged in older adults with AD.