scholarly journals Neutralising antibody activity against SARS-CoV-2 variants, including Omicron, in an elderly cohort vaccinated with BNT162b2

2021 ◽  
Author(s):  
Joseph Newman ◽  
Nazia Thakur ◽  
Thomas P Peacock ◽  
Dagmara Bialy ◽  
Ahmed ME Elreafey ◽  
...  
Keyword(s):  
The Elderly ◽  
Antibody Activity ◽  
Receptor Binding Domain ◽  
Specific Receptor ◽  
Neutralising Antibodies ◽  
Important Data ◽  
Ongoing Surveillance ◽  
Elderly Cohort ◽  
Over Time ◽  
Time Point

SARS-CoV-2 variants threaten the effectiveness of tools we have developed to mitigate against serious COVID-19. This is especially true in clinically vulnerable sections of society including the elderly. Using sera from BNT162b2 (Pfizer-BioNTech) vaccinated individuals aged between 70 and 89 (vaccinated with two doses 3-weeks apart) we examined the neutralising antibody (nAb) response to wildtype SARS-CoV-2. Between 3 and 20-weeks post 2nd dose, nAb titres dropped 4.9-fold to a median titre of 21.3 (ND80) with 21.6% of individuals having no detectable nAbs at the later time point. Experiments examining the neutralisation of twenty-one different SARS-CoV-2 variant spike proteins confirmed a significant potential for antigenic escape, especially for the Omicron (BA.1), Beta (B.1.351), Delta (B.1.617.2), Theta (P.3), C.1.2 and B.1.638 variants. Interestingly, however, the recently-emerged sub-lineage AY.4.2 was more efficiently neutralised than parental Delta pseudotypes. Combining pseudotype neutralisation with specific receptor binding domain (RBD) ELISAs we confirmed that changes to position 484 in the spike RBD were predominantly responsible for SARS-CoV-2 nAb escape, although the effect of spike mutations is both combinatorial and additive. Lastly, using sera from the same individuals boosted with a 3rd dose of BNT162b2 we showed that high overall levels of neutralising antibody titre can provide significant levels of cross-protection against Omicron. These data provide evidence that SARS-CoV-2 neutralising antibodies wane over time and that antigenically variable SARS-CoV-2 variants are circulating, highlighting the importance of ongoing surveillance and booster programmes. Furthermore, they provide important data to inform risk assessment of new SARS-CoV-2 variants, such as Omicron, as they emerge.

scholarly journals Levels of physical activity in four domains and affective wellbeing before and during the Covid-19 pandemic

2021 ◽  
Vol 79 (1) ◽  
Author(s):  
Eliane S. Engels ◽  
Michael Mutz ◽  
Yolanda Demetriou ◽  
Anne K. Reimers
Keyword(s):  
Mental Health ◽  
Physical Activity ◽  
Protective Factor ◽  
Total Sample ◽  
Poor Mental Health ◽  
German Population ◽  
Time Points ◽  
Sport And Exercise ◽  
Over Time ◽  
Time Point

Abstract Background Latest studies indicated that the general mental health level is low during the pandemic. Probably, this deterioration of the mental health situation is partly due to declines in physical activity. The aim of this study was to investigate differences in and the association between affective wellbeing and levels of different domains of physical activity at three time points before and during the pandemic. Method We used a nationwide online panel with a trend data design encompassing a total sample of N = 3517, representing the German population (> 14 years). Four different activity domains (sport and exercise, light outdoor activity, housework/gardening, active travel) and affective wellbeing (positive and negative affect) were assessed at three time points before and during the Covid-19 pandemic (October 2019, March 2020, October 2020). Results Multivariate analyses of variance (MANOVA) indicate differences regarding affective wellbeing over the three time points with the lowest values at the second time point. Levels of activity in the four domains differed significantly over time with the strongest decrease for sport and exercise from the first to the second time point. Partial correlations indicated that the relationships between sport and exercise and positive affect were most consistent over time. Conclusions Overall, our findings suggest that physical activity plays a particularly important role in the pandemic period as a protective factor against poor mental health. Especially sports and exercise seem to be supportive and should be encouraged, e.g. by providing additional support in finding adequate outdoor, home-based or digital substitutes.

scholarly journals 10. Kinetics of Post-Vaccination Seroprotection to S. Pneumonia for the Immune-Compromised and Vaccine-Naïve Populations

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S27-S28
Author(s):  
Jeffrey Gruenglas ◽  
James Mond ◽  
Micaela Scobie ◽  
Cynthia Tolman ◽  
Joseph Martinez
Keyword(s):  
Capsular Polysaccharide ◽  
The Elderly ◽  
Community Acquired Pneumonia ◽  
Prior History ◽  
Antibody Activity ◽  
Vaccine Response ◽  
Serum Samples ◽  
Opsonic Activity ◽  
And Control

Abstract Background S. pneumonia infection presents a significant challenge, accounting for 20–38% of hospital-acquired pneumonia, and the leading cause of community-acquired pneumonia despite availability of effective vaccines. Incidence is highest in children under 2 years, the immunocompromised, and elderly. CDC has reported the emergence of antibiotic resistance in ~30% of cases, adding to risk of morbidity and mortality. Fewer than half of the elderly are vaccinated and vulnerable to infection on admission. Passive immunotherapy as an adjunct to vaccines may improve outcomes in such populations. The objective of this study was to evaluate whether seroprotective response induced with a pneumococcal conjugate vaccine could rapidly yield protective opsonic levels of antibody within anticipated duration of hospitalization. Methods Healthy donors (n=30) were immunized with Prevnar. Blood was drawn on days 0, 3, 7, 10, 14, 21, and 28. Samples were pooled and tested for presence of functional opsonic antibodies recognizing capsular polysaccharides. Clearance mechanism of S. pneumonia was based on antibody recognition to pneumococcal capsular polysaccharide and opsonic titers used as an in vitro surrogate to evaluate the efficacy of vaccine. Results There was little to no opsonic activity against most serotypes on day 0, except for low antibody activity with serotypes 1, 3, 4, and 5. Titers increased, with protective levels achieved by day 10 for most serotypes (except 14 and 18C), peaking at day 14 or after across serotypes (Figures 1 and 2). Average titers rose from log2 titer 2 on day 0 to log2 titer 8 on days 21 and 28. Titers against most serotypes reached log2 10 (titer 1024) or higher. Patients remained susceptible to nosocomial infection for at least 10 days post admission until protective titers are reached. OPK titers (log2 scale) for serum samples on day 0 (pre), day 3, 7, 10, 14, 21, 28, and control for S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V. N=2. OPK titers (log2 scale) for serum samples on day 0 (pre), day 3, 7, 10, 14, 21, 28, and control for S. pneumoniae serotypes 14, 18C, 19A, 19F, and 23F. N=2. Conclusion Patients with no prior history of vaccination (or inability to mount response) with Prevnar or pneumovax remain vulnerable to S. pneumonia infection even if vaccinated on entry, due to delayed kinetics in reaching protective titers. These patients may require prophylactic intervention of hyperimmune Ig with high opsonic titers to S. pneumonia, providing protection until vaccine response elicits protective antibodies. Disclosures All Authors: No reported disclosures

scholarly journals Design of a companion bioinformatic tool to detect the emergence and geographical distribution of SARS-CoV-2 Spike protein genetic variants

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Alice Massacci ◽  
Eleonora Sperandio ◽  
Lorenzo D’Ambrosio ◽  
Mariano Maffei ◽  
Fabio Palombo ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Consensus Sequence ◽  
Cell Epitope ◽  
Vaccine Design ◽  
Binding Domain ◽  
Spike Protein ◽  
Antibody Activity ◽  
Binding Motif ◽  
Receptor Binding Domain ◽  
The Impact

Abstract Background Tracking the genetic variability of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) is a crucial challenge. Mainly to identify target sequences in order to generate robust vaccines and neutralizing monoclonal antibodies, but also to track viral genetic temporal and geographic evolution and to mine for variants associated with reduced or increased disease severity. Several online tools and bioinformatic phylogenetic analyses have been released, but the main interest lies in the Spike protein, which is the pivotal element of current vaccine design, and in the Receptor Binding Domain, that accounts for most of the neutralizing the antibody activity. Methods Here, we present an open-source bioinformatic protocol, and a web portal focused on SARS-CoV-2 single mutations and minimal consensus sequence building as a companion vaccine design tool. Furthermore, we provide immunogenomic analyses to understand the impact of the most frequent RBD variations. Results Results on the whole GISAID sequence dataset at the time of the writing (October 2020) reveals an emerging mutation, S477N, located on the central part of the Spike protein Receptor Binding Domain, the Receptor Binding Motif. Immunogenomic analyses revealed some variation in mutated epitope MHC compatibility, T-cell recognition, and B-cell epitope probability for most frequent human HLAs. Conclusions This work provides a framework able to track down SARS-CoV-2 genomic variability.

scholarly journals Knee Muscle Strength Recovery in the Early Period After ACL Reconstruction

2014 ◽  
Vol 2 (11_suppl3) ◽  
pp. 2325967114S0014
Author(s):  
Gulcan Harput ◽  
Hasan Erkan Kılınc ◽  
Hamza Özer ◽  
Gül Baltacı ◽  
Carl G. Mattacola
Keyword(s):  
Acl Reconstruction ◽  
Early Period ◽  
Quadriceps Strength ◽  
Isometric Strength ◽  
Time Points ◽  
Hamstring Muscles ◽  
Significant Difference ◽  
Isometric Torque ◽  
Over Time ◽  
Time Point

Objectives: The aim of this study was to investigate quadriceps and hamstrings isometric strength at 4, 8 and 12 week time points following ACL Reconstruction (ACLR) and to document the strength changes of these muscles over time. The primary hypothesis was that there would be significant increases in quadriceps and hamstring muscle strengths between the 4th, 8th and 12th weeks following ACLR. The secondary hypothesis was that the quadriceps index would be higher than hamstring index at 12th week after ACLR. Methods: Thirty patients (Mean ± SD [age, 29.1±2.3yrs; weight, 77.3±13.2kg; height, 172.1±7.1cm; BMI, 21.2±3.5kg/m2, time to surgery: 7.1±7.2 months]) who underwent ACLR with Hamstring Tendon Autograft (HTG) were enrolled in this study. The isometric strength of quadriceps and hamstring muscles was measured on an isokinetic dynamometer at 60° knee flexion angle at 4th, 8th and 12th weeks after surgery. The recovery of quadriceps and hamstring muscles strength following rehabilitation was expressed as a Quadriceps Index (QI) and Hamstring Index (HI) and calculated with the following formula:[(maximum voluntary isometric torque of the involved limb / maximum voluntary isometric torque by uninvolved limb) × 100]. Torque output of the involved and uninvolved limbs and quadriceps and hamstring indexes were used for the statistical analysis. A repeated measures of ANOVA was used to determine the strength changes of quadriceps and hamstrings over time. Results: Quadriceps and Hamstrings strengths significantly increased over time for both involved (Quadriceps: F (2,46)=58.3, p<0.001, Hamstring: F (2,46)=35.7, p<0.001) and uninvolved limb (Quadriceps: F(2,46)=17.9, p<0.001, Hamstring: F(2,46)=56.9, p=0.001 ). Quadriceps strength was higher at 12th week when compared to the 8 and 4 week time points for the involved limb (p<0.001), and it was higher at 8th week when compared to 4 week time point for the involved limb (p<0.001). For the uninvolved limb, quadriceps strength was also higher at 12th week when compared to the 8 (p=0.02) and 4 week time point (p<0.001), and higher at 8 week when compared to the 4 week time point (p=0.02). Hamstring strength was higher at 12 week when compared to the 8 and 4 week time points (p<0.001) and it was higher at 8 week when compared to 4 week time point for the involved limb (p<0.001). For the uninvolved limb hamstring strength was also higher at 12 week when compared to 4 week time point (p=0.01). There was no significant difference between the 4 and 8 week time points (p>0.05) or between the 8 and 12 week time points (p=0.07). Quadriceps and hamstring indexes significantly changed from 4th weeks (QI:57.9, HI:54.4 ) to 8th weeks (QI:78.8, HI:69.9 ) and from 8th weeks to 12th weeks (QI:82, HI:75.7 ) (p<0.001); however, there was no difference between indexes at the 12-week time point (p=0.17). Conclusion: Isometric strength of quadriceps and hamstring muscles for the involved and uninvolved limb increased during the early period of ACLR. The results of this study could be a baseline for clinicians while prescribing a rehabilitation protocol for ACLR patients with HTG to better appreciate expected strength changes of the muscles in the early phase.

Cochlear implantation in elderly patients: stability of outcome over time

2016 ◽  
Vol 130 (8) ◽  
pp. 706-711 ◽  
Author(s):  
O Hilly ◽  
E Hwang ◽  
L Smith ◽  
D Shipp ◽  
J M Nedzelski ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Cochlear Implantation ◽  
Short Form ◽  
Age Groups ◽  
The Elderly ◽  
Long Term Results ◽  
Profound Hearing Loss ◽  
Younger Patients ◽  
Over Time

AbstractBackground:Cochlear implantation is the standard of care for treating severe to profound hearing loss in all age groups. There is limited data on long-term results in elderly implantees and the effect of ageing on outcomes. This study compared the stability of cochlear implantation outcome in elderly and younger patients.Methods:A retrospective chart review of cochlear implant patients with a minimum follow up of five years was conducted.Results:The study included 87 patients with a mean follow up of 6.8 years. Of these, 22 patients were older than 70 years at the time of implantation. Hearing in Noise Test scores at one year after implantation were worse in the elderly: 85.3 (aged under 61 years), 80.5 (61–70 years) and 73.6 (aged over 70 years;p= 0.039). The respective scores at the last follow up were 84.8, 85.1 and 76.5 (p= 0.054). Most patients had a stable outcome during follow up. Of the elderly patients, 13.6 per cent improved and none had a reduction in score of more than 20 per cent. Similar to younger patients, elderly patients had improved Short Form 36 Health Survey scores during follow up.Conclusion:Cochlear implantation improves both audiometric outcome and quality of life in elderly patients. These benefits are stable over time.

An End to Incrementalism? The Impact of Expenditure Restraint on Social Services Budgets 1979–1986

1989 ◽  
Vol 18 (2) ◽  
pp. 187-210 ◽  
Author(s):  
Aidan Kelly
Keyword(s):  
Social Services ◽  
Social Service ◽  
The Elderly ◽  
Activity Data ◽  
The Public ◽  
Total Budget ◽  
Service Departments ◽  
The Impact ◽  
The Relationship ◽  
Over Time

ABSTRACTThe theory of incrementalism is a long-standing and influential perspective on policy making and resource allocation in the public sector. Previous research on social services budgeting suggests that resources are allocated incrementally, although there has been some debate as to whether this would persist in an era of prolonged expenditure restraint. Incremental budgetary outcomes are operationalised as percentage changes in budgets pro-rata with percentage changes in the total budget, and as stable shares of total expenditure for each activity. Data for 99 English social service departments supports incrementalism in that budget shares change by only 1.8 per cent, but percentage allocations depart from pro-rata incrementalism by a mean of 74 per cent. The comparison of the two summary indices over time supports those who have argued that prolonged restraint would encourage non-incremental budgeting, but change in the agency's total budget does not consistently predict budgetary outcomes. The effect of restraint on incrementalism varies with the measure used and across the component activities of the measures, but there is enough evidence to suggest a significant decline in the level of incrementalism in social service departments. In particular, non-incremental budgeting is strongly associated with the growth of day centre expenditure on the mentally ill and the elderly before 1982–3, and after that with the pursuit of the ‘community care’ strategy within state provided services for the elderly and children. Incrementalism as a general theory of agency budgeting is limited in its ability to explain variations in the degree of incrementalism between agencies, between component budgets and over time. The conclusion suggests that further research should seek explanations for these variations in the varying balance of the competing forces which shape outcomes in welfare bureaucracies and in the relationship between these forces and the organisation's environment.

scholarly journals Nitrogenous metabolism in Thoroughbred and Arabian foals from birth to five months of age

2006 ◽  
Vol 58 (4) ◽  
pp. 525-529 ◽  
Author(s):  
G. Piccione ◽  
A. Costa ◽  
F. Fazio ◽  
F. Grasso ◽  
G. Caola
Keyword(s):  
Uric Acid ◽  
Serum Concentration ◽  
Nitrogen Metabolism ◽  
Rectal Temperature ◽  
Total Protein ◽  
Critical Period ◽  
Critical Period Of Development ◽  
Over Time ◽  
Time Point ◽  
Nitrogenous Metabolism

The maturation of nitrogen metabolism was studied in six Thoroughbred and six Arabian foals. Rectal temperature, heart and respiratory rates and serum concentration of several hematochemical parameters (total protein, urea, uric acid, creatinine, and albumine) were monitored from birth to 5 months of age. In both breeds, all the parameters except albumine showed significant differences over time (P<0.05). The two breeds did not differ from each other at any time point. Statistically significant decreases in urea and creatinine concentrations were related to the growth needs of foals during this critical period of development.

scholarly journals SARS-CoV-2 B.1.617 emergence and sensitivity to vaccine-elicited antibodies

2021 ◽  
Author(s):  
Isabella Ferreira ◽  
Rawlings Datir ◽  
Guido Papa ◽  
Steven Kemp ◽  
Bo Meng ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Growth Rates ◽  
Cleavage Site ◽  
Syncytium Formation ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Additive Effects ◽  
Neutralising Antibodies ◽  
Indian State

The B.1.617 variant emerged in the Indian state of Maharashtra in late 2020 and has spread throughout India and to at least 40 countries. There have been fears that two key mutations seen in the receptor binding domain L452R and E484Q would have additive effects on evasion of neutralising antibodies. Here we delineate the phylogenetics of B.1.617 and spike mutation frequencies, in the context of others bearing L452R. The defining mutations in B.1.617.1 spike are L452R and E484Q in the RBD that interacts with ACE2 and is the target of neutralising antibodies. All B.1.617 viruses have the P681R mutation in the polybasic cleavage site region in spike. We report that B.1.617.1 spike bearing L452R, E484Q and P681R mediates entry into cells with slightly reduced efficiency compared to Wuhan-1. This spike confers modestly reduced sensitivity to BNT162b2 mRNA vaccine-elicited antibodies that is similar in magnitude to the loss of sensitivity conferred by L452R or E484Q alone. Furthermore we show that the P681R mutation significantly augments syncytium formation upon the B.1.617.1 spike protein, potentially contributing to increased pathogenesis observed in hamsters and infection growth rates observed in humans.

Delirium superimposed on dementia: defining disease states and course from longitudinal measurements of a multivariate index using latent class analysis and hidden Markov chains

2011 ◽  
Vol 23 (10) ◽  
pp. 1659-1670 ◽  
Author(s):  
Antonio Ciampi ◽  
Alina Dyachenko ◽  
Martin Cole ◽  
Jane McCusker
Keyword(s):  
Mental Disorders ◽  
Markov Chains ◽  
Latent Class Analysis ◽  
Latent Class ◽  
Hidden Markov ◽  
The Elderly ◽  
Population Heterogeneity ◽  
Class Analysis ◽  
Hidden Markov Chains ◽  
Time Point

ABSTRACTBackground: The study of mental disorders in the elderly presents substantial challenges due to population heterogeneity, coexistence of different mental disorders, and diagnostic uncertainty. While reliable tools have been developed to collect relevant data, new approaches to study design and analysis are needed. We focus on a new analytic approach.Methods: Our framework is based on latent class analysis and hidden Markov chains. From repeated measurements of a multivariate disease index, we extract the notion of underlying state of a patient at a time point. The course of the disorder is then a sequence of transitions among states. States and transitions are not observable; however, the probability of being in a state at a time point, and the transition probabilities from one state to another over time can be estimated.Results: Data from 444 patients with and without diagnosis of delirium and dementia were available from a previous study. The Delirium Index was measured at diagnosis, and at 2 and 6 months from diagnosis. Four latent classes were identified: fairly healthy, moderately ill, clearly sick, and very sick. Dementia and delirium could not be separated on the basis of these data alone. Indeed, as the probability of delirium increased, so did the probability of decline of mental functions. Eight most probable courses were identified, including good and poor stable courses, and courses exhibiting various patterns of improvement.Conclusion: Latent class analysis and hidden Markov chains offer a promising tool for studying mental disorders in the elderly. Its use may show its full potential as new data become available.

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