Do quantitative levels of antispike-IgG antibodies aid in predicting protection from SARS-CoV-2 infection? Results from a longitudinal study in a police cohort.

In a COVID-19 sero-surveillance cohort study with predominantly healthy and vaccinated individuals, the objectives were (i) to investigate longitudinally the factors associated with the quantitative dynamics of antispike (anti-S1) IgG antibody levels, (ii) to evaluate whether the levels were associated with protection from SARS-CoV-2 infection, and (iii) to assess whether the association was different in the pre-Omicron compared with the Omicron period. The QuantiVac Euroimmun ELISA test was used to quantify anti-S1 IgG levels. The entire study period (16 months), the 11-month pre-Omicron period and the cross-sectional analysis before the Omicron surge included 3219, 2310, and 895 reactive serum samples from 949, 919, and 895 individuals, respectively. Mixed-effect linear, mixed-effect time-to-event, and logistic regression models were used to achieve the objectives. Age and time since infection or vaccination were the only factors associated with a decline of anti-S1 IgG levels. Higher antibody levels were significantly associated with protection from SARS-CoV-2 infection (0.89, 95% confidence interval [CI] 0.82-0.97), and the association was higher during the time period when Omicron was predominantly circulating compared with the ones when Alpha and Delta variants were predominant (adjusted hazard ratio for interaction 0.66, 95% CI 0.53-0.84). In a prediction model, it was estimated that >8000 BAU/mL anti-S1 IgG was required to reduce the risk of infection with Omicron variants by approximately 20%-30% for 90 days. Though, such high levels were only found in 1.9% of the samples before the Omicron surge, and they were not durable for 3 months. Anti-S1 IgG antibody levels are statistically associated with protection from SARS-CoV-2 infection. However, the prediction impact of the antibody level findings on infection protection is limited.

Recovering Hidden Responder Groups in Individuals Receiving Neurofeedback for Tinnitus.

The widespread understanding that chronic tinnitus is a heterogeneous phenomenon with various neural oscillatory profiles has spurred investigations into individualized approaches in its treatment. Neurofeedback, as a non-invasive tool for altering neural activity, has become increasingly popular in the personalized treatment of a wide range of neuropsychological disorders. Despite the success of neurofeedback on the group level, the variability in the treatment efficacy on the individual level is high, and evidence from recent studies shows that only a small number of people can effectively modulate the desired aspects of neural activity. To reveal who may be more suitable, and hence benefit most from neurofeedback treatment, we classified individuals into unobserved subgroups with similar oscillatory trajectories during the treatment and investigated how subgroup membership was predicted by a series of characteristics. Growth mixture modeling was used to identify distinct latent subgroups with similar oscillatory trajectories among 50 individuals suffering from chronic subjective tinnitus (38 male, 12 female, mean age = 47.1 ± 12.84) across 15 neurofeedback training sessions. Further, the impact of characteristics and how they predicted the affiliation in the identified subgroups was evaluated by including measures of demographics, tinnitus-specific (Tinnitus Handicap Inventory) and depression variables, as well as subjective quality of life subscales (World Health Organization-Quality of Life Questionnaire), and health-related quality of life subscales (Short Form-36) in a logistic regression analysis. A latent class model could be fitted to the longitudinal data with a high probability of correctly classifying distinct oscillatory patterns into 3 different groups: non-responder (80%), responder (16%), and decliner (4%). Further, our results show that the health-related wellbeing subscale of the Short Form-36 questionnaire was differentially associated with the groups. However, due to the small sample size in the Responder group, we are not able to provide sufficient evidence for a distinct responder profile. Nevertheless, the identification of oscillatory change-rate differences across distinct groups of individuals provides the groundwork from which to tease apart the complex and heterogeneous oscillatory processes underlying tinnitus and the attempts to modify these through neurofeedback. While more research is needed, our results and the analytical approach presented may bring clarity to contradictory past findings in the field of tinnitus research, and eventually influence clinical practice.

Serosurveillance after a COVID-19 vaccine campaign in a Swiss police cohort.

INTRODUCTION: To assess the risk for COVID-19 of police officers, we are studying the seroprevalence in a cohort. The baseline cross-sectional investigation was performed before a vaccination campaign in January/February 2021, and demonstrated a seroprevalence of 12.9%. Here, we demonstrate serosurveillance results after a vaccination campaign. METHODS: The cohort consists of 1022 study participants. The 3- and 6-month follow-up visits were performed in April/May and September 2021. Data on infection and vaccination rates were obtained via measuring antibodies to the nucleocapsid protein and spike protein and online questionnaires. RESULTS: The mean age of the population was 41 (SD 8.8) years, 72% were male and 76% had no comorbidity. Seroconversion was identified in 1.05% of the study population at the 3-month visit and in 0.73% at the 6-month visit, resulting in an infection rate of 1.8% over a time period of 6 months. In comparison, the infection rate in the general population over the same time period was higher (3.18%, p = .018). At the 6-month visit, 77.8% of participants reported being vaccinated once and 70.5% twice; 81% had an anti-S antibody titer of >250 U/ml and 87.1% of ≥2 U/ml. No significant association between infection and job role within the department, working region, or years of experience in the job was found. Anti-spike antibody titers of vaccinated study participants showed a calculated decreasing trend 150-200 days after the second vaccine dose. CONCLUSION: These data confirm the value of the vaccination campaign in an exposed group other than healthcare professionals.

A Multidimensional Cross-Sectional Analysis of Coronavirus Disease 2019 Seroprevalence Among a Police Officer Cohort: The PoliCOV-19 Study.

BACKGROUND: Protests and police fieldwork provide a high-exposure environment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. In this cross-sectional analysis, we investigated the seroprevalence among a police cohort, and sociodemographic, work, and health-related factors associated with seropositivity. METHODS: Study participants were invited for serological testing of SARS-CoV-2 and to complete online questionnaires. Serum neutralization titers toward the wild-type SARS-CoV-2 spike protein (expressing D614G) and the Alpha and Beta variants were measured in seropositive study participants. RESULTS: A total of 978 police personnel representing 35% of the entire staff participated from February to March 2021. The seroprevalence was 12.9%. It varied by geographic region, ranged from 9% to 13.5% in 3 regions, including the city; and was 22% in Bernese Seeland/Jura with higher odds for seropositivity (odds ratio [OR], 2.38 [95% confidence interval {CI}, 1.28-4.44], P=.006). Job roles with mainly office activity were associated with a lower risk of seropositivity (OR, 0.33 [95% CI, .14-.77], P=.010). Self-reported compliance with mask wearing during working hours was 100%; 45% of seropositive vs 5% of seronegative participants (P<.001) reported having had contact with a proven coronavirus disease 2019 (COVID-19) case living in the same household prior to serological testing. The level of serum antibody titers correlated with neutralization capacity. Antibodies derived from natural SARS-CoV-2 infection effectively neutralized the SARS-CoV-2 spike protein, but were less effective against the Alpha and Beta variants. CONCLUSIONS: The seroprevalence of anti-SARS-CoV-2 antibodies of police officers was comparable to that reported in the general population, suggesting that the personal protective equipment of the police is effective, and that household contacts are the leading transmission venues. The level of serum antibody titers, in particular that of anti-spike antibodies, correlated well with neutralization capacity. Low antibody titers acquired from natural infection were not effective against variants. CLINICAL TRIALS REGISTRATION: NCT04643444.

Application of Latent Growth Curve modeling to predict individual trajectories during neurofeedback treatment for tinnitus.

Tinnitus is a heterogeneous phenomenon indexed by various EEG oscillatory profiles. Applying neurofeedback (NFB) with the aim of changing these oscillatory patterns not only provides help for those who suffer from the phantom percept, but a promising foundation from which to probe influential factors. The reliable attribution of influential factors that potentially predict oscillatory changes during the course of NFB training may lead to the identification of subgroups of individuals that are more or less responsive to NFB training. The present study investigated oscillatory trajectories of delta (3-4Hz) and individual alpha (8.5-12Hz) during 15 NFB training sessions, based on a Latent Growth Curve framework. First, we found the desired enhancement of alpha, while delta was stable throughout the NFB training. Individual differences in tinnitus-specific variables and general-, as well as health-related quality of life predictors were largely unrelated to oscillatory change prior to and across the training. Only the predictors age and sex at baseline were clearly related to slow-wave delta, particularly so for older female individuals who showed higher delta power values from the start. Second, we confirmed a hierarchical cross-frequency association between the two frequency bands; however, in opposing directions to those anticipated in tinnitus. The establishment of individually tailored NFB protocols would boost this therapy's effectiveness in the treatment of tinnitus. In our analysis, we propose a conceptual groundwork toward this goal of developing more targeted treatment.

Combining neurofeedback with source estimation: Evaluation of an sLORETA neurofeedback protocol for chronic tinnitus treatment.

BACKGROUND: Alpha/delta neurofeedback has been shown to be a potential treatment option for chronic subjective tinnitus. Traditional neurofeedback approaches working with a handful of surface electrodes have been criticized, however, due to their low spatial specificity. OBJECTIVE: The purpose of this study was to evaluate an innovative tomographic neurofeedback protocol that combines neural activity measured across the whole scalp with sLORETA source estimation. METHODS: Forty-eight tinnitus patients participated in 15 neurofeedback training sessions as well as extensive pre, post, and follow-up testing. Patients were randomly assigned to either a tomographic (TONF) or a traditional electrode-based neurofeedback (NTNF) group. Main outcome measures of this study were defined as tinnitus-related distress measured with the Tinnitus Handicap Inventory (THI) and Tinnitus Questionnaire (TQ), tinnitus loudness, and resting-state EEG activity in trained frequency bands. RESULTS: For both groups a significant reduction of tinnitus-related distress and tinnitus loudness was found. While distress changes remained persistent irrespective of group, loudness levels returned to baseline in the follow-up period. No significant between-group differences between the 2 neurofeedback applications (TONF vs. NTNF) were found, which suggests a similar contribution to symptom improvement. The trained alpha/delta ratio increased significantly over the course of the training and remained stable in the follow-up period. This effect was found irrespective of group on both surface and source levels with no meaningful differences between the 2 groups. CONCLUSIONS: Our study shows that a tomographic alpha/delta protocol should be considered a promising addition to tinnitus treatment but that more individually specific neurofeedback protocols should be developed.

Accounting for Heterogeneity: Mixed-Effects Models in Resting-State EEG Data in a Sample of Tinnitus Sufferers.

In neuroscience, neural oscillations and other features of brain activity recorded by electroencephalography (EEG) are typically statistically assessed on the basis of the study's population mean to identify possible blueprints for healthy subjects, or subjects with diagnosable neurological or psychiatric disorders. Despite some inter-individual similarities, there is reason to believe that a discernible portion of the individual brain activity is subject-specific. In order to encompass the potential individual source of variance in EEG data and psychometric parameters, we introduce an innovative application of linear mixed-effects models (LMM) as an alternative procedure for the analysis of resting-state EEG data. Using LMM, individual differences can be modelled through the assumptions of idiosyncrasy of all responses and dependency among data points (e.g., from the same subject within and across units of time) via random effects parameters. This report provides an example of how LMM can be used for the statistical analysis of resting-state EEG data in a heterogeneous group of subjects; namely, people who suffer from tinnitus (ringing in the ear/s). Results from 49 participants (38 male, mean age of 46.69 ± 12.65 years) revealed that EEG signals were not only associated with specific recording sites, but exhibited regional specific oscillations in conjunction to symptom severity. Tinnitus distress targeted the frequency bands beta3 (23.5-35 Hz) and gamma (35.5-45 Hz) in right frontal regions, whereas delta (0.5-4 Hz) exhibited significant changes in temporal-parietal sources. Further, 57.8% of the total variance in EEG power was subject-specific and acknowledged by the LMM framework and its prediction. Thus, a deeper understanding of both the underlying statistical and physiological patterns of EEG data was gained.

Investigating the Efficacy of an Individualized Alpha/Delta Neurofeedback Protocol in the Treatment of Chronic Tinnitus.

First attempts have demonstrated that the application of alpha/delta neurofeedback in the treatment of chronic tinnitus leads to a reduction of symptoms at the group level. However, recent research also suggests that chronic tinnitus is a decidedly heterogeneous phenomenon, one that requires treatment of distinct subgroups or even on an individual level. Thus, the purpose of this study was to evaluate an individually adjusted alpha/delta neurofeedback protocol. Following previous studies, the delta band fixed between 3 and 4 Hz was chosen as the frequency for inhibition. However, unlike the previous studies, the frequency range for the rewarded alpha band was not fixed between 8 and 12 Hz but rather individually determined according to each patient's specific alpha peak frequency (IAF). Twenty-six chronic tinnitus patients participated in 15 weekly neurofeedback training sessions and extensive pre- and post-tests, as well as follow-up testing 3 and 6 months after training. The main outcome measures were tinnitus-related distress measured with the Tinnitus Handicap Inventory (THI) and Tinnitus Questionnaire (TQ), tinnitus loudness, and pre- and post-training resting-state EEG activity in trained frequency bands. In Results, the neurofeedback protocol led to a significant reduction of tinnitus-related distress and tinnitus loudness. While distress remained on a low level even 6 months after the completion of training, loudness returned to baseline levels in the follow-up period. In addition, resting-state EEG activity showed an increase in the trained alpha/delta ratio over the course of the training. This ratio increase was related to training-induced changes of tinnitus-related distress as measured with TQ, mainly due to increases in the alpha frequency range. In sum, this study confirms the alpha/delta neurofeedback as a suitable option for the treatment of chronic tinnitus and represents a first step towards the development of individual neurofeedback protocols. This clinical trial was registered online at ClinicalTrials.gov (NCT02383147) and kofam.ch (SNCTP000001313).

Neurofeedback for Tinnitus Treatment - Review and Current Concepts.

An effective treatment to completely alleviate chronic tinnitus symptoms has not yet been discovered. However, recent developments suggest that neurofeedback (NFB), a method already popular in the treatment of other psychological and neurological disorders, may provide a suitable alternative. NFB is a non-invasive method generally based on electrophysiological recordings and visualizing of certain aspects of brain activity as positive or negative feedback that enables patients to voluntarily control their brain activity and thus triggers them to unlearn typical neural activity patterns related to tinnitus. The purpose of this review is to summarize and discuss previous findings of neurofeedback treatment studies in the field of chronic tinnitus. In doing so, also an overview about the underlying theories of tinnitus emergence is presented and results of resting-state EEG and MEG studies summarized and critically discussed. To date, neurofeedback as well as electrophysiological tinnitus studies lack general guidelines that are crucial to produce more comparable and consistent results. Even though neurofeedback has already shown promising results for chronic tinnitus treatment, further research is needed in order to develop more sophisticated protocols that are able to tackle the individual needs of tinnitus patients more specifically.