Estimating the share of SARS-CoV-2-immunologically naïve individuals in Germany up to June 2022.

After the winter of 2021/2022, the coronavirus disease 2019 (COVID-19) pandemic had reached a phase where a considerable number of people in Germany have been either infected with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, vaccinated or both, the full extent of which was difficult to estimate, however, because infection counts suffer from under-reporting, and the overlap between the vaccinated and recovered subpopulations is unknown. Yet, reliable estimates regarding population-wide susceptibility were of considerable interest: Since both previous infection and vaccination reduce the risk of severe disease, a low share of immunologically naïve individuals lowers the probability of further severe outbreaks, given that emerging variants do not escape the acquired susceptibility reduction. Here, we estimate the share of immunologically naïve individuals by age group for each of the sixteen German federal states by integrating an infectious-disease model based on weekly incidences of SARS-CoV-2 infections in the national surveillance system and vaccine uptake, as well as assumptions regarding under-ascertainment. We estimate a median share of 5.6% of individuals in the German population have neither been in contact with vaccine nor any variant up to 31 May 2022 (quartile range [2.5%-8.5%]). For the adult population at higher risk of severe disease, this figure is reduced to 3.8% [1.6%-5.9%] for ages 18-59 and 2.1% [1.0%-3.4%] for ages 60 and above. However, estimates vary between German states mostly due to heterogeneous vaccine uptake. Excluding Omicron infections from the analysis, 16.3% [14.1%-17.9%] of the population in Germany, across all ages, are estimated to be immunologically naïve, highlighting the large impact the first two Omicron waves had until the beginning of summer in 2022. The method developed here might be useful for similar estimations in other countries or future outbreaks of other infectious diseases.

A randomized clinical trial of plasticity-based cognitive training in mild traumatic brain injury.

Clinical practice guidelines support cognitive rehabilitation for people with a history of mild traumatic brain injury (mTBI) and cognitive impairment, but no class I randomized clinical trials have evaluated the efficacy of self-administered computerized cognitive training. The goal of this study was to evaluate the efficacy of a self-administered computerized plasticity-based cognitive training programmes in primarily military/veteran participants with a history of mTBI and cognitive impairment. A multisite randomized double-blind clinical trial of a behavioural intervention with an active control was conducted from September 2013 to February 2017 including assessments at baseline, post-training, and after a 3-month follow-up period. Participants self-administered cognitive training (experimental and active control) programmes at home, remotely supervised by a healthcare coach, with an intended training schedule of 5 days per week, 1 h per day, for 13 weeks. Participants (149 contacted, 83 intent-to-treat) were confirmed to have a history of mTBI (mean of 7.2 years post-injury) through medical history/clinician interview and persistent cognitive impairment through neuropsychological testing and/or quantitative participant reported measure. The experimental intervention was a brain plasticity-based computerized cognitive training programme targeting speed/accuracy of information processing, and the active control was composed of computer games. The primary cognitive function measure was a composite of nine standardized neuropsychological assessments, and the primary directly observed functional measure a timed instrumental activities of daily living assessment. Secondary outcome measures included participant-reported assessments of cognitive and mental health. The treatment group showed an improvement in the composite cognitive measure significantly larger than that of the active control group at both the post-training [+6.9 points, confidence interval (CI) +1.0 to +12.7, P = 0.025, d = 0.555] and the follow-up visit (+7.4 points, CI +0.6 to +14.3, P = 0.039, d = 0.591). Both large and small cognitive function improvements were seen twice as frequently in the treatment group than in the active control group. No significant between-group effects were seen on other measures, including the directly-observed functional and symptom measures. Statistically equivalent improvements in both groups were seen in depressive and cognitive symptoms.

Randomized controlled trial of computer-based treatment of social cognition in schizophrenia: the TRuSST trial protocol.

BACKGROUND: Schizophrenia is a severe and chronic medical condition, characterized by positive and negative symptoms, as well as pervasive social cognitive deficits. Despite the functional significance of the social cognition deficits affecting many aspects of daily living, such as social relationships, occupational status, and independent living, there is still no effective treatment option for these deficits, which is applied as standard of care. To address this need, we developed a novel, internet-based training program that targets social cognition deficits in schizophrenia (SocialVille). Preliminary studies demonstrate the feasibility and initial efficacy of Socialville in schizophrenia patients (Nahum et al., 2014). The purpose of the current trial (referred to as the TReatment of Social cognition in Schizophrenia Trial or TRuSST) is to compare SocialVille to an active control training condition, include a larger sample of patients, and assess both social cognitive functioning, and functional outcomes. METHODS/DESIGN: We will employ a multi-site, longitudinal, blinded, randomized controlled trial (RCT) design with a target sample of 128 patients with schizophrenia. Patients will perform, at their home or in clinic, 40 sessions of either the SocialVille training program or an active control computer game condition. Each session will last for 40-45 minutes/day, performed 3-5 days a week, over 10-12 weeks, totaling to 30 hours of training. Patients will be assessed on a battery of social cognitive, social functioning and functional outcomes immediately before training, mid-way through training (after 20 training sessions) and at the completion of the 40 training sessions. DISCUSSION: The strengths of this protocol are that it tests an innovative, internet-based treatment that targets fundamental social cognitive deficits in schizophrenia, employs a highly sensitive and extensive battery of functional outcome measures, and incorporates a large sample size in an RCT design. TRIAL REGISTRATION: ClinicalTrials.gov NCT02246426 Registered 16 September 2014.

Evidence for positive long- and short-term effects of vaccinations against COVID-19 in wearable sensor metrics.

Vaccines are among the most powerful tools to combat the COVID-19 pandemic. They are highly effective against infection and substantially reduce the risk of severe disease, hospitalization, ICU admission, and death. However, their potential for attenuating long-term changes in personal health and health-related wellbeing after a SARS-CoV-2 infection remains a subject of debate. Such effects can be effectively monitored at the individual level by analyzing physiological data collected by consumer-grade wearable sensors. Here, we investigate changes in resting heart rate, daily physical activity, and sleep duration around a SARS-CoV-2 infection stratified by vaccination status. Data were collected over a period of 2 years in the context of the German Corona Data Donation Project with around 190,000 monthly active participants. Compared to their unvaccinated counterparts, we find that vaccinated individuals, on average, experience smaller changes in their vital data that also return to normal levels more quickly. Likewise, extreme changes in vitals during the acute phase of the disease occur less frequently in vaccinated individuals. Our results solidify evidence that vaccines can mitigate long-term detrimental effects of SARS-CoV-2 infections both in terms of duration and magnitude. Furthermore, they demonstrate the value of large-scale, high-resolution wearable sensor data in public health research.

Modeling the impact of the Omicron infection wave in Germany.

In November 2021, the first infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VOC) B.1.1.529 ('Omicron') was reported in Germany, alongside global reports of reduced vaccine efficacy (VE) against infections with this variant. The potential threat posed by its rapid spread in Germany was, at the time, difficult to predict. We developed a variant-dependent population-averaged susceptible-exposed-infected-recovered infectious-disease model that included information about variant-specific and waning VEs based on empirical data available at the time. Compared to other approaches, our method aimed for minimal structural and computational complexity and therefore enabled us to respond to changes in the situation in a more agile manner while still being able to analyze the potential influence of (non-)pharmaceutical interventions (NPIs) on the emerging crisis. Thus, the model allowed us to estimate potential courses of upcoming infection waves in Germany, focusing on the corresponding burden on intensive care units (ICUs), the efficacy of contact reduction strategies, and the success of the booster vaccine rollout campaign. We expected a large cumulative number of infections with the VOC Omicron in Germany with ICU occupancy likely remaining below capacity, nevertheless, even without additional NPIs. The projected figures were in line with the actual Omicron waves that were subsequently observed in Germany with respective peaks occurring in mid-February and mid-March. Most surprisingly, our model showed that early, strict, and short contact reductions could have led to a strong 'rebound' effect with high incidences after the end of the respective NPIs, despite a potentially successful booster campaign. The results presented here informed legislation in Germany. The methodology developed in this study might be used to estimate the impact of future waves of COVID-19 or other infectious diseases.

Online Social Cognition Training in Schizophrenia: A Double-Blind, Randomized, Controlled Multi-Site Clinical Trial.

Social cognition (SC), the mental operations underlying social functioning, are impaired in schizophrenia. Their direct link to functional outcome and illness status have made them an important therapeutic target. However, no effective treatment for these deficits is currently applied as a standard of care. To address this need, we have developed SocialVille-an online, plasticity-based training program that targets SC deficits in schizophrenia. Here we report the outcomes of a double-blind, controlled, randomized, multi-site clinical trial of SocialVille. Outpatients with schizophrenia were randomized to complete 40 sessions of either SocialVille (N = 55 completers) or active control (computer games; N = 53 completers) from home. The a priori co-primary outcome measures were a social cognitive composite and a functional capacity outcome (UCSD Performance-based Skills Assessment [UPSA-2]). Secondary outcomes included a virtual functional capacity measure (VRFCAT), social functioning, quality of life, and motivation. Linear mixed models revealed a group × time interaction favoring the treatment group for the social cognitive composite (b = 2.81; P < .001) but not for the UPSA-2 measure. Analysis of secondary outcome measures showed significant group × time effects favoring the treatment group on SC and social functioning, on the virtual functional capacity measure and a motivation subscale, although these latter findings were nonsignificant with FDR correction. These results provide support for the efficacy of a remote, plasticity-based social cognitive training program in improving SC and social functioning in schizophrenia. Such treatments may serve as a cost-effective adjunct to existing psychosocial treatments. Trial Registration: NCT02246426.

Evaluation of a plasticity-based cognitive training program in schizophrenia: Results from the eCaesar trial.

OBJECTIVE: Cognitive impairment in schizophrenia is a core feature of the disorder. Computerized cognitive training has shown promise in pilot studies. A 26-week randomized blinded placebo-controlled trial was conducted to investigate the effect of a novel computerized cognitive training program on cognitive and functional capacity outcomes. METHOD: The study followed MATRICS guidelines for the evaluation of interventions designed to improve cognitive function in schizophrenia. Participants (N = 150) were randomized to experimental (computerized cognitive training in a game-like format) or active control (computer games) groups. Training was conducted in-clinic, with an intended training schedule of 5 days per week, 1 h per day, for 26 weeks. Co-primary outcome measures were the MATRICS Consensus Cognitive Battery (MCCB) composite score and the UCSD Performance-Based Skills Assessment (UPSA-2) total score, secondary outcome measures included the Cognitive Assessment Interview (CAI) and the Short-Form-12 Mental Composite Score (SF-12 MCS). Target engagement was assessed with task-learning based assessment. RESULTS: At baseline, the groups were well matched. No significant effect of the experimental treatment was seen on the primary or secondary outcome measures compared to the active control. Review of the task learning/target engagement data suggested inadequate target engagement. CONCLUSIONS: Results do not support a cognitive or functional capacity benefit from this implementation of a computerized cognitive training program in people with schizophrenia. In future trials, careful consideration is merited of the assessment of task learning/target engagement, the effects of making the cognitive training game-like on motivation, and the implicit effects of trial requirements on participant selection.

Prevalence of Positive COVID-19 Test Results Collected by Digital Self-report in the US and Germany.

This cohort study examines traditional surveillance and self-reported COVID-19 test result data collected from independent smartphone app­based studies in the US and Germany.

Ribbon scanning confocal for high-speed high-resolution volume imaging of brain.

Whole-brain imaging is becoming a fundamental means of experimental insight; however, achieving subcellular resolution imagery in a reasonable time window has not been possible. We describe the first application of multicolor ribbon scanning confocal methods to collect high-resolution volume images of chemically cleared brains. We demonstrate that ribbon scanning collects images over ten times faster than conventional high speed confocal systems but with equivalent spectral and spatial resolution. Further, using this technology, we reconstruct large volumes of mouse brain infected with encephalitic alphaviruses and demonstrate that regions of the brain with abundant viral replication were inaccessible to vascular perfusion. This reveals that the destruction or collapse of large regions of brain micro vasculature may contribute to the severe disease caused by Venezuelan equine encephalitis virus. Visualization of this fundamental impact of infection would not be possible without sampling at subcellular resolution within large brain volumes.