Case report: Variant-specific pre-exposure prophylaxis of SARS-CoV-2 infection in multiple sclerosis patients lacking vaccination responses

Sphingosine-1-phosphate receptor modulators and anti-CD20 treatment are widely used disease-modifying treatments for multiple sclerosis. Unfortunately, they may impair the patient’s ability to mount sufficient humoral and T-cellular responses to vaccination, which is of special relevance in the context of the SARS-CoV-2 pandemic. We present here a case series of six multiple sclerosis patients on treatment with sphingosine-1-phosphate receptor modulators who failed to develop SARS-CoV-2-specific antibodies and T-cells after three doses of vaccination. Due to their ongoing immunotherapy, lacking vaccination response, and additional risk factors, we offered them pre-exposure prophylactic treatment with monoclonal SARS-CoV-2-neutralizing antibodies. Initially, treatment was conducted with the antibody cocktail casirivimab/imdevimab. When the SARS-CoV-2 Omicron variant became predominant, we switched treatment to monoclonal antibody sotrovimab due to its sustained neutralizing ability also against the Omicron strain. Since sotrovimab was approved only for the treatment of COVID-19 infection and not for pre-exposure prophylaxis, we switched treatment to tixagevimab/cilgavimab as soon as it was granted marketing authorization in the European Union. This antibody cocktail has retained, albeit reduced, neutralizing activity against the Omicron variant and is approved for pre-exposure prophylaxis. No severe adverse events were recorded for our patients. One patient had a positive RT-PCR for SARS-CoV-2 under treatment with sotrovimab, but was asymptomatic. The other five patients did not develop symptoms of an upper respiratory tract infection or evidence of a SARS-CoV-2 infection during the time of treatment up until the finalization of this report. SARS-CoV-2-neutralizing antibody treatment should be considered individually for multiple sclerosis patients lacking adequate vaccination responses on account of their immunomodulatory treatment, especially in times of high incidences of SARS-CoV-2 infection

Approach to SARS-CoV-2 Vaccination in Patients With Multiple Sclerosis

For more than a year now, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been causing the coronavirus disease (COVID-19) pandemic with high mortality and detrimental effects on society, economy, and individual lives. Great hopes are being placed on vaccination as one of the most potent escape strategies from the pandemic and multiple vaccines are already in clinical use. However, there is still a lot of insecurity about the safety and efficacy of vaccines in patients with autoimmune diseases like multiple sclerosis (MS), especially under treatment with immunomodulatory or immunosuppressive drugs. We propose strategic approaches to SARS-CoV-2 vaccination management in MS patients and encourage fellow physicians to measure the immune response in their patients. Notably, both humoral and cellular responses should be considered since the immunological equivalent for protection from SARS-CoV-2 after infection or vaccination still remains undefined and will most likely involve antiviral cellular immunity. It is important to gain insights into the vaccine response of immunocompromised patients in order to be able to deduce sensible strategies for vaccination in the future

Traces of trauma – a multivariate pattern analysis of childhood trauma, brain structure and clinical phenotypes

Background: Childhood trauma (CT) is a major yet elusive psychiatric risk factor, whose multidimensional conceptualization and heterogeneous effects on brain morphology might demand advanced mathematical modeling. Therefore, we present an unsupervised machine learning approach to characterize the clinical and neuroanatomical complexity of CT in a larger, transdiagnostic context. Methods: We used a multicenter European cohort of 1076 female and male individuals (discovery: n = 649; replication: n = 427) comprising young, minimally medicated patients with clinical high-risk states for psychosis; patients with recent-onset depression or psychosis; and healthy volunteers. We employed multivariate sparse partial least squares analysis to detect parsimonious associations between combinations of items from the Childhood Trauma Questionnaire and gray matter volume and tested their generalizability via nested cross-validation as well as via external validation. We investigated the associations of these CT signatures with state (functioning, depressivity, quality of life), trait (personality), and sociodemographic levels. Results: We discovered signatures of age-dependent sexual abuse and sex-dependent physical and sexual abuse, as well as emotional trauma, which projected onto gray matter volume patterns in prefronto-cerebellar, limbic, and sensory networks. These signatures were associated with predominantly impaired clinical state- and trait-level phenotypes, while pointing toward an interaction between sexual abuse, age, urbanicity, and education. We validated the clinical profiles for all three CT signatures in the replication sample. Conclusions: Our results suggest distinct multilayered associations between partially age- and sex-dependent patterns of CT, distributed neuroanatomical networks, and clinical profiles. Hence, our study highlights how machine learning approaches can shape future, more fine-grained CT research

Long-Term Immune Response Profiles to SARS-CoV-2 Vaccination and Infection in People with Multiple Sclerosis on Anti-CD20 Therapy

Our objective was to analyze longitudinal cellular and humoral immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in people with multiple sclerosis (pwMS) on B-cell depleting treatment (BCDT) compared to pwMS without immunotherapy. We further evaluated the impact of COVID-19 infection and vaccination timing. PwMS (n = 439) on BCDT (ocrelizumab, rituximab, ofatumumab) or without immunotherapy were recruited for this prospective cohort study between June 2021 and June 2022. SARS-CoV-2 spike-specific antibodies and interferon-γ release of CD4 and CD8 T-cells upon stimulation with spike protein peptide pools were analyzed at different timepoints (after primary vaccination, 3 and 6 months after primary vaccination, after booster vaccination, 3 months after booster). Humoral response to SARS-CoV-2 was consistently lower whereas T-cell response was higher in patients with BCDT compared to controls. Cellular and humoral responses decreased over time after primary vaccination and increased again upon booster vaccination, with significantly higher antibody titers after booster than after primary vaccination in both untreated and B-cell-depleted pwMS. COVID-19 infection further led to a significant increase in SARS-CoV-2-specific responses. Despite attenuated B-cell responses, a third vaccination for patients with BCDT seems recommendable, since at least partial protection can be expected from the strong T-cell response. Moreover, our data show that an assessment of T-cell responses may be helpful in B-cell-depleted patients to evaluate the efficacy of SARS-CoV-2 vaccination

Motor Improvement and Emotional Stabilization in Patients With Tourette Syndrome After Deep Brain Stimulation of the Ventral Anterior and Ventrolateral Motor Part of the Thalamus

BACKGROUND: Since its first application in 1999, the potential benefit of deep brain stimulation (DBS) in reducing symptoms of otherwise treatment-refractory Tourette syndrome (TS) has been documented in several publications. However, uncertainty regarding the ideal neural targets remains, and the eventuality of so far undocumented but possible negative long-term effects on personality fuels the debate about the ethical implications of DBS. METHODS: In this prospective open-label trial, eight patients (three female, five male) 19-56 years old with severe and medically intractable TS were treated with high-frequency DBS of the ventral anterior and ventrolateral motor part of the thalamus. To assess the course of TS, its clinical comorbidities, personality parameters, and self-perceived quality of life, patients underwent repeated psychiatric assessments at baseline and 6 and 12 months after DBS onset. RESULTS: Analysis indicated a strongly significant and beneficial effect of DBS on TS symptoms, trait anxiety, quality of life, and global functioning with an apparently low side-effect profile. In addition, presurgical compulsivity, anxiety, emotional dysregulation, and inhibition appeared to be significant predictors of surgery outcome. CONCLUSIONS: Trading off motor effects and desirable side effects against surgery-related risks and negative implications, stimulation of the ventral anterior and ventrolateral motor part of the thalamus seems to be a valuable option when considering DBS for TS

The effects of webcams on German neonatal intensive care units - study protocol of a randomised crossover trial (Neo-CamCare)

Background: The separation of parents and their prematurely born children during care in a neonatal intensive care unit (NICU) can have far-reaching consequences for the well-being of the parents and also of the children. The aim of this study is to evaluate the use of webcams on NICUs and to conduct a systematic assessment of their possible effects on parents and clinical staff. In addition, it aims at determining the need for webcams in German NICUs and to identify possible barriers and moderators. The development and evaluation of practical guidance for the use of webcams will enable the comprehensive education of clinical staff and parents and, as a result, is intended to mitigate any potential undesirable consequences. Methods: The study will be based on a mixed methods approach including all groups concerned in the care. Qualitative data will be collected in interviews and focus groups and evaluated using content analysis. The collection of quantitative data will be based on written questionnaires and will aim to assess the status quo as regards the use of webcams on German NICUs and the effects on parents, physicians, and nursing staff. These effects will be assessed in a randomised cross-over design. Four NICUs will be involved in the study and, in total, the parents of 730 premature babies will be invited to take part in the study. The effects on the nursing staff, such as additional workload and interruptions in workflows, will be evaluated on the basis of observation data. Discussion: This study will be the largest multicentre study known to us that systematically evaluates the use of webcams in neonatal intensive care units. The effects of the implementation of webcams on both parents and care providers will be considered. The results provide evidence to decide whether to promote the use of webcams on NICUs or not and what to consider when implementing them

Validation of the Bullying Scale for Adults - Results of the PRONIA-study

Background: Bullying as a specific subtype of adverse life events is a major risk factor for poor mental health. Although many questionnaires on bullying are available, so far none covers bullying retrospectively throughout school and working life. To close this gap, the Bullying Scale for Adults (BSA) was designed. Methods: Based on data of 622 participants from five European countries collected in the prospective multicenter Personalized Prognostic Tools for Early Psychosis Management (PRONIA) study, we investigated whether the BSA is a reliable and valid measurement for bullying and whether there is a difference across different diagnostic groups of early mental disorders (recent onset depressive/psychotic patients, patients at clinical high-risk of psychosis) and healthy controls. Results: Bullying experiences were significantly less frequent in healthy controls than in patient groups, with no significant differences between the three clinical groups. The BSA exhibited a high item scale discrimination (r > .3) and very good internal consistency (Cronbach's alpha = .93). Four factors were identified: 1. Sexual harassment, 2. Emotional Abuse, 3. Physical Abuse, 4. Problems at school. The highly significant correlation between bullying, and childhood adversities and trauma (r = .645, p < .001) indicated good concurrent validity. Discussion: The BSA is the first validated questionnaire that, in retrospective, reliably records various aspects of bullying (incl. its consequences) not only throughout childhood but also working life. It can be used to assess bullying as a transdiagnostic risk factor of mental disorders in different mental disorders, esp. psychosis and depression

Association between age of cannabis initiation and gray matter covariance networks in recent onset psychosis

Cannabis use during adolescence is associated with an increased risk of developing psychosis. According to a current hypothesis, this results from detrimental effects of early cannabis use on brain maturation during this vulnerable period. However, studies investigating the interaction between early cannabis use and brain structural alterations hitherto reported inconclusive findings. We investigated effects of age of cannabis initiation on psychosis using data from the multicentric Personalized Prognostic Tools for Early Psychosis Management (PRONIA) and the Cannabis Induced Psychosis (CIP) studies, yielding a total sample of 102 clinically-relevant cannabis users with recent onset psychosis. GM covariance underlies shared maturational processes. Therefore, we performed source-based morphometry analysis with spatial constraints on structural brain networks showing significant alterations in schizophrenia in a previous multisite study, thus testing associations of these networks with the age of cannabis initiation and with confounding factors. Earlier cannabis initiation was associated with more severe positive symptoms in our cohort. Greater gray matter volume (GMV) in the previously identified cerebellar schizophrenia-related network had a significant association with early cannabis use, independent of several possibly confounding factors. Moreover, GMV in the cerebellar network was associated with lower volume in another network previously associated with schizophrenia, comprising the insula, superior temporal, and inferior frontal gyrus. These findings are in line with previous investigations in healthy cannabis users, and suggest that early initiation of cannabis perturbs the developmental trajectory of certain structural brain networks in a manner imparting risk for psychosis later in life.</p