Enhanced Spike-specific, but attenuated Nucleocapsid-specific T cell responses upon SARS-CoV-2 breakthrough versus non-breakthrough infections

SARS-CoV-2 vaccine breakthrough infections frequently occurred even before the emergence of Omicron variants. Yet, relatively little is known about the impact of vaccination on SARS-CoV-2-specific T cell and antibody response dynamics upon breakthrough infection. We have therefore studied the dynamics of CD4 and CD8 T cells targeting the vaccine-encoded Spike and the non-encoded Nucleocapsid antigens during breakthrough infections (BTI, n=24) and in unvaccinated control infections (non-BTI, n=30). Subjects with vaccine breakthrough infection had significantly higher CD4 and CD8 T cell responses targeting the vaccine-encoded Spike during the first and third/fourth week after PCR diagnosis compared to non-vaccinated controls, respectively. In contrast, CD4 T cells targeting the non-vaccine encoded Nucleocapsid antigen were of significantly lower magnitude in BTI as compared to non-BTI. Hence, previous vaccination was linked to enhanced T cell responses targeting the vaccine-encoded Spike antigen, while responses against the non-vaccine encoded Nucleocapsid antigen were significantly attenuated

Revascularisation aiguë en cas d'accident vasculaire cérébral ischémique

Au cours des dix dernières années, il a été prouvé scientifiquement que la revascularisation aiguë en cas d’accident vasculaire cérébral ischémique fait partie des traitements les plus efficaces de la médecine aiguë si des critères stricts sont appliqués. Afin d’obtenir le meilleur rapport bénéfice-risque possible pour les patients touchés, la Société Cérébrovasculaire Suisse, en collaboration avec ses sociétés de discipline partenaires, a révisé les lignes directrices correspondantes en tenant compte des nouvelles données scientifiques

Enhanced Spike-specific, but attenuated Nucleocapsid-specific T cell responses upon SARS-CoV-2 breakthrough versus non-breakthrough infections

SARS-CoV-2 vaccine breakthrough infections frequently occurred even before the emergence of Omicron variants. Yet, relatively little is known about the impact of vaccination on SARS-CoV-2-specific T cell and antibody response dynamics upon breakthrough infection. We have therefore studied the dynamics of CD4 and CD8 T cells targeting the vaccine-encoded Spike and the non-encoded Nucleocapsid antigens during breakthrough infections (BTI, n=24) and in unvaccinated control infections (non-BTI, n=30). Subjects with vaccine breakthrough infection had significantly higher CD4 and CD8 T cell responses targeting the vaccine-encoded Spike during the first and third/fourth week after PCR diagnosis compared to non-vaccinated controls, respectively. In contrast, CD4 T cells targeting the non-vaccine encoded Nucleocapsid antigen were of significantly lower magnitude in BTI as compared to non-BTI. Hence, previous vaccination was linked to enhanced T cell responses targeting the vaccine-encoded Spike antigen, while responses against the non-vaccine encoded Nucleocapsid antigen were significantly attenuated

Longitudinal effects of SARS-CoV-2 breakthrough infection on imprinting of neutralizing antibody responses

Background The impact of the infecting SARS-CoV-2 variant of concern (VOC) and the vaccination status was determined on the magnitude, breadth, and durability of the neutralizing antibody (nAb) profile in a longitudinal multicentre cohort study. Methods 173 vaccinated and 56 non-vaccinated individuals were enrolled after SARS-CoV-2 Alpha, Delta, or Omicron infection and visited four times within 6 months and nAbs were measured for D614G, Alpha, Delta, BA.1, BA.2, BA.5, BQ.1.1, XBB.1.5 and JN.1. Findings Magnitude-breadth-analysis showed enhanced neutralization capacity in vaccinated individuals against multiple VOCs. Longitudinal analysis revealed sustained neutralization magnitude-breadth after antigenically distant Delta or Omicron breakthrough infection (BTI), with triple-vaccinated individuals showing significantly elevated titres and improved breadth. Antigenic mapping and antibody landscaping revealed initial boosting of vaccine-induced WT-specific responses after BTI, a shift in neutralization towards infecting VOCs at peak responses and an immune imprinted bias towards dominating WT immunity in the long-term. Despite that bias, machine-learning models confirmed a sustained shift of the immune-profiles following BTI. Interpretation In summary, our longitudinal analysis revealed delayed and short lived nAb shifts towards the infecting VOC, but an immune imprinted bias towards long-term vaccine induced immunity after BTI. Funding This work was funded by the Bavarian State Ministry of Science and the Arts for the CoVaKo study and the ForCovid project. The funders had no influence on the study design, data analysis or data interpretation

Longitudinal effects of SARS-CoV-2 breakthrough infection on imprinting of neutralizing antibody responses

Background The impact of the infecting SARS-CoV-2 variant of concern (VOC) and the vaccination status was determined on the magnitude, breadth, and durability of the neutralizing antibody (nAb) profile in a longitudinal multicentre cohort study. Methods 173 vaccinated and 56 non-vaccinated individuals were enrolled after SARS-CoV-2 Alpha, Delta, or Omicron infection and visited four times within 6 months and nAbs were measured for D614G, Alpha, Delta, BA.1, BA.2, BA.5, BQ.1.1, XBB.1.5 and JN.1. Findings Magnitude-breadth-analysis showed enhanced neutralization capacity in vaccinated individuals against multiple VOCs. Longitudinal analysis revealed sustained neutralization magnitude-breadth after antigenically distant Delta or Omicron breakthrough infection (BTI), with triple vaccinated individuals showing significantly elevated titres and improved breadth. Antigenic mapping and antibody landscaping revealed initial boosting of vaccine-induced WT-specific responses after BTI, a shift in neutralization towards infecting VOCs at peak responses and an immune imprinted bias towards dominating WT immunity in the long-term. Despite that bias, machine-learning models confirmed a sustained shift of the immune-profiles following BTI. Interpretation In summary, our longitudinal analysis revealed delayed and short lived nAb shifts towards the infecting VOC, but an immune imprinted bias towards long-term vaccine induced immunity after BTI. Funding This work was funded by the Bavarian State Ministry of Science and the Arts for the CoVaKo study and the ForCovid project. The funders had no influence on the study design, data analysis or data interpretation

Case report: Experience with the Cube Navigation System in complex access routes during CT-guided lumbosacral infiltration therapy

PurposeComputed tomography (CT)-guided infiltrations are a mainstay in the treatment of lower back pain. Needle placement is usually performed using the free-hand method, where the translation from the planned needle angle to the actual needle insertion angle is estimated. However, the free-hand method is especially challenging in cases where a double-oblique access route (out-of-plane) rather than an in-plane route is necessary. In this case series, we report our experience with the patient-mounted Cube Navigation System to guide needle placement for complex access routes in lumbar pain therapy.Research design and methodsWe retrospectively analyzed the cases of five patients in whom a double-oblique access route was necessary for CT-guided lumbar infiltration pain treatment. Each of those procedures was done using the Cube Navigation System to provide navigational guidance. The mean patient age was 69 ± 13 years (range 58–82 years; all females). Technical success, procedure time, and number of control scans were determined retrospectively.ResultsTechnical success (i.e., positioning and accuracy) was obtained in all cases. Mean procedure time was 15 ± 7 min (10–22 min); on average, 2 ± 1 CT control scans were performed. There were no complications or material failures reported in the present study.ConclusionDouble-oblique punctures with the Cube Navigation System in this initial case series of complex access routes at the lumbar spine were accurate and the procedure was time efficient. In the authors’ view, the Cube Navigation System has the potential to improve needle guidance for complex access routes, especially considering the ease of use of the device.</jats:sec

Frequently Suspected, Rarely Confirmed: The Complex Diagnostic Journey of Adult-Onset MELAS&mdash;Clinical Evaluation and Cost Implications

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a rare mitochondrial disorder primarily presenting in pediatric patients, with onset after 40 years being exceptionally rare (1&ndash;6%). Here, we report a complex diagnostic journey of a 47-year-old male presenting with new-onset seizures, hemiparesis, and neurocognitive deficits. Initial work-up, including MRI, CSF analysis, and extensive antibody screening, yielded inconclusive results, prompting differential considerations such as autoimmune encephalitis and neoplastic conditions. Finally muscle biopsy findings, coupled with genetic confirmation of the m.3243A&gt;G mutation in the MT-TL1 gene, ultimately established the diagnosis of MELAS. This case depicts the atypical presentation of adult-onset MELAS without initial lactic acidemia, diabetes, or hearing impairment. The prolonged diagnostic process underscores the challenges of identifying rare diseases under today&rsquo;s financial and administrative constraints. Still ee emphasize the importance of comprehensive diagnostics in rare cases to advance generall understanding and improve future patient outcomes, also amidst resource limitations