Persistence of immunity to SARS-CoV-2 over time in the ski resort Ischgl

Background In early March 2020, a SARS-CoV-2 outbreak in the ski resort Ischgl in Austria triggered the spread of SARS-CoV-2 throughout Austria and Northern Europe. In a previous study, we found that the seroprevalence in the adult population of Ischgl had reached 45% by the end of April, representing an exceptionally high level of local seropositivity in Europe. We performed a follow-up study in Ischgl, which is the first to show persistence of immunity and protection against SARS-CoV-2 and some of its variants at a community level. Methods Of the 1259 adults that participated in the baseline study, 801 have been included in the follow-up in November 2020. The study involved the analysis of binding and neutralizing antibodies and T cell responses. In addition, the incidence of SARS-CoV-2 and its variants in Ischgl was compared to the incidence in similar municipalities in Tyrol until April 2021. Findings For the 801 individuals that participated in both studies, the seroprevalence declined from 51.4% (95% confidence interval (CI) 47.9-54.9) to 45.4% (95% CI 42.0-49.0). Median antibody concentrations dropped considerably (5.345, 95% CI 4.833 - 6.123 to 2.298, 95% CI 2.141 - 2.527) but antibody avidity increased (17.02, 95% CI 16.49 - 17.94 to 42.46, 95% CI 41.06 - 46.26). Only one person had lost detectable antibodies and T cell responses. In parallel to this persistent immunity, we observed that Ischgl was relatively spared, compared to similar municipalities, from the prominent second COVID-19 wave that hit Austria in November 2020. In addition, we used sequencing data to show that the local immunity acquired from wild-type infections also helped to curb infections from variants of SARS-CoV-2 which spread in Austria since January 2021. Interpretation The relatively high level of seroprevalence (40-45%) in Ischgl persisted and might have been associated with the observed protection of Ischgl residents against virus infection during the second COVID-19 wave as well as against variant spread in 2021. Funding Funding was provided by the government of Tyrol and the FWF Austrian Science Fund

High prevalence group testing in epidemiology with geometrically inspired algorithms

Abstract Demand for mass surveillance during peak times of the SARS-CoV-2 pandemic caused high workload for clinical laboratories. Efficient and cost conserving testing designs by means of group testing can substantially reduce resources during possible future emergency situations. The novel hypercube algorithm proposed by Mutesa et al. 2021 published in Nature provides methodological proof of concept and points out the applicability to epidemiological testing. In this work, the algorithm is explored and expanded for settings with high group prevalence. Numerical studies investigate the limits of the adapted hypercube methodology, allowing to optimize pooling designs for specific requirements (i.e. number of samples and group prevalence). Hyperparameter optimization is performed to maximize test-reduction. Standard deviation is examined to investigate resilience and precision. Moreover, empirical validation was performed by elaborately pooling SARS-CoV-2 virus samples according to numerically optimized pooling designs. Laboratory experiments with SARS-CoV-2 sample groups, ranging from 50 to 200 items, characterized by group prevalence up to 10%, are successfully processed and analysed. Test-reductions from 50 to 72.5% were achieved in the experimental setups when compared to individual testing. Higher theoretical test-reduction is possible, depending on the number of samples and the group prevalence, indicated by simulation results

Systemic Inflammation and Complement Activation Parameters Predict Clinical Outcome of Severe SARS-CoV-2 Infections

Overactivation of the complement system has been characterized in severe COVID-19 cases. Complement components are known to trigger NETosis via the coagulation cascade and have also been reported in human tracheobronchial epithelial cells. In this longitudinal study, we investigated systemic and local complement activation and NETosis in COVID-19 patients that underwent mechanical ventilation. Results confirmed significantly higher baseline levels of serum C5a (24.5 ± 39.0 ng/mL) and TCC (11.03 ± 8.52 µg/mL) in patients compared to healthy controls (p p 6 neutrophils/mL) compared to healthy controls (0.82 (±0.74) × 106 neutrophils/mL) (p < 0.0001). In tracheal fluid, baseline TCC levels but not C5a and NETosis, were significantly higher in patients. Kinetic studies of systemic complement activation revealed markedly higher levels of TCC and CRP in nonsurvivors compared to survivors. In contrast, kinetic studies showed decreased local NETosis in tracheal fluid but comparable local complement activation in nonsurvivors compared to survivors. Systemic TCC and NETosis were significantly correlated with inflammation and coagulation markers. We propose that a ratio comprising systemic inflammation, complement activation, and chest X-ray score could be rendered as a predictive parameter of patient outcome in severe SARS-CoV-2 infections

Characterizing SARS-CoV-2 neutralization profiles after bivalent boosting using antigenic cartography.

Since emergence of the initial SARS-CoV-2 BA.1, BA.2 and BA.5 variants, Omicron has diversified substantially. Antigenic characterization of these new variants is important to analyze their potential immune escape from population immunity and implications for future vaccine composition. Here, we describe an antigenic map based on human single-exposure sera and live-virus isolates that includes a broad selection of recently emerged Omicron variants such as BA.2.75, BF.7, BQ, XBB and XBF variants. Recent Omicron variants clustered around BA.1 and BA.5 with some variants further extending the antigenic space. Based on this antigenic map we constructed antibody landscapes to describe neutralization profiles after booster immunization with bivalent mRNA vaccines based on ancestral virus and either BA.1 or BA.4/5. Immune escape of BA.2.75, BQ, XBB and XBF variants was also evident in bivalently boosted individuals, however, cross-neutralization was improved for those with hybrid immunity. Our results indicate that future vaccine updates are needed to induce cross-neutralizing antibodies against currently circulating variants

Characterizing SARS-CoV-2 neutralization profiles after bivalent boosting using antigenic cartography.

Since emergence of the initial SARS-CoV-2 BA.1, BA.2 and BA.5 variants, Omicron has diversified substantially. Antigenic characterization of these new variants is important to analyze their potential immune escape from population immunity and implications for future vaccine composition. Here, we describe an antigenic map based on human single-exposure sera and live-virus isolates that includes a broad selection of recently emerged Omicron variants such as BA.2.75, BF.7, BQ, XBB and XBF variants. Recent Omicron variants clustered around BA.1 and BA.5 with some variants further extending the antigenic space. Based on this antigenic map we constructed antibody landscapes to describe neutralization profiles after booster immunization with bivalent mRNA vaccines based on ancestral virus and either BA.1 or BA.4/5. Immune escape of BA.2.75, BQ, XBB and XBF variants was also evident in bivalently boosted individuals, however, cross-neutralization was improved for those with hybrid immunity. Our results indicate that future vaccine updates are needed to induce cross-neutralizing antibodies against currently circulating variants

Characterizing SARS-CoV-2 neutralization profiles after bivalent boosting using antigenic cartography

Acknowledgements: We thank Albert Falch, Verena Pittl, Maria Huber, Anna Sauerwein, Anne Heberle, and Toni Rabensteiner for excellent technical and organizational support. We thank Prof. Florian Krammer and Prof. Viviana Simon for sharing their Delta isolate and Prof. Oliver T. Keppler and Dr. Marcel Stern for sharing their Gamma isolate with us. The European Union’s Horizon 2020 research and innovation program under grant agreement No. 101016174 and the Austrian Science Fund (FWF) with project number P35159-B supported J.K. The NIH NIAID Centers of Excellence for Influenza Research and Response (CEIRR) contract 75N93021C00014 as part of the SAVE program supported J.K., D.S., and A.N. A.N. was supported by the Gates Cambridge Trust.Funder: European Union’s Horizon 2020 research and innovation program under grant agreement No. 101016174 NIH NIAID Centers of Excellence for Influenza Research and Response (CEIRR) contract 75N93021C00014 as part of the SAVE programFunder: Gates Cambridge Trust; doi: https://doi.org/10.13039/501100005370Since emergence of the initial SARS-CoV-2 BA.1, BA.2 and BA.5 variants, Omicron has diversified substantially. Antigenic characterization of these new variants is important to analyze their potential immune escape from population immunity and implications for future vaccine composition. Here, we describe an antigenic map based on human single-exposure sera and live-virus isolates that includes a broad selection of recently emerged Omicron variants such as BA.2.75, BF.7, BQ, XBB and XBF variants. Recent Omicron variants clustered around BA.1 and BA.5 with some variants further extending the antigenic space. Based on this antigenic map we constructed antibody landscapes to describe neutralization profiles after booster immunization with bivalent mRNA vaccines based on ancestral virus and either BA.1 or BA.4/5. Immune escape of BA.2.75, BQ, XBB and XBF variants was also evident in bivalently boosted individuals, however, cross-neutralization was improved for those with hybrid immunity. Our results indicate that future vaccine updates are needed to induce cross-neutralizing antibodies against currently circulating variants

Characterizing SARS-CoV-2 neutralization profiles after bivalent boosting using antigenic cartography

Acknowledgements: We thank Albert Falch, Verena Pittl, Maria Huber, Anna Sauerwein, Anne Heberle, and Toni Rabensteiner for excellent technical and organizational support. We thank Prof. Florian Krammer and Prof. Viviana Simon for sharing their Delta isolate and Prof. Oliver T. Keppler and Dr. Marcel Stern for sharing their Gamma isolate with us. The European Union’s Horizon 2020 research and innovation program under grant agreement No. 101016174 and the Austrian Science Fund (FWF) with project number P35159-B supported J.K. The NIH NIAID Centers of Excellence for Influenza Research and Response (CEIRR) contract 75N93021C00014 as part of the SAVE program supported J.K., D.S., and A.N. A.N. was supported by the Gates Cambridge Trust.Funder: European Union’s Horizon 2020 research and innovation program under grant agreement No. 101016174 NIH NIAID Centers of Excellence for Influenza Research and Response (CEIRR) contract 75N93021C00014 as part of the SAVE programFunder: Gates Cambridge Trust; doi: https://doi.org/10.13039/501100005370Since emergence of the initial SARS-CoV-2 BA.1, BA.2 and BA.5 variants, Omicron has diversified substantially. Antigenic characterization of these new variants is important to analyze their potential immune escape from population immunity and implications for future vaccine composition. Here, we describe an antigenic map based on human single-exposure sera and live-virus isolates that includes a broad selection of recently emerged Omicron variants such as BA.2.75, BF.7, BQ, XBB and XBF variants. Recent Omicron variants clustered around BA.1 and BA.5 with some variants further extending the antigenic space. Based on this antigenic map we constructed antibody landscapes to describe neutralization profiles after booster immunization with bivalent mRNA vaccines based on ancestral virus and either BA.1 or BA.4/5. Immune escape of BA.2.75, BQ, XBB and XBF variants was also evident in bivalently boosted individuals, however, cross-neutralization was improved for those with hybrid immunity. Our results indicate that future vaccine updates are needed to induce cross-neutralizing antibodies against currently circulating variants

Characterizing SARS-CoV-2 neutralization profiles after bivalent boosting using antigenic cartography

Abstract Since emergence of the initial SARS-CoV-2 BA.1, BA.2 and BA.5 variants, Omicron has diversified substantially. Antigenic characterization of these new variants is important to analyze their potential immune escape from population immunity and implications for future vaccine composition. Here, we describe an antigenic map based on human single-exposure sera and live-virus isolates that includes a broad selection of recently emerged Omicron variants such as BA.2.75, BF.7, BQ, XBB and XBF variants. Recent Omicron variants clustered around BA.1 and BA.5 with some variants further extending the antigenic space. Based on this antigenic map we constructed antibody landscapes to describe neutralization profiles after booster immunization with bivalent mRNA vaccines based on ancestral virus and either BA.1 or BA.4/5. Immune escape of BA.2.75, BQ, XBB and XBF variants was also evident in bivalently boosted individuals, however, cross-neutralization was improved for those with hybrid immunity. Our results indicate that future vaccine updates are needed to induce cross-neutralizing antibodies against currently circulating variants

Outbreak report: a nosocomial outbreak of vancomycin resistant enterococci in a solid organ transplant unit

Abstract Background Vancomycin resistant enterococci (VRE) are an emerging problem in health care settings. The purpose of the investigation was to assess the extent of the outbreak including environmental contamination and to limit further transmission. Methods We used retrospective patient and laboratory data including pulse field gel electrophoresis (PFGE) typing and virulence and resistance gene analysis. For comparison of medians the Mann-Whitney and for comparison of proportions the Fisher exact tests were used. Results PFGE typing of VRE strains of an outbreak of 15 VRE cases in a solid transplant unit revealed that nine of the cases belonged to one identical pattern (A), which was only found twice in the environment. Eleven further positive environmental samples showed a different, but identical PFGE pattern E. Only one patient was infected with this environmental strain. Two of nine (22.2%) PFGE A, but nine of eleven (81.2%) PFGE E samples were positive for gelatinase E (p = 0.01), which is described as enhancing biofilm production, suggesting a survival benefit for this strain on inanimate surfaces. Conclusion Routine disinfection was not able to stop the cluster, but after repeated enforcement of the infection prevention and control (IPC) bundle such as training, strict adherence to hand hygiene and surface disinfection no further cases were observed. We conclude that certain VRE strains predominate in the environment whereas others predominate in humans. Enforcement of the IPC bundle is essential for controlling VRE outbreaks and reducing further transmission

BA.2 and BA.5 omicron differ immunologically from both BA.1 omicron and pre-omicron variants.

Several studies have shown that SARS-CoV-2 BA.1 omicron is an immune escape variant. Meanwhile, however, omicron BA.2 and BA.5 became dominant in many countries and replaced BA.1. As both have several mutations compared to BA.1, we analyzed whether BA.2 and BA.5 show further immune escape relative to BA.1. Here, we characterized neutralization profiles against the BA.2 and BA.5 omicron sub-variants in plasma samples from individuals with different history of exposures to infection/vaccination and found that unvaccinated individuals after a single exposure to BA.2 had limited cross-neutralizing antibodies to pre-omicron variants and to BA.1. Consequently, our antigenic map including all Variants of Concern and BA.1, BA.2 and BA.5 omicron sub-variants, showed that all omicron sub-variants are distinct to pre-omicron variants, but that the three omicron variants are also antigenically distinct from each other. The antibody landscapes illustrate that cross-neutralizing antibodies against the current antigenic space, as described in our maps, are generated only after three or more exposures to antigenically close variants but also after two exposures to antigenically distant variants. Here, we describe the antigenic space inhabited by the relevant SARS-CoV-2 variants, the understanding of which will have important implications for further vaccine strain adaptations