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1. XR Prototyping of Mixed Reality Visualizations: Compensating Interaction Latency for a Medical Imaging Robot

Author

Plümer, Jan Hendrik, Yu, Kevin, Eck, Ulrich, Kalkofen, Denis, Steininger, Philipp, Navab, Nassir, and Tatzgern, Markus

Subjects
Computer Science - Human-Computer Interaction
Abstract

Researching novel user experiences in medicine is challenging due to limited access to equipment and strict ethical protocols. Extended Reality (XR) simulation technologies offer a cost- and time-efficient solution for developing interactive systems. Recent work has shown Extended Reality Prototyping (XRP)'s potential, but its applicability to specific domains like controlling complex machinery needs further exploration. This paper explores the benefits and limitations of XRP in controlling a mobile medical imaging robot. We compare two XR visualization techniques to reduce perceived latency between user input and robot activation. Our XRP validation study demonstrates its potential for comparative studies, but identifies a gap in modeling human behavior in the analytic XRP validation framework.

Published
2024

2. CBCTLiTS: A Synthetic, Paired CBCT/CT Dataset For Segmentation And Style Transfer

Author

Tschuchnig, Maximilian E., Steininger, Philipp, and Gadermayr, Michael

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

Medical imaging is vital in computer assisted intervention. Particularly cone beam computed tomography (CBCT) with defacto real time and mobility capabilities plays an important role. However, CBCT images often suffer from artifacts, which pose challenges for accurate interpretation, motivating research in advanced algorithms for more effective use in clinical practice. In this work we present CBCTLiTS, a synthetically generated, labelled CBCT dataset for segmentation with paired and aligned, high quality computed tomography data. The CBCT data is provided in 5 different levels of quality, reaching from a large number of projections with high visual quality and mild artifacts to a small number of projections with severe artifacts. This allows thorough investigations with the quality as a degree of freedom. We also provide baselines for several possible research scenarios like uni- and multimodal segmentation, multitask learning and style transfer followed by segmentation of relatively simple, liver to complex liver tumor segmentation. CBCTLiTS is accesssible via https://www.kaggle.com/datasets/maximiliantschuchnig/cbct-liver-and-liver-tumor-segmentation-train-data., Comment: Accepted at VCBM 2024 - https://conferences.eg.org/vcbm2024/

Published
2024

3. Multimodal Learning With Intraoperative CBCT & Variably Aligned Preoperative CT Data To Improve Segmentation

Author

Tschuchnig, Maximilian E., Steininger, Philipp, and Gadermayr, Michael

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition, Computer Science - Machine Learning
Abstract

Cone-beam computed tomography (CBCT) is an important tool facilitating computer aided interventions, despite often suffering from artifacts that pose challenges for accurate interpretation. While the degraded image quality can affect downstream segmentation, the availability of high quality, preoperative scans represents potential for improvements. Here we consider a setting where preoperative CT and intraoperative CBCT scans are available, however, the alignment (registration) between the scans is imperfect. We propose a multimodal learning method that fuses roughly aligned CBCT and CT scans and investigate the effect of CBCT quality and misalignment on the final segmentation performance. For that purpose, we make use of a synthetically generated data set containing real CT and synthetic CBCT volumes. As an application scenario, we focus on liver and liver tumor segmentation. We show that the fusion of preoperative CT and simulated, intraoperative CBCT mostly improves segmentation performance (compared to using intraoperative CBCT only) and that even clearly misaligned preoperative data has the potential to improve segmentation performance., Comment: Submitted to SASHIMI2024 (MICCAI workshop)

Published
2024

4. Multi-task Learning To Improve Semantic Segmentation Of CBCT Scans Using Image Reconstruction

Author

Tschuchnig, Maximilian Ernst, Coste-Marin, Julia, Steininger, Philipp, and Gadermayr, Michael

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition
Abstract

Semantic segmentation is a crucial task in medical image processing, essential for segmenting organs or lesions such as tumors. In this study we aim to improve automated segmentation in CBCTs through multi-task learning. To evaluate effects on different volume qualities, a CBCT dataset is synthesised from the CT Liver Tumor Segmentation Benchmark (LiTS) dataset. To improve segmentation, two approaches are investigated. First, we perform multi-task learning to add morphology based regularization through a volume reconstruction task. Second, we use this reconstruction task to reconstruct the best quality CBCT (most similar to the original CT), facilitating denoising effects. We explore both holistic and patch-based approaches. Our findings reveal that, especially using a patch-based approach, multi-task learning improves segmentation in most cases and that these results can further be improved by our denoising approach., Comment: Accepted at German Conference on Medical Image Computing (BVM) 2024

Published
2023

7. First clinical application of image-guided intraoperative electron radiation therapy with real time intraoperative dose calculation in recurrent rectal cancer: technical procedure

Author

Roeder, Falk, Fastner, Gerd, Fussl, Christoph, Sedlmayer, Felix, Stana, Markus, Berchtold, Johannes, Jäger, Tarkan, Presl, Jaroslav, Schredl, Philipp, Emmanuel, Klaus, Colleselli, Daniela, Kotolacsi, Gabriel, Scherer, Philipp, Steininger, Philipp, and Gaisberger, Christoph

Published
2023
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10. Clinical and immunological benefits of full primary COVID-19 vaccination in individuals with SARS-CoV-2 breakthrough infections: A prospective cohort study in non-hospitalized adults

Author

Prelog, Martina, Jeske, Samuel D., Asam, Claudia, Fuchs, Andre, Wieser, Andreas, Gall, Christine, Wytopil, Monika, Mueller-Schmucker, Sandra M., Beileke, Stephanie, Goekkaya, Mehmet, Kling, Elisabeth, Geldmacher, Christof, Rubio-Acero, Raquel, Plank, Michael, Christa, Catharina, Willmann, Annika, Vu, Martin, Einhauser, Sebastian, Weps, Manuela, Lampl, Benedikt M.J., Almanzar, Giovanni, Kousha, Kimia, Schwägerl, Valeria, Liebl, Bernhard, Weber, Beatrix, Drescher, Johannes, Scheidt, Jörg, Gefeller, Olaf, Messmann, Helmut, Protzer, Ulrike, Liese, Johannes, Hoelscher, Michael, Wagner, Ralf, Überla, Klaus, and Steininger, Philipp

Published
2024
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11. Three exposures to the spike protein of SARS-CoV-2 by either infection or vaccination elicit superior neutralizing immunity to all variants of concern

Author

Wratil, Paul R., Stern, Marcel, Priller, Alina, Willmann, Annika, Almanzar, Giovanni, Vogel, Emanuel, Feuerherd, Martin, Cheng, Cho-Chin, Yazici, Sarah, Christa, Catharina, Jeske, Samuel, Lupoli, Gaia, Vogt, Tim, Albanese, Manuel, Mejías-Pérez, Ernesto, Bauernfried, Stefan, Graf, Natalia, Mijocevic, Hrvoje, Vu, Martin, Tinnefeld, Kathrin, Wettengel, Jochen, Hoffmann, Dieter, Muenchhoff, Maximilian, Daechert, Christopher, Mairhofer, Helga, Krebs, Stefan, Fingerle, Volker, Graf, Alexander, Steininger, Philipp, Blum, Helmut, Hornung, Veit, Liebl, Bernhard, Überla, Klaus, Prelog, Martina, Knolle, Percy, Keppler, Oliver T., and Protzer, Ulrike

Published
2022
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14. Adaptive immune responses are larger and functionally preserved in a hypervaccinated individual

Author

Kocher, Katharina, primary, Moosmann, Carolin, additional, Drost, Felix, additional, Schülein, Christine, additional, Irrgang, Pascal, additional, Steininger, Philipp, additional, Zhong, Jahn, additional, Träger, Johannes, additional, Spriewald, Bernd, additional, Bock, Christoph, additional, Busch, Dirk H, additional, Bogdan, Christian, additional, Schubert, Benjamin, additional, Winkler, Thomas H, additional, Tenbusch, Matthias, additional, Schuster, Ev-Marie, additional, and Schober, Kilian, additional

Published
2024
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18. Hybrid immunity by two COVID‐19 mRNA vaccinations and one breakthrough infection provides a robust and balanced cellular immune response as basic immunity against severe acute respiratory syndrome coronavirus 2.

Author

Almanzar, Giovanni, Koosha, Kimia, Vogt, Tim, Stein, Astrid, Ziegler, Lars, Asam, Claudia, Weps, Manuela, Schwägerl, Valeria, Richter, Lorena, Hepp, Nicola, Fuchs, Andre, Wagenhäuser, Isabell, Reusch, Julia, Krone, Manuel, Geldmacher, Christof, Protzer, Ulrike, Steininger, Philipp, Überla, Klaus, Wagner, Ralf, and Liese, Johannes

Subjects
SARS-CoV-2, HUMORAL immunity, BREAKTHROUGH infections, IMMUNE response, COVID-19 vaccines, VACCINATION status
Abstract

This longitudinal prospective controlled multicenter study aimed to monitor immunity generated by three exposures caused by breakthrough infections (BTI) after COVID‐19‐vaccination considering pre‐existing cell‐mediated immunity to common‐corona‐viruses (CoV) which may impact cellular reactivity against SARS‐CoV‐2. Anti‐SARS‐CoV‐2‐spike‐IgG antibodies (anti‐S‐IgG) and cellular reactivity against Spike‐(S)‐ and nucleocapsid‐(N)‐proteins were determined in fully‐vaccinated (F) individuals who either experienced BTI (F+BTI) or had booster vaccination (F+Booster) compared to partially vaccinated (P+BTI) and unvaccinated (U) from 1 to 24 weeks post PCR‐confirmed infection. High avidity anti‐S‐IgG were found in F+BTI compared to U, the latter exhibiting increased long‐lasting pro‐inflammatory cytokines to S‐stimulation. CoV was associated with higher cellular reactivity in U, whereas no association was seen in F. The study illustrates the induction of significant S‐specific cellular responses in F+BTI building‐up basic immunity by three exposures. Only U seem to benefit from pre‐existing CoV immunity but demonstrated inflammatory immune responses compared to F+BTI who immunologically benefit from enhanced humoral and cellular immunity after BTI. This study demonstrates that individuals with hybrid immunity from COVID‐19‐vaccination and BTI acquire a stable humoral and cellular immune response that is maintained for at least 6 months. Our findings corroborate recommendations by health authorities to build on basic immunity by three S‐protein exposures. [ABSTRACT FROM AUTHOR]

Published
2024
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19. Reduction of cone‐beam CT artifacts in a robotic CBCT device using saddle trajectories with integrated infrared tracking

Author

Wei, Chengtao, primary, Albrecht, Johanna, additional, Rit, Simon, additional, Laurendeau, Matthieu, additional, Thummerer, Adrian, additional, Corradini, Stefanie, additional, Belka, Claus, additional, Steininger, Philipp, additional, Ginzinger, Felix, additional, Kurz, Christopher, additional, Riboldi, Marco, additional, and Landry, Guillaume, additional

Published
2024
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21. Investigating focal spot position drift in a mobile imaging system equipped with a monobloc‐based x‐ray generator.

Author

Messner, Ivan Michael, Keuschnigg, Peter, Stöllinger, Bernhard, Kraihamer, Mathias, Coste‐Marin, Julia, Huber, Philipp, Kellner, Daniel, Kreuzeder, Elisa Maria, Steininger, Philipp, and Deutschmann, Heinz

Subjects
IMAGING systems, CONE beam computed tomography, INTRAOPERATIVE radiotherapy, X-rays
Abstract

Background: Misalignment or double‐contouring artifacts can appear in high‐resolution 3D cone beam computed tomography (CBCT) images, potentially indicating geometric accuracy issues in the projection data. Such artifacts may go unnoticed in low‐resolution images and could be associated with changes in the focal spot (FS) position. Purpose: High‐resolution 3D‐CBCT imaging by a mobile imaging device with a large gantry clearance offers more versatility for clinical workflows in image‐guided brachytherapy (IGBT), intraoperative radiation therapy (IORT), and spinal, as well as maxillofacial surgery. However, misalignment or double‐contouring artifacts hinder workflow advancements in these domains. This paper introduces intrinsic calibration and geometrical correction methods as extensions to a well‐established technique for addressing geometrical deviations resulting from factors such as gravity or mechanical inconsistencies. These extensions cover shifts and drifts of the FS depending on FS size selection, temperature, tube current, and tube potential. The proposed methods effectively mitigate artifacts in high‐resolution CBCT images stemming from geometrical inaccuracies in projection data, without requiring additional equipment like a pinhole device. Methods: Geometrical offsets and drifts of the x‐ray tube FS were characterized on a mobile multi‐purpose imaging system, the ImagingRing‐m. A pinhole‐like experiment was simulated by adjusting the movable collimation unit to a small rectangular aperture within the FS size range. The influence of filament selection, that is, FS size, temperature, the relatively low tube currents, as well as tube potential settings have been studied on two different monobloc types sharing the same x‐ray tube insert. The Catphan 504 and an Alderson head phantom were used to assess resulting image artifacts. Results: Switching the FS size to one different from what was used for geometrical (gravitation, mechanical variations) calibration induced the most notable position changes of the x‐ray FS, resulting in double‐contouring artifacts and blurring of high‐resolution 3D‐CBCT images. Incorporating these shifts into a geometrical correction method effectively minimized these artifacts. Thermal drifts exhibited the second largest geometrical changes, comparable to FS size shifts across the thermal operating conditions of the x‐ray system. The proposed thermal drift compensation markedly reduced thermal drift effects. Tube current and potential had little impact within the range of available tube currents, eliminating the need for compensation in current applications. Conclusions: Augmenting the geometrical calibration pipeline with proposed FS drift compensations yielded significant enhancements in image quality for high‐resolution reconstructions. While compensation for thermal effects posed challenges, it proved achievable. The roles of tube current and potential were found to be negligible. [ABSTRACT FROM AUTHOR]

Published
2024
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23. Clinical and immunological benefits of full primary COVID-19 vaccination in individuals with SARS-CoV-2 breakthrough infections: a prospective cohort study in non-hospitalized adults

Author

Prelog, Martina, primary, Jeske, Samuel D., additional, Asam, Claudia, additional, Fuchs, Andre, additional, Wieser, Andreas, additional, Gall, Christine, additional, Wytopil, Monika, additional, Mueller-Schmucker, Sandra M., additional, Beileke, Stephanie, additional, Goekkaya, Mehmet, additional, Kling, Elisabeth, additional, Geldmacher, Christof, additional, Rubio-Acero, Raquel, additional, Plank, Michael, additional, Christa, Catharina, additional, Willmann, Annika, additional, Vu, Martin, additional, Einhauser, Sebastian, additional, Weps, Manuela, additional, Lampl, Benedikt M.J., additional, Almanzar, Giovanni, additional, Kousha, Kimia, additional, Schwägerl, Valeria, additional, Liebl, Bernhard, additional, Weber, Beatrix, additional, Drescher, Johannes, additional, Scheidt, Jörg, additional, Gefeller, Olaf, additional, Messmann, Helmut, additional, Protzer, Ulrike, additional, Liese, Johannes, additional, Hoelscher, Michael, additional, Wagner, Ralf, additional, Überla, Klaus, additional, Steininger, Philipp, additional, Ebigbo, Alanna, additional, Römmele, Christoph, additional, Ullrich, Maximilian, additional, Freitag, Marie, additional, Traidl-Hoffmann, Claudia, additional, Metz, Aline, additional, Holetschek, Corinna, additional, Neumann, Avidan, additional, Hoffmann, Reinhard, additional, Pruteanu, Mihail, additional, Wibmer, Thomas, additional, Rost, Susanne, additional, Müller-Schmucker, Sandra M., additional, Korn, Klaus, additional, Hastreiter, Tamara, additional, Fraedrich, Kirsten, additional, Obergfäll, Debora, additional, Neumann, Frank, additional, Kuhn, Claudia, additional, Günther, Katja, additional, Friedrich, Elke, additional, Janke, Christian, additional, Guggenbühl, Jessica, additional, Reinkemeyer, Christina, additional, Noreña, Ivan, additional, Castelletti, Noemi, additional, Acero, Raquel Rubio, additional, Ahmed, M. I.M., additional, Diepers, Paulina, additional, Eser, Tabea M., additional, Fuchs, Anna, additional, Baranov, Olga, additional, Bauer, Bernadette, additional, Wang, Danni, additional, Paunovic, Ivana, additional, Tinnefeld, Kathrin, additional, Roggendorf, Hedwig, additional, Körber, Nina, additional, Bauer, Tanja, additional, Gleich, Sabine, additional, Senninger, Antonia, additional, Carnell, George, additional, Heeney, Jonathan Luke, additional, Ebner, Antonia, additional, de Schultz, Maria José, additional, Rajes, Cedric, additional, Wafai, Aya Al, additional, Brenner, David, additional, Sicheneder, Laura, additional, Berr, Melanie, additional, Schütz, Anja, additional, Bauernfeind, Stilla, additional, Gessner, André, additional, Schmidt, Barbara, additional, Biermeier, Daniela, additional, Rothe, Ulrich, additional, Gleißner, Ute, additional, Brückner, Susanne, additional, Treml, Michaela, additional, Schedl, Holger, additional, Biermaier, Beate, additional, Achatz, Markus, additional, Hierhammer, Daniela, additional, Englhardt, Johanna, additional, Scheidl, Werner, additional, Jeyaraman, Sivaji, additional, Schutt, Barbara, additional, Prelog, Martina, additional, Bley, Julia, additional, Vogt, Tim, additional, Ziegler, Lars, additional, Stein, Astrid, additional, Förg, Franziska, additional, Löw, Johann, additional, Finkenberg, Barbara, additional, Pollak, Dennis, additional, Zamzow, Alexander, additional, Eberbach, Nicole, additional, Balkie, Lara, additional, Kretzschmann, Tanja, additional, Gehrig, Matthias, additional, Bandorf, Matthias, additional, Keck, Kilian, additional, Allmanritter, Jan, additional, Rafique, Shahid, additional, Finster, Mona, additional, Baumgart, Ingo, additional, Heumüller-Klug, Sabine, additional, Koglin, Hans-Jürgen, additional, Pfahlberg, Annette B., additional, Kaiser, Isabelle, additional, Siebenhaar, Yannic, additional, Wogenstein, Florian, additional, Reinel, Dirk, additional, Zarzitzky, Fabian, additional, Herr, Caroline, additional, Katz, Katharina, additional, Sing, Andreas, additional, and Dangel, Alexandra, additional

Published
2023
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24. Population-based study of the durability of humoral immunity after SARS-CoV-2 infection

Author

Peterhoff, David, primary, Wiegrebe, Simon, additional, Einhauser, Sebastian, additional, Patt, Arisha J., additional, Beileke, Stephanie, additional, Günther, Felix, additional, Steininger, Philipp, additional, Niller, Hans H., additional, Burkhardt, Ralph, additional, Küchenhoff, Helmut, additional, Gefeller, Olaf, additional, Überla, Klaus, additional, Heid, Iris M., additional, and Wagner, Ralf, additional

Published
2023
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27. Validation of a Parvovirus B19 NAT Assay for Screening of Umbilical Cord Blood for Allogenic Hematopoietic Stem Cell Donation.

Author

Steininger, Philipp, Korn, Klaus, Hackstein, Holger, and Strasser, Erwin F.

Subjects
*PREVENTION of infectious disease transmission, *CELL transplantation, *PARVOVIRUS diseases, *HOMOGRAFTS, *CONFIDENCE intervals, *ACADEMIC medical centers, *RESEARCH methodology, *GOVERNMENT regulation, *MEDICAL screening, *PATIENTS, *CORD blood, *CORDOCENTESIS, *MEDICAL protocols, *DESCRIPTIVE statistics, *HEMATOPOIETIC stem cell transplantation, *SENSITIVITY & specificity (Statistics), *POLYMERASE chain reaction, *DATA analysis software, *NUCLEIC acid amplification techniques, *TRANSPLANTATION of organs, tissues, etc.
Abstract

Introduction: Parvovirus B19 transmitted by umbilical cord blood (UCB) products may cause severe disease in allogenic hematopoietic stem cell transplant recipients. Thus, commercially available nucleic acid test (NAT) assays for highly sensitive detection of parvovirus B19 DNA validated for the specimen cord blood plasma (CBP) are required to avoid parvovirus B19 transmission by umbilical hematopoietic stem cell preparations. Methods: The multiplex cobas DPX NAT assay was validated for detection of parvovirus B19 DNA in CBP derived from citrate anticoagulated UCB units which have been processed by the Rubinstein method. In total, 363 retained CBP samples pretested negative for parvovirus B19 DNA were prepared for analyzing sensitivity, specificity, and interference of that NAT assay. The 3rd WHO International Standard for parvovirus B19 DNA was used for determining the 95% limit of detection (LOD95) by probit analysis. Results: The validation of the parvovirus B19 NAT assay for CBP demonstrated high sensitivity, specificity, intra- and inter-assay precision. Dilution series and replicate analyses showed a high linearity of the assay with a coefficient of determination above 0.99 and revealed a LOD95 of 17 International Units (IU)/mL (95% confidence interval, 14–44 IU/mL) for parvovirus B19 DNA in CBP samples. Conclusion: The validation of a commercially available parvovirus B19 NAT assay for the specimen CBP demonstrated a high assay performance fulfilling German guidelines and international regulations. [ABSTRACT FROM AUTHOR]

Published
2024
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28. Results of Tick-Borne Encephalitis Virus (TBEV) Diagnostics in an Endemic Area in Southern Germany, 2007 to 2022.

Author

Steininger, Philipp, Ensser, Armin, Knöll, Antje, and Korn, Klaus

Subjects
*TICK-borne encephalitis viruses, *CEREBROSPINAL fluid examination, *IMMUNOGLOBULINS, *TICK-borne encephalitis, *CEREBROSPINAL fluid, *DIAGNOSTIC use of polymerase chain reaction
Abstract

Tick-borne encephalitis virus (TBEV) is the most important tick-transmitted neurotropic flavivirus in Europe and Asia. Our analysis aimed to investigate the contribution of TBEV-specific antibody detection by serological assays and TBEV RNA detection by real-time PCR to the diagnosis of tick-borne encephalitis (TBE). We analyzed data from 3713 patients from 16 years of laboratory TBEV diagnostics in an endemic area in Southern Germany. During this period, 126 cases of TBE were diagnosed. TBEV-specific IgM ELISA tests showed a high clinical sensitivity (96.8%) and a very high clinical specificity (99.7%). In immunocompetent patients, TBE was reliably diagnosed by detection of TBEV IgM antibodies in serum. Intrathecal TBEV IgG antibody synthesis was detected in 46 of 84 (55%) cases by analysis of paired serum and cerebrospinal fluid (CSF) samples. None of the 87 immunocompetent TBE patients tested had detectable TBEV RNA in serum or CSF. In contrast, in two TBE patients without TBEV-specific antibodies, diagnosis could only be made by the detection of TBEV RNA in CSF. Both patients had previously been treated with the B cell-depleting antibody rituximab. Therefore, in patients with CNS infection and humoral immunodeficiency, it is necessary to include TBEV PCR in the diagnostic approach. [ABSTRACT FROM AUTHOR]

Published
2023
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29. Antibodies Against Glutamic Acid Decarboxylase 65 Are Locally Produced in the CSF and Arise During Affinity Maturation

Author

Biljecki, Michelle, primary, Eisenhut, Katharina, additional, Beltrán, Eduardo, additional, Winklmeier, Stephan, additional, Mader, Simone, additional, Thaller, Anna, additional, Eichhorn, Peter, additional, Steininger, Philipp, additional, Flierl-Hecht, Andrea, additional, Lewerenz, Jan, additional, Kümpfel, Tania, additional, Kerschensteiner, Martin, additional, Meinl, Edgar, additional, and Thaler, Franziska S., additional

Published
2023
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31. Propagation of SARS-CoV-2 in a Closed Cell Culture Device: Potential GMP Compatible Production Platform for Live-Attenuated Vaccine Candidates under BSL-3 Conditions?

Author

Klessing, Stephan, primary, Peter, Antonia Sophia, additional, Fraedrich, Kirsten, additional, Wagner, Jannik T., additional, Kummer, Mirko, additional, Deutschmann, Janina, additional, Steininger, Philipp, additional, Steibl, Hans-Dieter, additional, and Überla, Klaus, additional

Published
2023
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32. Class switch toward noninflammatory, spike-specific IgG4 antibodies after repeated SARS-CoV-2 mRNA vaccination

Author

Irrgang, Pascal, primary, Gerling, Juliane, additional, Kocher, Katharina, additional, Lapuente, Dennis, additional, Steininger, Philipp, additional, Habenicht, Katharina, additional, Wytopil, Monika, additional, Beileke, Stephanie, additional, Schäfer, Simon, additional, Zhong, Jahn, additional, Ssebyatika, George, additional, Krey, Thomas, additional, Falcone, Valeria, additional, Schülein, Christine, additional, Peter, Antonia Sophia, additional, Nganou-Makamdop, Krystelle, additional, Hengel, Hartmut, additional, Held, Jürgen, additional, Bogdan, Christian, additional, Überla, Klaus, additional, Schober, Kilian, additional, Winkler, Thomas H., additional, and Tenbusch, Matthias, additional

Published
2023
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33. Fatal Puumala Hantavirus Infection in a Patient with Common Variable Immunodeficiency (CVID)

Author

Steininger, Philipp, primary, Herbst, Larissa, additional, Bihlmaier, Karl, additional, Willam, Carsten, additional, Körper, Sixten, additional, Schrezenmeier, Hubert, additional, Klüter, Harald, additional, Pfister, Frederick, additional, Amann, Kerstin, additional, Weiss, Sabrina, additional, Krüger, Detlev H., additional, Zimmermann, Robert, additional, Korn, Klaus, additional, Hofmann, Jörg, additional, and Harrer, Thomas, additional

Published
2023
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35. Higher Infection Risk among Health Care Workers and Lower Risk among Smokers Persistent across SARS-CoV-2 Waves—Longitudinal Results from the Population-Based TiKoCo Seroprevalence Study

Author

Günther, Felix, primary, Einhauser, Sebastian, additional, Peterhoff, David, additional, Wiegrebe, Simon, additional, Niller, Hans Helmut, additional, Beileke, Stephanie, additional, Steininger, Philipp, additional, Burkhardt, Ralph, additional, Küchenhoff, Helmut, additional, Gefeller, Olaf, additional, Überla, Klaus, additional, Heid, Iris M., additional, and Wagner, Ralf, additional

Published
2022
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36. Enhanced Spike-specific, but attenuated Nucleocapsid-specific T cell responses upon SARS-CoV-2 breakthrough versus non-breakthrough infections

Author

Ahmed, Mohamed Ibraheem Mahmoud, primary, Diepers, Paulina, additional, Janke, Christian, additional, Plank, Michael, additional, Eser, Tabea M., additional, Rubio-Acero, Raquel, additional, Fuchs, Anna, additional, Baranov, Olga, additional, Castelletti, Noemi, additional, Kroidl, Inge, additional, Olbrich, Laura, additional, Bauer, Bernadette, additional, Wang, Danni, additional, Prelog, Martina, additional, Liese, Johannes G., additional, Reinkemeyer, Christina, additional, Hoelscher, Michael, additional, Steininger, Philipp, additional, Überla, Klaus, additional, Wieser, Andreas, additional, and Geldmacher, Christof, additional

Published
2022
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39. Additional file 3 of Reactogenicity and safety of COVID-19 primary immunisation and booster vaccination regimens: a comparative observational cohort study

Author

Warkentin, Lisette, Werner, Felix, Zeschick, Nikoletta, Kühlein, Thomas, Steininger, Philipp, Überla, Klaus, Kaiser, Isabelle, Sebastião, Maria, and Hueber, Susann

Abstract

Additional file 3:Table S1. Descriptive results of the short-term surveys. Table S2. Influence of SARS-CoV-2 infection on reporting outcomes. Logistic regression.

Published
2023
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40. CoVaKo: Corona vaccine consortium - an online observational study to evaluate reactogenicity after various vaccines

Author

Hueber, Susann, Warkentin, Lisette, Lippert, Nikoletta, Sebastiao, Maria, Werner, Felix, Nürnberger, Carolin, Gall, Christine, Kaiser, Isabelle, Steininger, Philipp, Überla, Klaus, and Kühlein, Thomas

Subjects
ddc: 610, Medicine and health
Abstract

Background and status of (inter)national research: The efficacy and safety of COVID-19 vaccines have been demonstrated in large randomized controlled trials. In addition, observational studies provide further important insights into the safety and efficacy of the vaccines under real-life conditions. [for full text, please go to the a.m. URL]

Published
2022

41. Dynamics of humoral and cellular immune responses after homologous and heterologous SARS-CoV-2 vaccination with ChAdOx1 nCoV-19 and BNT162b2

Author

Vogel, Emanuel, primary, Kocher, Katharina, additional, Priller, Alina, additional, Cheng, Cho-Chin, additional, Steininger, Philipp, additional, Liao, Bo-Hung, additional, Körber, Nina, additional, Willmann, Annika, additional, Irrgang, Pascal, additional, Held, Jürgen, additional, Moosmann, Carolin, additional, Schmidt, Viviane, additional, Beileke, Stephanie, additional, Wytopil, Monika, additional, Heringer, Sarah, additional, Bauer, Tanja, additional, Brockhoff, Ronja, additional, Jeske, Samuel, additional, Mijocevic, Hrvoje, additional, Christa, Catharina, additional, Salmanton-García, Jon, additional, Tinnefeld, Kathrin, additional, Bogdan, Christian, additional, Yazici, Sarah, additional, Knolle, Percy, additional, Cornely, Oliver A., additional, Überla, Klaus, additional, Protzer, Ulrike, additional, Schober, Kilian, additional, and Tenbusch, Matthias, additional

Published
2022
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44. Class switch towards non-inflammatory IgG isotypes after repeated SARS-CoV-2 mRNA vaccination

Author

Irrgang, Pascal, primary, Gerling, Juliane, additional, Kocher, Katharina, additional, Lapuente, Dennis, additional, Steininger, Philipp, additional, Wytopil, Monika, additional, Schäfer, Simon, additional, Habenicht, Katharina, additional, Zhong, Jahn, additional, Ssebyatika, George, additional, Krey, Thomas, additional, Falcone, Valeria, additional, Schülein, Christine, additional, Peter, Antonia Sophia, additional, Nganou-Makamdop, Krystelle, additional, Hengel, Hartmut, additional, Held, Jürgen, additional, Bogdan, Christian, additional, Überla, Klaus, additional, Schober, Kilian, additional, Winkler, Thomas H., additional, and Tenbusch, Matthias, additional

Published
2022
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45. Time Trend in SARS-CoV-2 Seropositivity, Surveillance Detection- and Infection Fatality Ratio until Spring 2021 in the Tirschenreuth County-Results from a Population-Based Longitudinal Study in Germany

Author

Einhauser, Sebastian, Peterhoff, David, Beileke, Stephanie, Günther, Felix, Niller, Hans-Helmut, Steininger, Philipp, Knöll, Antje, Korn, Klaus, Berr, Melanie, Schütz, Anja, Wiegrebe, Simon, Stark, Klaus J., Gessner, André, Burkhardt, Ralph, Kabesch, Michael, Schedl, Holger, Küchenhoff, Helmut, Pfahlberg, Annette B., Heid, Iris M., Gefeller, Olaf, Überla, Klaus, Wagner, Ralf, Einhauser, Sebastian, Peterhoff, David, Beileke, Stephanie, Günther, Felix, Niller, Hans-Helmut, Steininger, Philipp, Knöll, Antje, Korn, Klaus, Berr, Melanie, Schütz, Anja, Wiegrebe, Simon, Stark, Klaus J., Gessner, André, Burkhardt, Ralph, Kabesch, Michael, Schedl, Holger, Küchenhoff, Helmut, Pfahlberg, Annette B., Heid, Iris M., Gefeller, Olaf, Überla, Klaus, and Wagner, Ralf

Abstract

Herein, we provide results from a prospective population-based longitudinal follow-up (FU) SARS-CoV-2 serosurveillance study in Tirschenreuth, the county which was hit hardest in Germany in spring 2020 and early 2021. Of 4203 individuals aged 14 years or older enrolled at baseline (BL, June 2020), 3546 participated at FU1 (November 2020) and 3391 at FU2 (April 2021). Key metrics comprising standardized seroprevalence, surveillance detection ratio (SDR), infection fatality ratio (IFR) and success of the vaccination campaign were derived using the Roche N- and S-Elecsys anti-SARS-CoV-2 test together with a self-administered questionnaire. N-seropositivity at BL was 9.2% (1st wave). While we observed a low new seropositivity between BL and FU1 (0.9%), the combined 2nd and 3rd wave accounted for 6.1% new N-seropositives between FU1 and FU2 (ever seropositives at FU2: 15.4%). The SDR decreased from 5.4 (BL) to 1.1 (FU2) highlighting the success of massively increased testing in the population. The IFR based on a combination of serology and registration data resulted in 3.3% between November 2020 and April 2021 compared to 2.3% until June 2020. Although IFRs were consistently higher at FU2 compared to BL across age-groups, highest among individuals aged 70+ (18.3% versus 10.7%, respectively), observed differences were within statistical uncertainty bounds. While municipalities with senior care homes showed a higher IFR at BL (3.0% with senior care home vs. 0.7% w/o), this effect diminished at FU2 (3.4% vs. 2.9%). In April 2021 (FU2), vaccination rate in the elderly was high (>77.4%, age-group 80+).

Published
2022
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46. Comparative Immunogenicity of COVID-19 Vaccines in a Population-Based Cohort Study with SARS-CoV-2-Infected and Uninfected Participants

Author

Peterhoff, David, Einhauser, Sebastian, Beileke, Stephanie, Niller, Hans-Helmut, Günther, Felix, Schachtner, Michael, Asbach, Benedikt, Steininger, Philipp, Tenbusch, Matthias, Peter, Antonia S., Gessner, Andre, Burkhardt, Ralph, Heid, Iris M., Wagner, Ralf, Überla, Klaus, Peterhoff, David, Einhauser, Sebastian, Beileke, Stephanie, Niller, Hans-Helmut, Günther, Felix, Schachtner, Michael, Asbach, Benedikt, Steininger, Philipp, Tenbusch, Matthias, Peter, Antonia S., Gessner, Andre, Burkhardt, Ralph, Heid, Iris M., Wagner, Ralf, and Überla, Klaus

Abstract

To assess vaccine immunogenicity in non-infected and previously infected individuals in a real-world scenario, SARS-CoV-2 antibody responses were determined during follow-up 2 (April 2021) of the population-based Tirschenreuth COVID-19 cohort study comprising 3378 inhabitants of the Tirschenreuth county aged 14 years or older. Seronegative participants vaccinated once with Vaxzevria, Comirnaty, or Spikevax had median neutralizing antibody titers ranging from ID50 = 25 to 75. Individuals with two immunizations with Comirnaty or Spikevax had higher median ID50s (of 253 and 554, respectively). Regression analysis indicated that both increased age and increased time since vaccination independently decreased RBD binding and neutralizing antibody levels. Unvaccinated participants with detectable N-antibodies at baseline (June 2020) revealed a median ID50 of 72 at the April 2021 follow-up. Previously infected participants that received one dose of Vaxzevria or Comirnaty had median ID50 to 929 and 2502, respectively. Individuals with a second dose of Comirnaty given in a three-week interval after the first dose did not have higher median antibody levels than individuals with one dose. Prior infection also primed for high systemic IgA levels in response to one dose of Comirnaty that exceeded IgA levels observed after two doses of Comirnaty in previously uninfected participants. Neutralizing antibody levels targeting the spike protein of Beta and Delta variants were diminished compared to the wild type in vaccinated and infected participants.

Published
2022
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47. Higher Infection Risk among Health Care Workers and Lower Risk among Smokers Persistent across SARS-CoV-2 Waves - Longitudinal Results from the Population-Based TiKoCo Seroprevalence Study

Author

Günther, Felix, Einhauser, Sebastian, Peterhoff, David, Wiegrebe, Simon, Niller, Hans Helmut, Beileke, Stephanie, Steininger, Philipp, Burkhardt, Ralph, Küchenhoff, Helmut, Gefeller, Olaf, Überla, Klaus, Heid, Iris M., Wagner, Ralf, Günther, Felix, Einhauser, Sebastian, Peterhoff, David, Wiegrebe, Simon, Niller, Hans Helmut, Beileke, Stephanie, Steininger, Philipp, Burkhardt, Ralph, Küchenhoff, Helmut, Gefeller, Olaf, Überla, Klaus, Heid, Iris M., and Wagner, Ralf

Abstract

SARS-CoV-2 seroprevalence was reported as substantially increased in medical personnel and decreased in smokers after the first wave in spring 2020, including in our population-based Tirschenreuth Study (TiKoCo). However, it is unclear whether these associations were limited to the early pandemic and whether the decrease in smokers was due to reduced infection or antibody response. We evaluated the association of occupation and smoking with period-specific seropositivity: for the first wave until July 2020 (baseline, BL), the low infection period in summer (follow-up 1, FU1, November 2020), and the second/third wave (FU2, April 2021). We measured binding antibodies directed to SARS-CoV-2 nucleoprotein (N), viral spike protein (S), and neutralizing antibodies at BL, FU1, and FU2. Previous infection, vaccination, smoking, and occupation were assessed by questionnaires. The 4181 participants (3513/3374 at FU1/FU2) included 6.5% medical personnel and 20.4% current smokers. At all three timepoints, new seropositivity was higher in medical personnel with ORs = 1.99 (95%-CI = 1.36–2.93), 1.41 (0.29–6.80), and 3.17 (1.92–5.24) at BL, FU1, and FU2, respectively, and nearly halved among current smokers with ORs = 0.47 (95%-CI = 0.33–0.66), 0.40 (0.09–1.81), and 0.56 (0.33–0.94). Current smokers compared to never-smokers had similar antibody levels after infection or vaccination and reduced odds of a positive SARS-CoV-2 result among tested. Our data suggest that decreased seroprevalence among smokers results from fewer infections rather than reduced antibody response. The persistently higher infection risk of medical staff across infection waves, despite improved means of protection over time, underscores the burden for health care personnel.

Published
2022
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48. Dynamics of humoral and cellular immune responses after homologous and heterologous SARS-CoV-2 vaccination with ChAdOx1 nCoV-19 and BNT162b2

Author

Vogel, Emanuel, Kocher, Katharina, Priller, Alina, Cheng, Cho-Chin, Steininger, Philipp, Liao, Bo-Hung, Korber, Nina, Willmann, Annika, Irrgang, Pascal, Held, Juergen, Moosmann, Carolin, Schmidt, Viviane, Beileke, Stephanie, Wytopil, Monika, Heringer, Sarah, Bauer, Tanja, Brockhoff, Ronja, Jeske, Samuel, Mijocevic, Hrvoje, Christa, Catharina, Salmanton-Garcia, Jon, Tinnefeld, Kathrin, Bogdan, Christian, Yazici, Sarah, Knolle, Percy, Cornely, Oliver A., Ueberla, Klaus, Protzer, Ulrike, Schober, Kilian, Tenbusch, Matthias, Vogel, Emanuel, Kocher, Katharina, Priller, Alina, Cheng, Cho-Chin, Steininger, Philipp, Liao, Bo-Hung, Korber, Nina, Willmann, Annika, Irrgang, Pascal, Held, Juergen, Moosmann, Carolin, Schmidt, Viviane, Beileke, Stephanie, Wytopil, Monika, Heringer, Sarah, Bauer, Tanja, Brockhoff, Ronja, Jeske, Samuel, Mijocevic, Hrvoje, Christa, Catharina, Salmanton-Garcia, Jon, Tinnefeld, Kathrin, Bogdan, Christian, Yazici, Sarah, Knolle, Percy, Cornely, Oliver A., Ueberla, Klaus, Protzer, Ulrike, Schober, Kilian, and Tenbusch, Matthias

Abstract

Background Vaccines are an important means to overcome the SARS-CoV-2 pandemic. They induce specific anti-body and T-cell responses but it remains open how well vaccine-induced immunity is preserved over time following homologous and heterologous immunization regimens. Here, we compared the dynamics of humoral and cellular immune responses up to 180 days after homologous or heterologous vaccination with either ChAdOx1-nCoV-19 (ChAd) or BNT162b2 (BNT) or both.Methods Various tests were used to determine the humoral and cellular immune response. To quantify the antibody levels, we used the surrogate neutralization (sVNT) assay from YHLO, which we augmented with pseudo-and real virus neutralization tests (pVNT and rVNT). Antibody avidity was measured by a modified ELISA. To determine cel-lular reactivity, we used an IFN-g Elispot, IFN-g/IL Flurospot, and intracellular cytokine staining.Findings Antibody responses significantly waned after vaccination, irrespective of the regimen. The capacity to neu-tralize SARS-CoV-2 -including variants of concern such as Delta or Omicron -was superior after heterologous compared to homologous BNT vaccination, both of which resulted in longer-lasting humoral immunity than homol-ogous ChAd immunization. All vaccination regimens induced stable, polyfunctional T-cell responses. Interpretation These findings demonstrate that heterologous vaccination with ChAd and BNT is a potent alternative to induce humoral and cellular immune protection in comparison to the homologous vaccination regimens.Copyright (c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Published
2022

50. First Clinical Release of an Online, Adaptive, Aperture-Based Image-Guided Radiotherapy Strategy in Intensity-Modulated Radiotherapy to Correct for Inter- and Intrafractional Rotations of the Prostate

Author

Deutschmann, Heinz, Kametriser, Gerhard, Steininger, Philipp, Scherer, Philipp, Schöller, Helmut, Gaisberger, Christoph, Mooslechner, Michaela, Mitterlechner, Bernhard, Weichenberger, Harald, Fastner, Gert, Wurstbauer, Karl, Jeschke, Stephan, Forstner, Rosemarie, and Sedlmayer, Felix

Published
2012
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