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2. Fading SARS-CoV-2 humoral VOC cross-reactivity and sustained cellular immunity in convalescent children and adolescents

Author

Paniskaki, Krystallenia, Goretzki, Sarah, Anft, Moritz, Konik, Margarethe J., Lechtenberg, Klara, Vogl, Melanie, Meister, Toni L., Pfaender, Stephanie, Zettler, Markus, Jäger, Jasmin, Dolff, Sebastian, Westhoff, Timm H., Rohn, Hana, Felderhoff-Mueser, Ursula, Stervbo, Ulrik, Witzke, Oliver, Dohna-schwake, Christian, and Babel, Nina

Published
2023
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3. Copper and silver thin film systems display differences in antiviral and antibacterial properties -- implications for the prevention of SARS-CoV-2 infections

Author

Meister, Toni Luise, Fortmann, Jill, Breisch, Marina, Sengstock, Christina, Steinmann, Eike, Koeller, Manfred, Pfaender, Stephanie, and Ludwig, Alfred

Subjects
Physics - Medical Physics, Physics - Biological Physics
Abstract

The current Coronavirus Disease 19 (COVID-19) pandemic has exemplified the need for simple and efficient prevention strategies that can be rapidly implemented to mitigate infection risks. Various surfaces have a long history of antimicrobial properties and are well described for the prevention of bacterial infections. However, their effect on many viruses has not been studied in depth. In the context of COVID-19, several surfaces, including copper (Cu) and silver (Ag) coatings have been described as efficient antiviral measures that can easily be implemented to slow viral transmission. In this study, we detected antiviral properties against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) on surfaces, which were coated with Cu by magnetron sputtering. However, no effect of Ag on viral titers was observed, in clear contrast to its well-known antibacterial properties. Further enhancement of Ag ion release kinetics based on an electrochemical sacrificial anode mechanism did not increase antiviral activity. These results clearly demonstrate that Cu and Ag thin film systems display significant differences in antiviral and antibacterial properties which need to be considered upon implementation.

Published
2021

4. Exploring the relationship between HCMV serostatus and outcomes in COVID-19 sepsis

Author

Ziehe, Dominik, primary, Wolf, Alexander, additional, Rahmel, Tim, additional, Nowak, Hartmuth, additional, Haberl, Helge, additional, Bergmann, Lars, additional, Rump, Katharina, additional, Dyck, Birte, additional, Palmowski, Lars, additional, Marko, Britta, additional, Witowski, Andrea, additional, Willemsen, Katrin Maria, additional, Pfaender, Stephanie, additional, Eisenacher, Martin, additional, Anft, Moritz, additional, Babel, Nina, additional, Bracht, Thilo, additional, Sitek, Barbara, additional, Bayer, Malte, additional, Zarbock, Alexander, additional, von Groote, Thilo, additional, Putensen, Christian, additional, Ehrentraut, Stefan Felix, additional, Weisheit, Christina, additional, Adamzik, Michael, additional, Unterberg, Matthias, additional, and Koos, Björn, additional

Published
2024
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5. Inhibitors of dihydroorotate dehydrogenase cooperate with molnupiravir and N4-hydroxycytidine to suppress SARS-CoV-2 replication

Author

Stegmann, Kim M., Dickmanns, Antje, Heinen, Natalie, Blaurock, Claudia, Karrasch, Tim, Breithaupt, Angele, Klopfleisch, Robert, Uhlig, Nadja, Eberlein, Valentina, Issmail, Leila, Herrmann, Simon T., Schreieck, Amelie, Peelen, Evelyn, Kohlhof, Hella, Sadeghi, Balal, Riek, Alexander, Speakman, John R., Groß, Uwe, Görlich, Dirk, Vitt, Daniel, Müller, Thorsten, Grunwald, Thomas, Pfaender, Stephanie, Balkema-Buschmann, Anne, and Dobbelstein, Matthias

Published
2022
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8. The triglyceride-synthesizing enzyme diacylglycerol acyltransferase 2 modulates the formation of the hepatitis C virus replication organelle.

Author

Reichert, Isabelle, Lee, Ji-Young, Weber, Laura, Fuh, Marceline M., Schlaeger, Lina, Rößler, Stefanie, Kinast, Volker, Schlienkamp, Sarah, Conradi, Janina, Vondran, Florian W. R., Pfaender, Stephanie, Scaturro, Pietro, Steinmann, Eike, Bartenschlager, Ralf, Pietschmann, Thomas, Heeren, Joerg, Lauber, Chris, and Vieyres, Gabrielle

Subjects
HEPATITIS C virus, UNSATURATED fatty acids, INTRACELLULAR membranes, ENDOPLASMIC reticulum, HEPATITIS C
Abstract

The replication organelle of hepatitis C virus (HCV), called membranous web, is derived from the endoplasmic reticulum (ER) and mainly comprises double membrane vesicles (DMVs) that concentrate the viral replication complexes. It also tightly associates with lipid droplets (LDs), which are essential for virion morphogenesis. In particular acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), a rate-limiting enzyme in triglyceride synthesis, promotes early steps of virus assembly. The close proximity between ER membranes, DMVs and LDs therefore permits the efficient coordination of the HCV replication cycle. Here, we demonstrate that exaggerated LD accumulation due to the excessive expression of the DGAT1 isozyme, DGAT2, dramatically impairs the formation of the HCV membranous web. This effect depended on the enzymatic activity and ER association of DGAT2, whereas the mere LD accumulation was not sufficient to hamper HCV RNA replication. Our lipidomics data indicate that both HCV infection and DGAT2 overexpression induced membrane lipid biogenesis and markedly increased phospholipids with long chain polyunsaturated fatty acids, suggesting a dual use of these lipids and their possible competition for LD and DMV biogenesis. On the other hand, overexpression of DGAT2 depleted specific phospholipids, particularly oleyl fatty acyl chain-containing phosphatidylcholines, which, in contrast, are increased in HCV-infected cells and likely essential for viral infection. In conclusion, our results indicate that lipid exchanges occurring during LD biogenesis regulate the composition of intracellular membranes and thereby affect the formation of the HCV replication organelle. The potent antiviral effect observed in our DGAT2 overexpression system unveils lipid flux that may be relevant in the context of steatohepatitis, a hallmark of HCV infection, but also in physiological conditions, locally in specific subdomains of the ER membrane. Thus, LD formation mediated by DGAT1 and DGAT2 might participate in the spatial compartmentalization of HCV replication and assembly factories within the membranous web. Author summary: Lipid droplets are fat storage organelles with an increasingly recognized importance for the infectious cycle of multiple pathogens. In particular, they support hepatitis C virion morphogenesis and the formation of the picornaviral replication organelle. Unexpectedly, we observed that exaggerated lipid droplet biogenesis, due to an excessive expression of the triglyceride forming enzyme DGAT2, is deleterious to hepatitis C virus replication. More precisely, the formation and maintenance of the viral replication organelle was impeded. Exaggerated lipid droplet biogenesis induced by DGAT2 also profoundly altered the cell lipidome, with strong accumulation of neutral lipids and changes in the membrane lipid composition. Our results support a model where lipid flux occurring during lipid droplet biogenesis regulates the composition of the endoplasmic reticulum membranes, where lipid droplets are formed, and thereby affect the capacity of hepatitis C virus to remodel these membranes into its replication organelle. Since DGAT1 and its triglyceride synthesis were previously reported to contribute to virus assembly, this also implies that lipid droplet biogenesis driven by DGAT1 and DGAT2 but also membrane contact sites between endoplasmic reticulum and lipid droplets might locally restrict and determine the formation of hepatitis C virus replication and assembly factories. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Robust T Cell Response Toward Spike, Membrane, and Nucleocapsid SARS-CoV-2 Proteins Is Not Associated with Recovery in Critical COVID-19 Patients

Author

Thieme, Constantin J., Anft, Moritz, Paniskaki, Krystallenia, Blazquez-Navarro, Arturo, Doevelaar, Adrian, Seibert, Felix S., Hoelzer, Bodo, Konik, Margarethe Justine, Berger, Marc Moritz, Brenner, Thorsten, Tempfer, Clemens, Watzl, Carsten, Meister, Toni L., Pfaender, Stephanie, Steinmann, Eike, Dolff, Sebastian, Dittmer, Ulf, Westhoff, Timm H., Witzke, Oliver, Stervbo, Ulrik, Roch, Toralf, and Babel, Nina

Published
2020
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11. Inactivation of Severe Acute Respiratory Syndrome Coronavirus 2 by WHO-Recommended Hand Rub Formulations and Alcohols

Author

Kratzel, Annika, Todt, Daniel, Vkovski, Philip, Steiner, Silvio, Gultom, Mitra, Thao, Tran Thi Nhu, Ebert, Nadine, Holwerda, Melle, Steinmann, Jorg, Niemeyer, Daniela, Dijkman, Ronald, Kampf, Gunter, Drosten, Christian, Steinmann, Eike, Thiel, Volker, and Pfaender, Stephanie

Subjects
Severe acute respiratory syndrome -- Health aspects, Alcohols -- Health aspects, Coronaviruses -- Health aspects, COVID-19 -- Health aspects, Health
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third highly pathogenic human coronavirus to cross the species barrier into the human population during the past 20 years (2-3). SARS-CoV-2 [...]

Published
2020
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12. Rapid reconstruction of SARS-CoV-2 using a synthetic genomics platform

Author

Thi Nhu Thao, Tran, Labroussaa, Fabien, Ebert, Nadine, V’kovski, Philip, Stalder, Hanspeter, Portmann, Jasmine, Kelly, Jenna, Steiner, Silvio, Holwerda, Melle, Kratzel, Annika, Gultom, Mitra, Schmied, Kimberly, Laloli, Laura, Hüsser, Linda, Wider, Manon, Pfaender, Stephanie, Hirt, Dagny, Cippà, Valentina, Crespo-Pomar, Silvia, Schröder, Simon, Muth, Doreen, Niemeyer, Daniela, Corman, Victor M., Müller, Marcel A., Drosten, Christian, Dijkman, Ronald, Jores, Joerg, and Thiel, Volker

Published
2020
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13. Immune protection against reinfection with nonprimate hepacivirus

Author

Pfaender, Stephanie, Walter, Stephanie, Grabski, Elena, Todt, Daniel, Bruening, Janina, Romero-Brey, Inés, Gather, Theresa, Brown, Richard J. P., Hahn, Kerstin, Puff, Christina, Pfankuche, Vanessa M., Hansmann, Florian, Postel, Alexander, Becher, Paul, Thiel, Volker, Kalinke, Ulrich, Wagner, Bettina, Bartenschlager, Ralf, Baumgärtner, Wolfgang, Feige, Karsten, Pietschmann, Thomas, Cavalleri, Jessika M. V., and Steinmann, Eike

Published
2017

14. Significant Fade of Neutralizing Antibodies and Stable Cellular Immunity in 4 Times COVID-19 Vaccinated Noninfected Compared to COVID-19 Convalescent and 3 Times Vaccinated Hemodialysis Patients

Author

Anft, Moritz, primary, Skrzypczyk, Sarah, additional, Frahnert, Michael, additional, Fricke, Lutz, additional, Zapka, Jan, additional, Kühn, Daniel, additional, Koos, Björn, additional, Adamzik, Michael, additional, Pfaender, Stephanie, additional, Stervbo, Ulrik, additional, Westhoff, Timm H., additional, and Babel, Nina, additional

Published
2023
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16. Low avidity circulating SARS-CoV-2 reactive CD8+ T cells with proinflammatory TEMRA phenotype are associated with post-acute sequelae of COVID-19

Author

Paniskaki, Krystallenia, Konik, Margarethe J., Anft, Moritz, Heidecke, Harald, Meister, Toni L., Pfaender, Stephanie, Krawczyk, Adalbert, Zettler, Markus, Jäger, Jasmin, Gaeckler, Anja, Dolff, Sebastian, Westhoff, Timm H., Rohn, Hana, Stervbo, Ulrik, Scheibenbogen, Carmen, Witzke, Oliver, and Babel, Nina

Subjects
Microbiology (medical), Medizin, Microbiology
Abstract

The role of adaptive SARS-CoV-2 specific immunity in post-acute sequelae of COVID-19 (PASC) is not well explored, although a growing population of convalescent COVID-19 patients with manifestation of PASC is observed. We analyzed the SARS-CoV-2-specific immune response, via pseudovirus neutralizing assay and multiparametric flow cytometry in 40 post-acute sequelae of COVID-19 patients with non-specific PASC manifestation and 15 COVID-19 convalescent healthy donors. Although frequencies of SARS-CoV-2-reactive CD4+ T cells were similar between the studied cohorts, a stronger SARS-CoV-2 reactive CD8+ T cell response, characterized by IFNγ production and predominant TEMRA phenotype but low functional TCR avidity was detected in PASC patients compared to controls. Of interest, high avidity SARS-CoV-2-reactive CD4+ and CD8+ T cells were comparable between the groups demonstrating sufficient cellular antiviral response in PASC. In line with the cellular immunity, neutralizing capacity in PASC patients was not inferior compared to controls. In conclusion, our data suggest that PASC may be driven by an inflammatory response triggered by an expanded population of low avidity SARS-CoV-2 reactive pro-inflammatory CD8+ T cells. These pro-inflammatory T cells with TEMRA phenotype are known to be activated by a low or even without TCR stimulation and lead to a tissue damage. Further studies including animal models are required for a better understanding of underlying immunopathogensis. Summary: A CD8+ driven persistent inflammatory response triggered by SARS-CoV-2 may be responsible for the observed sequelae in PASC patients. CA extern

Published
2023

17. Impact of SARS-CoV-2 vaccination on systemic immune responses in people living with HIV

Author

Bessen, Clara, primary, Plaza-Sirvent, Carlos, additional, Simsek, Agit, additional, Bhat, Jaydeep, additional, Marheinecke, Corinna, additional, Urlaub, Doris, additional, Bonowitz, Petra, additional, Busse, Sandra, additional, Schumann, Sabrina, additional, Blanco, Elena Vidal, additional, Skaletz-Rorowski, Adriane, additional, Brockmeyer, Norbert H., additional, Overheu, Oliver, additional, Reinacher-Schick, Anke, additional, Faissner, Simon, additional, Watzl, Carsten, additional, Pfaender, Stephanie, additional, Potthoff, Anja, additional, and Schmitz, Ingo, additional

Published
2022
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18. Superior humoral immunity in vaccinated SARS-CoV-2 convalescence as compared to SARS-COV-2 infection or vaccination

Author

Paniskaki, Krystallenia, primary, Konik, Margarethe J., additional, Anft, Moritz, additional, Meister, Toni L., additional, Marheinecke, Corinna, additional, Pfaender, Stephanie, additional, Jäger, Jasmin, additional, Krawczyk, Adalbert, additional, Zettler, Markus, additional, Dolff, Sebastian, additional, Westhoff, Timm H., additional, Rohn, Hana, additional, Stervbo, Ulrik, additional, Witzke, Oliver, additional, and Babel, Nina, additional

Published
2022
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19. SARS-CoV-2 neutralizing camelid heavy-chain-only antibodies as powerful tools for diagnostic and therapeutic applications

Author

Schlör, Anja, primary, Hirschberg, Stefan, additional, Amor, Ghada Ben, additional, Meister, Toni Luise, additional, Arora, Prerna, additional, Pöhlmann, Stefan, additional, Hoffmann, Markus, additional, Pfaender, Stephanie, additional, Eddin, Omar Kamal, additional, Kamhieh-Milz, Julian, additional, and Hanack, Katja, additional

Published
2022
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21. Different humoral but similar cellular responses of patients with autoimmune inflammatory rheumatic diseases under disease-modifying antirheumatic drugs after COVID-19 vaccination

Author

Andreica, Ioana, primary, Blazquez-Navarro, Arturo, additional, Sokolar, Jan, additional, Anft, Moritz, additional, Kiltz, Uta, additional, Pfaender, Stephanie, additional, Vidal Blanco, Elena, additional, Westhoff, Timm, additional, Babel, Nina, additional, Stervbo, Ulrik, additional, and Baraliakos, Xenofon, additional

Published
2022
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22. Immune response in ofatumumab treated multiple sclerosis patients after SARS-CoV-2 vaccination

Author

Faissner, Simon, primary, Heitmann, Neele, additional, Plaza-Sirvent, Carlos, additional, Trendelenburg, Paulina, additional, Ceylan, Ulas, additional, Motte, Jeremias, additional, Bessen, Clara, additional, Urlaub, Doris, additional, Watzl, Carsten, additional, Overheu, Oliver, additional, Reinacher-Schick, Anke, additional, Hellwig, Kerstin, additional, Pfaender, Stephanie, additional, Schmitz, Ingo, additional, and Gold, Ralf, additional

Published
2022
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23. Vaccine-associated enhanced respiratory pathology in COVID-19 hamsters after TH2-biased immunization

Author

Ebenig, Aileen, primary, Muraleedharan, Samada, additional, Kazmierski, Julia, additional, Todt, Daniel, additional, Auste, Arne, additional, Anzaghe, Martina, additional, Gömer, André, additional, Postmus, Dylan, additional, Gogesch, Patricia, additional, Niles, Marc, additional, Plesker, Roland, additional, Miskey, Csaba, additional, Gellhorn Serra, Michelle, additional, Breithaupt, Angele, additional, Hörner, Cindy, additional, Kruip, Carina, additional, Ehmann, Rosina, additional, Ivics, Zoltan, additional, Waibler, Zoe, additional, Pfaender, Stephanie, additional, Wyler, Emanuel, additional, Landthaler, Markus, additional, Kupke, Alexandra, additional, Nouailles, Geraldine, additional, Goffinet, Christine, additional, Brown, Richard J.P., additional, and Mühlebach, Michael D., additional

Published
2022
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25. A Vector-Based Vaccine Dose After 3 Doses of mRNA-Based COVID-19 Vaccination Does Not Substantially Improve Humoral SARS-CoV-2 Immunity in Renal Transplant Recipients

Author

Roch, Toralf, primary, Rohn, Benjamin, additional, Blazquez-Navarro, Arturo, additional, Meister, Toni L., additional, Blanco, Elena Vidal, additional, Paniskaki, Krystallenia, additional, Wellenkötter, Jacqueline, additional, Zgoura, Panagiota, additional, Giglio, Tina, additional, Pfaender, Stephanie, additional, Stervbo, Ulrik, additional, Viebahn, Richard, additional, Cinkilic, Okan, additional, Westhoff, Timm H., additional, and Babel, Nina, additional

Published
2022
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26. Intra-host analysis of hepaciviral glycoprotein evolution reveals signatures associated with viral persistence and clearance

Author

Gömer, André, Todt, Daniel, Steinmann, Eike, Wedemeyer, Heiner, Pietschmann, Thomas, Cavalleri, Jessika M. V., Bock, C-Thomas, Seitz, Stefan, Orton, Richard, Reuter, Gábor, Deterding, Katja, Pfaender, Stephanie, and Brown, Richard J. P.

Subjects
equine hepacivirus, Hepatitis C virus, intra-host evolution, Hepatitis-C Virus, Hypervariable Region 1, T-Cell Responses, Sequence Stability, Equine Hepacivirus, Antiviral Therapy, Infection, Transmission, Replication, Selection, ddc:610, 610 Medizin und Gesundheit, glycoprotein variability, hypervariable region
Abstract

Even 30 years after the discovery of the hepatitis C virus (HCV) in humans there is still no vaccine available. Reasons for this include the high mutation rate of HCV, which allows the virus to escape immune recognition and the absence of an immunocompetent animal model for vaccine development. Phylogenetically distinct hepaciviruses (genus \(\it Hepacivirus\), family \(\it Flaviviridae\)) have been isolated from diverse species, each with a narrow host range: the equine hepacivirus (EqHV) is the closest known relative of HCV. In this study, we used amplicon-based deep-sequencing to investigate the viral intra-host population composition of the genomic regions encoding the surface glycoproteins E1 and E2. Patterns of E1E2 substitutional evolution were compared in longitudinally sampled EqHV-positive sera of naturally and experimentally infected horses and HCV-positive patients. Intra-host virus diversity was higher in chronically than in acutely infected horses, a pattern which was similar in the HCV-infected patients. However, overall glycoprotein variability was higher in HCV compared to EqHV. Additionally, selection pressure in HCV populations was higher, especially within the N-terminal region of E2, corresponding to the hypervariable region 1 (HVR1) in HCV. An alignment of glycoprotein sequences from diverse hepaciviruses identified the HVR1 as a unique characteristic of HCV: hepaciviruses from non-human species lack this region. Together, these data indicate that EqHV infection of horses could represent a powerful surrogate animal model to gain insights into hepaciviral evolution and HCVs HVR1-mediated immune evasion strategy.

Published
2022

27. Immune Response in Moderate to Critical Breakthrough COVID-19 Infection After mRNA Vaccination

Author

Paniskaki, Krystallenia, Anft, Moritz, Meister, Toni L., Marheinecke, Corinna, Pfaender, Stephanie, Skrzypczyk, Sarah, Seibert, Felix S., Thieme, Constantin J., Konik, Margarethe J., Dolff, Sebastian, Anastasiou, Olympia, Holzer, Bodo, Dittmer, Ulf, Queren, Christine, Fricke, Lutz, Rohn, Hana, Westhoff, Timm H., Witzke, Oliver, Stervbo, Ulrik, Roch, Toralf, and Babel, Nina

Subjects
Adult, CD4-Positive T-Lymphocytes, Male, COVID-19 Vaccines, Coronavirus M Proteins, mRNA, breakthrough infection, T cells, Antibody Affinity, Medizin, CD8-Positive T-Lymphocytes, Antibodies, Viral, vaccine, Coronavirus Nucleocapsid Proteins, Humans, neutralizing antibodies, BNT162 Vaccine, Aged, Aged, 80 and over, SARS-CoV-2, Vaccination, COVID-19, Middle Aged, Phosphoproteins, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus, Female, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit, 2019-nCoV Vaccine mRNA-1273
Abstract

SARS-CoV-2 variants of concern (VOCs) can trigger severe endemic waves and vaccine breakthrough infections (VBI). We analyzed the cellular and humoral immune response in 8 patients infected with the alpha variant, resulting in moderate to fatal COVID-19 disease manifestation, after double mRNA-based anti-SARS-CoV-2 vaccination. In contrast to the uninfected vaccinated control cohort, the diseased individuals had no detectable high-avidity spike (S)-reactive CD4+ and CD8+ T cells against the alpha variant and wild type (WT) at disease onset, whereas a robust CD4+ T-cell response against the N- and M-proteins was generated. Furthermore, a delayed alpha S-reactive high-avidity CD4+ T-cell response was mounted during disease progression. Compared to the vaccinated control donors, these patients also had lower neutralizing antibody titers against the alpha variant at disease onset. The delayed development of alpha S-specific cellular and humoral immunity upon VBI indicates reduced immunogenicity against the S-protein of the alpha VOC, while there was a higher and earlier N- and M-reactive T-cell response. Our findings do not undermine the current vaccination strategies but underline a potential need for the inclusion of VBI patients in alternative vaccination strategies and additional antigenic targets in next-generation SARS-CoV-2 vaccines. CA extern

Published
2022

28. sj-docx-1-tan-10.1177_17562864221141505 – Supplemental material for Preserved T-cell response in anti-CD20-treated multiple sclerosis patients following SARS-CoV-2 vaccination

Author

Faissner, Simon, Heitmann, Neele, Rohling, Ricarda, Ceylan, Ulas, Bongert, Marielena, Plaza-Sirvent, Carlos, Marheinecke, Corinna, Pedreiturria, Xiomara, Ayzenberg, Ilya, Hellwig, Kerstin, Schmitz, Ingo, Pfaender, Stephanie, and Gold, Ralf

Subjects
FOS: Clinical medicine, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified, 110904 Neurology and Neuromuscular Diseases
Abstract

Supplemental material, sj-docx-1-tan-10.1177_17562864221141505 for Preserved T-cell response in anti-CD20-treated multiple sclerosis patients following SARS-CoV-2 vaccination by Simon Faissner, Neele Heitmann, Ricarda Rohling, Ulas Ceylan, Marielena Bongert, Carlos Plaza-Sirvent, Corinna Marheinecke, Xiomara Pedreiturria, Ilya Ayzenberg, Kerstin Hellwig, Ingo Schmitz, Stephanie Pfaender and Ralf Gold in Therapeutic Advances in Neurological Disorders

Published
2022
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30. Differential interferon-α subtype induced immune signatures are associated with suppression of SARS-CoV-2 infection

Author

Schuhenn, Jonas, primary, Meister, Toni Luise, additional, Todt, Daniel, additional, Bracht, Thilo, additional, Schork, Karin, additional, Billaud, Jean-Noel, additional, Elsner, Carina, additional, Heinen, Natalie, additional, Karakoese, Zehra, additional, Haid, Sibylle, additional, Kumar, Sriram, additional, Brunotte, Linda, additional, Eisenacher, Martin, additional, Di, Yunyun, additional, Lew, Jocelyne, additional, Falzarano, Darryl, additional, Chen, Jieliang, additional, Yuan, Zhenghong, additional, Pietschmann, Thomas, additional, Wiegmann, Bettina, additional, Uebner, Hendrik, additional, Taube, Christian, additional, Le-Trilling, Vu Thuy Khanh, additional, Trilling, Mirko, additional, Krawczyk, Adalbert, additional, Ludwig, Stephan, additional, Sitek, Barbara, additional, Steinmann, Eike, additional, Dittmer, Ulf, additional, Lavender, Kerry J., additional, Sutter, Kathrin, additional, and Pfaender, Stephanie, additional

Published
2022
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31. Immune Response in Moderate to Critical Breakthrough COVID-19 Infection After mRNA Vaccination

Author

Paniskaki, Krystallenia, primary, Anft, Moritz, additional, Meister, Toni L., additional, Marheinecke, Corinna, additional, Pfaender, Stephanie, additional, Skrzypczyk, Sarah, additional, Seibert, Felix S., additional, Thieme, Constantin J., additional, Konik, Margarethe J., additional, Dolff, Sebastian, additional, Anastasiou, Olympia, additional, Holzer, Bodo, additional, Dittmer, Ulf, additional, Queren, Christine, additional, Fricke, Lutz, additional, Rohn, Hana, additional, Westhoff, Timm H., additional, Witzke, Oliver, additional, Stervbo, Ulrik, additional, Roch, Toralf, additional, and Babel, Nina, additional

Published
2022
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32. Preserved T-cell response in anti-CD20-treated multiple sclerosis patients following SARS-CoV-2 vaccination

Author

Faissner, Simon, primary, Heitmann, Neele, additional, Rohling, Ricarda, additional, Ceylan, Ulas, additional, Bongert, Marielena, additional, Plaza-Sirvent, Carlos, additional, Marheinecke, Corinna, additional, Pedreiturria, Xiomara, additional, Ayzenberg, Ilya, additional, Hellwig, Kerstin, additional, Schmitz, Ingo, additional, Pfaender, Stephanie, additional, and Gold, Ralf, additional

Published
2022
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33. A genome-wide CRISPR screen identifies interactors of the autophagy pathway as conserved coronavirus targets

Author

Kratzel, Annika, primary, Kelly, Jenna N., additional, V’kovski, Philip, additional, Portmann, Jasmine, additional, Brüggemann, Yannick, additional, Todt, Daniel, additional, Ebert, Nadine, additional, Shrestha, Neeta, additional, Plattet, Philippe, additional, Staab-Weijnitz, Claudia A., additional, von Brunn, Albrecht, additional, Steinmann, Eike, additional, Dijkman, Ronald, additional, Zimmer, Gert, additional, Pfaender, Stephanie, additional, and Thiel, Volker, additional

Published
2021
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34. Impaired Humoral but Substantial Cellular Immune Response to Variants of Concern B1.1.7 and B.1.351 in Hemodialysis Patients after Vaccination with BNT162b2

Author

Thieme, Constantin J., primary, Blazquez-Navarro, Arturo, additional, Safi, Lema, additional, Kaliszczyk, Sviatlana, additional, Paniskaki, Krystallenia, additional, Neumann, Isabel E., additional, Schmidt, Kita, additional, Stockhausen, Mara, additional, Hörstrup, Jan, additional, Cinkilic, Ocan, additional, Flitsch-Kiefner, Linus, additional, Meister, Toni L., additional, Marheinecke, Corinna, additional, Pfaender, Stephanie, additional, Steinmann, Eike, additional, Seibert, Felix S., additional, Stervbo, Ulrik, additional, Westhoff, Timm H., additional, Roch, Toralf, additional, and Babel, Nina, additional

Published
2021
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35. Turmeric Root and Its Bioactive Ingredient Curcumin Effectively Neutralize SARS-CoV-2 In Vitro

Author

Bormann, Maren, Alt, Mira, Schipper, Leonie, Sand, Lukas van de, Le-Trilling, Vu Thuy Khanh, Rink, Lydia, Heinen, Natalie, Madel, Rabea Julia, Otte, Mona, Wuensch, Korbinian, Heilingloh, Christiane Silke, Mueller, Thorsten, Dittmer, Ulf, Elsner, Carina, Pfaender, Stephanie, Trilling, Mirko, Witzke, Oliver, and Krawczyk, Adalbert

Subjects
Curcumin, Medizin, Antiviral Agents, Microbiology, Article, Cell Line, Curcuma longa, Curcuma, Medizinische Fakultät » Universitätsklinikum Essen » Klinik für Infektiologie, Chlorocebus aethiops, Animals, Humans, curcumin, ddc:610, Vero Cells, Plant Extracts, SARS-CoV-2, COVID-19, Medizinische Fakultät » Universitätsklinikum Essen » Institut für Virologie, antiviral, QR1-502, COVID-19 Drug Treatment, turmeric root, Dietary Supplements, herbal medicine, Medicine, Traditional
Abstract

Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19). The availability of effective and well-tolerated antiviral drugs for the treatment of COVID-19 patients is still very limited. Traditional herbal medicines elicit antiviral activity against various viruses and might therefore represent a promising option for the complementary treatment of COVID-19 patients. The application of turmeric root in herbal medicine has a very long history. Its bioactive ingredient curcumin shows a broad-spectrum antimicrobial activity. In the present study, we investigated the antiviral activity of aqueous turmeric root extract, the dissolved content of a curcumin-containing nutritional supplement capsule, and pure curcumin against SARS-CoV-2. Turmeric root extract, dissolved turmeric capsule content, and pure curcumin effectively neutralized SARS-CoV-2 at subtoxic concentrations in Vero E6 and human Calu-3 cells. Furthermore, curcumin treatment significantly reduced SARS-CoV-2 RNA levels in cell culture supernatants. Our data uncover curcumin as a promising compound for complementary COVID-19 treatment. Curcumin concentrations contained in turmeric root or capsules used as nutritional supplements completely neutralized SARS-CoV-2 in vitro. Our data argue in favor of appropriate and carefully monitored clinical studies that vigorously test the effectiveness of complementary treatment of COVID-19 patients with curcumin-containing products. OA Förderung 2021

Published
2021

36. Superior cellular and humoral immunity toward SARS-CoV-2 reference and alpha and beta VOC strains in COVID-19 convalescent as compared to the prime boost BNT162b2-vaccinated dialysis patients

Author

Blazquez-Navarro, Arturo, Safi, Lema, Meister, Toni L., Thieme, Constantin J., Kaliszczyk, Sviatlana, Paniskaki, Krystallenia, Stockhausen, Mara, Hörstrup, Jan, Cinkilic, Okan, Flitsch-Kiefner, Linus, Marheinecke, Corinna, Steinmann, Eike, Seibert, Felix S., Stervbo, Ulrik, Westhoff, Timm H., Pfaender, Stephanie, Roch, Toralf, and Babel, Nina

Published
2021
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37. Turmeric Root and Its Bioactive Ingredient Curcumin Effectively Neutralize SARS-CoV-2 In Vitro

Author

Bormann, Maren, primary, Alt, Mira, additional, Schipper, Leonie, additional, van de Sand, Lukas, additional, Le-Trilling, Vu Thuy Khanh, additional, Rink, Lydia, additional, Heinen, Natalie, additional, Madel, Rabea Julia, additional, Otte, Mona, additional, Wuensch, Korbinian, additional, Heilingloh, Christiane Silke, additional, Mueller, Thorsten, additional, Dittmer, Ulf, additional, Elsner, Carina, additional, Pfaender, Stephanie, additional, Trilling, Mirko, additional, Witzke, Oliver, additional, and Krawczyk, Adalbert, additional

Published
2021
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38. SARS-CoV-2 N gene dropout and N gene Ct value shift as indicator for the presence of B.1.1.7 lineage in a commercial multiplex PCR assay

Author

Wollschläger, Paul, primary, Todt, Daniel, additional, Gerlitz, Nadja, additional, Pfaender, Stephanie, additional, Bollinger, Thomas, additional, Sing, Andreas, additional, Dangel, Alexandra, additional, Ackermann, Nickolaus, additional, Korn, Klaus, additional, Ensser, Armin, additional, Steinmann, Eike, additional, Buhl, Michael, additional, and Steinmann, Joerg, additional

Published
2021
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42. Immune response in ofatumumab treated multiple sclerosis patients aft er SARS-CoV-2 vaccination.

Author

Faissner, Simon, Heitmann, Neele, Plaza-Sirvent, Carlos, Trendelenburg, Paulina, Ceylan, Ulas, Motte, Jeremias, Bessen, Clara, Urlaub, Doris, Watzl, Carsten, Overheu, Oliver, Reinacher-Schick, Anke, Hellwig, Kerstin, Pfaender, Stephanie, Schmitz, Ingo, and Gold, Ralf

Subjects
IMMUNE response, HUMORAL immunity, REGULATORY T cells, MULTIPLE sclerosis, SARS-CoV-2
Abstract

Objective: The pandemic induced by SARS-CoV-2 has huge implications for patients with immunosuppression that is caused by disorders or specific treatments. Especially approaches targeting B cells via anti-CD20 therapy are associated with impaired humoral immune response but sustained cellular immunity. Ofatumumab is a human anti-CD20 directed antibody applied in low dosages subcutaneously, recently licensed for Multiple Sclerosis (MS). Effects of early ofatumumab treatment on alterations of immune cell composition and immune response towards SARS-CoV-2 are incompletely understood. Methods: We here investigated immune cell alterations in early ofatumumab (Ofa) treated patients and effects on humoral (titer, neutralization capacity against wild type, Delta and Omicron) and cellular immune responses in Ofa treated MS patients following a third vaccination against SARS-CoV-2 compared to healthy controls. Results: We show that a mean treatment duration of three months in the Ofa group led to near complete B cell depletion in line with altered composition of certain CD4+ T cell subpopulations such as enhanced frequencies of naive and a decrease of non-suppressive regulatory T cells (Tregs). Titer and neutralization capacity against SARS-CoV-2 variants was impaired while cellular immune response was sustained, characterized by a strong T helper 1 profile (Th1). Interpretation: In summary, low dosage ofatumumab treatment elicits sustained depletion of B cells in line with alterations of immune cells, mainly Tregs. This is associated with impaired humoral immune response towards SARS-CoV-2 vaccination but preserved, Th1 driven cellular immunity adding crucial information regarding early effects of low dosage anti-CD20 therapy on humoral and cellular immunity. [ABSTRACT FROM AUTHOR]

Published
2022
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46. Conserved requirement of autophagy-related effectors during coronavirus replication.

Author

Brüggemann, Yannick, Kratzel, Annika, Almeida, Lea, Kelly, Jenna N., Thiel, Volker, and Pfaender, Stephanie

Subjects
CORONAVIRUSES, COVID-19, LIFE cycles (Biology), SARS virus, MERS coronavirus, SARS-CoV-2
Abstract

The recurrence of zoonotic transmission events highlights the need for novel treatment strategies against emerging coronaviruses (CoVs), namely SARS-CoV, MERS-CoV and most notably SARS-CoV-2. Our recently performed genome-wide CRISPR knockout screen revealed a list of conserved pan-coronavirus as well as MERS-CoV or HCoV-229E-specific host dependency factors (HDF) essential during the viral life cycle. Intriguingly, we identified the macroautophagy/autophagy pathway-regulating immunophilins FKBP8, TMEM41B, and MINAR1 as conserved MERS-CoV, HCoV-229E, SARS-CoV, and SARS-CoV-2 host factors, which further constitute potential targets for therapeutic intervention by clinically approved drugs. [ABSTRACT FROM AUTHOR]

Published
2023
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47. COVID-19-Induced ARDS Is Associated with Decreased Frequency of Activated Memory/Effector T Cells Expressing CD11a++

Author

Anft, Moritz, primary, Paniskaki, Krystallenia, additional, Blazquez-Navarro, Arturo, additional, Doevelaar, Adrian, additional, Seibert, Felix S., additional, Hölzer, Bodo, additional, Skrzypczyk, Sarah, additional, Kohut, Eva, additional, Kurek, Julia, additional, Zapka, Jan, additional, Wehler, Patrizia, additional, Kaliszczyk, Sviatlana, additional, Bajda, Sharon, additional, Thieme, Constantin J., additional, Roch, Toralf, additional, Konik, Margarethe Justine, additional, Berger, Marc Moritz, additional, Brenner, Thorsten, additional, Kölsch, Uwe, additional, Meister, Toni L., additional, Pfaender, Stephanie, additional, Steinmann, Eike, additional, Tempfer, Clemens, additional, Watzl, Carsten, additional, Dolff, Sebastian, additional, Dittmer, Ulf, additional, Abou-El-Enein, Mohamed, additional, Westhoff, Timm H., additional, Witzke, Oliver, additional, Stervbo, Ulrik, additional, and Babel, Nina, additional

Published
2020
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48. Immune monitoring facilitates the clinical decision in multifocal COVID-19 of a pancreas-kidney transplant patient

Author

Babel, Nina, primary, Anft, Moritz, additional, Blazquez-Navarro, Arturo, additional, Doevelaar, Adrian A.N., additional, Seibert, Felix S., additional, Bauer, Frederic, additional, Rohn, Benjamin J., additional, Hoelzer, Bodo, additional, Thieme, Constantin J., additional, Roch, Toralf, additional, Meister, Toni L., additional, Pfaender, Stephanie, additional, Steinmann, Eike, additional, Dittmer, Ulf, additional, Schenker, Peter, additional, Amann, Kerstin, additional, Viebahn, Richard, additional, Stervbo, Ulrik, additional, and Westhoff, Timm H., additional

Published
2020
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49. Rapid Quantification of SARS-CoV-2-Neutralizing Antibodies Using Propagation-Defective Vesicular Stomatitis Virus Pseudotypes

Author

Zettl, Ferdinand, primary, Meister, Toni Luise, additional, Vollmer, Tanja, additional, Fischer, Bastian, additional, Steinmann, Jörg, additional, Krawczyk, Adalbert, additional, V’kovski, Philip, additional, Todt, Daniel, additional, Steinmann, Eike, additional, Pfaender, Stephanie, additional, and Zimmer, Gert, additional

Published
2020
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50. Comparison of Different In Situ Hybridization Techniques for the Detection of Various RNA and DNA Viruses

Author

Pfankuche, Vanessa M., Hahn, Kerstin, Bodewes, Rogier, Hansmann, Florian, Habierski, André, Haverkamp, Ann Kathrin, Pfaender, Stephanie, Walter, Stephanie, Baechlein, Christine, Postel, Alexander, Steinmann, Eike, Becher, Paul, Osterhaus, Albert, Baumgärtner, Wolfgang, Puff, Christina, Virology, LS GZ Landbouwhuisdieren, and dFAH I&I

Subjects
virus discovery, Chromogenic in situ hybridization, RNA virus, fast red, digoxigenin, Fast red, lcsh:QR1-502, virus diseases, Fluorescent in situ hybridization, lcsh:Microbiology, Infectious Diseases, fluorescent in situ hybridization, Virology, DNA virus, chromogenic in situ hybridization, Virus discovery, Digoxigenin
Abstract

In situ hybridization (ISH) is a technique to determine potential correlations between viruses and lesions. The aim of the study was to compare ISH techniques for the detection of various viruses in different tissues. Tested RNA viruses include atypical porcine pestivirus (APPV) in the cerebellum of pigs, equine and bovine hepacivirus (EqHV, BovHepV) in the liver of horses and cattle, respectively, and Schmallenberg virus (SBV) in the cerebrum of goats. Examined DNA viruses comprise canine bocavirus 2 (CBoV-2) in the intestine of dogs, porcine bocavirus (PBoV) in the spinal cord of pigs and porcine circovirus 2 (PCV-2) in cerebrum, lymph node, and lung of pigs. ISH with self-designed digoxigenin-labelled RNA probes revealed a positive signal for SBV, CBoV-2, and PCV-2, whereas it was lacking for APPV, BovHepV, EqHV, and PBoV. Commercially produced digoxigenin-labelled DNA probes detected CBoV-2 and PCV-2, but failed to detect PBoV. ISH with a commercially available fluorescent ISH (FISH)-RNA probe mix identified nucleic acids of all tested viruses. The detection rate and the cell-associated positive area using the FISH-RNA probe mix was highest compared to the results using other probes and protocols, representing a major benefit of this method. Nevertheless, there are differences in costs and procedure time.

Published
2018
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