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Marylyn Addo
I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany

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Journal article
Published: 09 July 2021 in Journal of Clinical Medicine
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In COVID-19, guidelines recommend a urinalysis on hospital admission as SARS-CoV-2 renal tropism, post-mortem, was associated with disease severity and mortality. Following the hypothesis from our pilot study, we now validate an algorithm harnessing urinalysis to predict the outcome and the need for ICU resources on admission to hospital. Patients were screened for urinalysis, serum albumin (SA) and antithrombin III activity (AT-III) obtained prospectively on admission. The risk for an unfavorable course was categorized as (1) “low”, (2) “intermediate” or (3) “high”, depending on (1) normal urinalysis, (2) abnormal urinalysis with SA ≥ 2 g/dL and AT-III ≥ 70%, or (3) abnormal urinalysis with SA or AT-III abnormality. Time to ICU admission or death served as the primary endpoint. Among 223 screened patients, 145 were eligible for enrollment, 43 falling into the low, 84 intermediate, and 18 into high-risk categories. An abnormal urinalysis significantly elevated the risk for ICU admission or death (63.7% vs. 27.9%; HR 2.6; 95%-CI 1.4 to 4.9; p = 0.0020) and was 100% in the high-risk group. Having an abnormal urinalysis was associated with mortality, a need for mechanical ventilation, extra-corporeal membrane oxygenation or renal replacement therapy. In conclusion, our data confirm that COVID-19-associated urine abnormalities on admission predict disease aggravation and the need for ICU (ClinicalTrials.gov number NCT04347824).

ACS Style

Oliver Gross; Onnen Moerer; Thomas Rauen; Jan Böckhaus; Elion Hoxha; Achim Jörres; Matthias Kamm; Amin Elfanish; Wolfram Windisch; Michael Dreher; Juergen Floege; Stefan Kluge; Christian Schmidt-Lauber; Jan-Eric Turner; Samuel Huber; Marylyn Addo; Simone Scheithauer; Tim Friede; Gerald Braun; Tobias Huber; Sabine Blaschke. Validation of a Prospective Urinalysis-Based Prediction Model for ICU Resources and Outcome of COVID-19 Disease: A Multicenter Cohort Study. Journal of Clinical Medicine 2021, 10, 3049 .

AMA Style

Oliver Gross, Onnen Moerer, Thomas Rauen, Jan Böckhaus, Elion Hoxha, Achim Jörres, Matthias Kamm, Amin Elfanish, Wolfram Windisch, Michael Dreher, Juergen Floege, Stefan Kluge, Christian Schmidt-Lauber, Jan-Eric Turner, Samuel Huber, Marylyn Addo, Simone Scheithauer, Tim Friede, Gerald Braun, Tobias Huber, Sabine Blaschke. Validation of a Prospective Urinalysis-Based Prediction Model for ICU Resources and Outcome of COVID-19 Disease: A Multicenter Cohort Study. Journal of Clinical Medicine. 2021; 10 (14):3049.

Chicago/Turabian Style

Oliver Gross; Onnen Moerer; Thomas Rauen; Jan Böckhaus; Elion Hoxha; Achim Jörres; Matthias Kamm; Amin Elfanish; Wolfram Windisch; Michael Dreher; Juergen Floege; Stefan Kluge; Christian Schmidt-Lauber; Jan-Eric Turner; Samuel Huber; Marylyn Addo; Simone Scheithauer; Tim Friede; Gerald Braun; Tobias Huber; Sabine Blaschke. 2021. "Validation of a Prospective Urinalysis-Based Prediction Model for ICU Resources and Outcome of COVID-19 Disease: A Multicenter Cohort Study." Journal of Clinical Medicine 10, no. 14: 3049.

Journal article
Published: 24 May 2021 in Journal of Clinical Medicine
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In this study, we directly compared coronavirus disease 2019 (COVID-19) patients hospitalized during the first (27 February–28 July 2020) and second (29 July–31 December 2020) wave of the pandemic at a large tertiary center in northern Germany. Patients who presented during the first (n = 174) and second (n = 331) wave did not differ in age (median [IQR], 59 years [46, 71] vs. 58 years [42, 73]; p = 0.82) or age-adjusted Charlson Comorbidity Index (median [IQR], 2 [1, 4] vs. 2 [0, 4]; p = 0.50). During the second wave, a higher proportion of patients were treated as outpatients (11% [n = 20] vs. 20% [n = 67]), fewer patients were admitted to the intensive care unit (43% [n = 75] vs. 29% [n = 96]), and duration of hospitalization was significantly shorter (median days [IQR], 14 [8, 34] vs. 11 [5, 19]; p< 0.001). However, in-hospital mortality was high throughout the pandemic and did not differ between the two periods (16% [n = 27] vs. 16% [n = 54]; p = 0.89). While novel treatment strategies and increased knowledge about the clinical management of COVID-19 may have resulted in a less severe disease course in some patients, in-hospital mortality remained unaltered at a high level. These findings highlight the unabated need for efforts to hamper severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) transmission, to increase vaccination coverage, and to develop novel treatment strategies to prevent mortality and decrease morbidity.

ACS Style

Thomas Brehm; Andreas Heyer; Kevin Roedl; Dominik Jarczak; Axel Nierhaus; Michael Nentwich; Marc van der Meirschen; Alexander Schultze; Martin Christner; Walter Fiedler; Nicolaus Kröger; Tobias Huber; Hans Klose; Martina Sterneck; Sabine Jordan; Benno Kreuels; Stefan Schmiedel; Marylyn Addo; Samuel Huber; Ansgar Lohse; Stefan Kluge; Julian Schulze Zur Wiesch. Patient Characteristics and Clinical Course of COVID-19 Patients Treated at a German Tertiary Center during the First and Second Waves in the Year 2020. Journal of Clinical Medicine 2021, 10, 2274 .

AMA Style

Thomas Brehm, Andreas Heyer, Kevin Roedl, Dominik Jarczak, Axel Nierhaus, Michael Nentwich, Marc van der Meirschen, Alexander Schultze, Martin Christner, Walter Fiedler, Nicolaus Kröger, Tobias Huber, Hans Klose, Martina Sterneck, Sabine Jordan, Benno Kreuels, Stefan Schmiedel, Marylyn Addo, Samuel Huber, Ansgar Lohse, Stefan Kluge, Julian Schulze Zur Wiesch. Patient Characteristics and Clinical Course of COVID-19 Patients Treated at a German Tertiary Center during the First and Second Waves in the Year 2020. Journal of Clinical Medicine. 2021; 10 (11):2274.

Chicago/Turabian Style

Thomas Brehm; Andreas Heyer; Kevin Roedl; Dominik Jarczak; Axel Nierhaus; Michael Nentwich; Marc van der Meirschen; Alexander Schultze; Martin Christner; Walter Fiedler; Nicolaus Kröger; Tobias Huber; Hans Klose; Martina Sterneck; Sabine Jordan; Benno Kreuels; Stefan Schmiedel; Marylyn Addo; Samuel Huber; Ansgar Lohse; Stefan Kluge; Julian Schulze Zur Wiesch. 2021. "Patient Characteristics and Clinical Course of COVID-19 Patients Treated at a German Tertiary Center during the First and Second Waves in the Year 2020." Journal of Clinical Medicine 10, no. 11: 2274.

Preprint content
Published: 20 April 2021
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Overwhelming activation of T cells in acute malaria is associated with severe outcomes. Thus, counter-regulation by anti-inflammatory mechanisms is indispensable for an optimal resolution of disease. Using Plasmodium berghei ANKA (PbA) infection of C57BL/6 mice, we performed a comprehensive analysis of co-inhibitory molecules expressed on CD4+ and CD8+ T cells using an unbiased cluster analysis approach. We identified similar T cell clusters co-expressing several co-inhibitory molecules like programmed cell death protein 1 (PD-1) and lymphocyte activation gene 3 (LAG-3) in the CD4+ and the CD8+ T cell compartment. Interestingly, despite expressing co-inhibitory molecules, which are associated with T cell exhaustion in chronic settings, these T cells were more functional compared to activated T cells that were negative for co-inhibitory molecules. However, T cells expressing high levels of PD-1 and LAG-3 also conferred suppressive capacity and thus resembled type I regulatory T cells. To our knowledge, this is the first description of malaria-induced CD8+ T cells with suppressive capacity. In conclusion, we demonstrate that malaria-induced T cells expressing co-inhibitory molecules are not exhausted but acquire additional suppressive capacity, which might represent an immune regulatory pathway to prevent further activation of T cells during acute malaria.

ACS Style

Johannes Brandi; Cari Lehmann; Lea-Christina Kaminski; Julian Schulze Zur Wiesch; Marylyn Addo; Michael Ramharter; Maria Mackroth; Thomas Jacobs; Mathias Riehn. T cells expressing multiple co-inhibitory molecules in acute malaria are not exhausted but exert a suppressive function. 2021, 1 .

AMA Style

Johannes Brandi, Cari Lehmann, Lea-Christina Kaminski, Julian Schulze Zur Wiesch, Marylyn Addo, Michael Ramharter, Maria Mackroth, Thomas Jacobs, Mathias Riehn. T cells expressing multiple co-inhibitory molecules in acute malaria are not exhausted but exert a suppressive function. . 2021; ():1.

Chicago/Turabian Style

Johannes Brandi; Cari Lehmann; Lea-Christina Kaminski; Julian Schulze Zur Wiesch; Marylyn Addo; Michael Ramharter; Maria Mackroth; Thomas Jacobs; Mathias Riehn. 2021. "T cells expressing multiple co-inhibitory molecules in acute malaria are not exhausted but exert a suppressive function." , no. : 1.

Communication
Published: 12 April 2021 in Viruses
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So far, only a few reports about reinfections with SARS-CoV-2 have been published, and they often lack detailed immunological and virological data. We report about a SARS-CoV-2 reinfection with a genetically distinct SARS-CoV-2 variant in an immunocompetent female healthcare worker that has led to a mild disease course. No obvious viral escape mutations were observed in the second virus variant. The infectious virus was shed from the patient during the second infection episode despite the presence of neutralizing antibodies in her blood. Our data indicate that a moderate immune response after the first infection, but not a viral escape, did allow for reinfection and live virus shedding.

ACS Style

Thomas Brehm; Susanne Pfefferle; Ronald von Possel; Robin Kobbe; Dominik Nörz; Stefan Schmiedel; Adam Grundhoff; Flaminia Olearo; Petra Emmerich; Alexis Robitaille; Thomas Günther; Platon Braun; Gabriele Andersen; Johannes Knobloch; Marylyn Addo; Ansgar Lohse; Martin Aepfelbacher; Nicole Fischer; Julian Schulze Zur Wiesch; Marc Lütgehetmann. SARS-CoV-2 Reinfection in a Healthcare Worker Despite the Presence of Detectable Neutralizing Antibodies. Viruses 2021, 13, 661 .

AMA Style

Thomas Brehm, Susanne Pfefferle, Ronald von Possel, Robin Kobbe, Dominik Nörz, Stefan Schmiedel, Adam Grundhoff, Flaminia Olearo, Petra Emmerich, Alexis Robitaille, Thomas Günther, Platon Braun, Gabriele Andersen, Johannes Knobloch, Marylyn Addo, Ansgar Lohse, Martin Aepfelbacher, Nicole Fischer, Julian Schulze Zur Wiesch, Marc Lütgehetmann. SARS-CoV-2 Reinfection in a Healthcare Worker Despite the Presence of Detectable Neutralizing Antibodies. Viruses. 2021; 13 (4):661.

Chicago/Turabian Style

Thomas Brehm; Susanne Pfefferle; Ronald von Possel; Robin Kobbe; Dominik Nörz; Stefan Schmiedel; Adam Grundhoff; Flaminia Olearo; Petra Emmerich; Alexis Robitaille; Thomas Günther; Platon Braun; Gabriele Andersen; Johannes Knobloch; Marylyn Addo; Ansgar Lohse; Martin Aepfelbacher; Nicole Fischer; Julian Schulze Zur Wiesch; Marc Lütgehetmann. 2021. "SARS-CoV-2 Reinfection in a Healthcare Worker Despite the Presence of Detectable Neutralizing Antibodies." Viruses 13, no. 4: 661.

Journal article
Published: 10 April 2021
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ACS Style

Julian J. Gabor; Andrea Kreidenweiss; Stefan Weber; Moaaz Salama; Mihaly Sulyok; Zita Sulyok; Erik Koehne; Meral Esen; Benno Kreuels; Parichehr Shamsrizi; Erwin Biecker; Benjamin Mordmüller; Christoph P. Berg; Stefano Fusco; Carsten Köhler; Stefan Kubicka; Jens Leitlein; Marylyn Addo; Michael Ramharter; Matthias Schwab; Alfred Lennart Bissinger; Thirumalaisamy P. Velavan; Sanjeev Krishna; Peter G. Kremsner. A call to caution when hydroxychloroquine is given to elderly COVID-19 patients. 2021, 1 .

AMA Style

Julian J. Gabor, Andrea Kreidenweiss, Stefan Weber, Moaaz Salama, Mihaly Sulyok, Zita Sulyok, Erik Koehne, Meral Esen, Benno Kreuels, Parichehr Shamsrizi, Erwin Biecker, Benjamin Mordmüller, Christoph P. Berg, Stefano Fusco, Carsten Köhler, Stefan Kubicka, Jens Leitlein, Marylyn Addo, Michael Ramharter, Matthias Schwab, Alfred Lennart Bissinger, Thirumalaisamy P. Velavan, Sanjeev Krishna, Peter G. Kremsner. A call to caution when hydroxychloroquine is given to elderly COVID-19 patients. . 2021; ():1.

Chicago/Turabian Style

Julian J. Gabor; Andrea Kreidenweiss; Stefan Weber; Moaaz Salama; Mihaly Sulyok; Zita Sulyok; Erik Koehne; Meral Esen; Benno Kreuels; Parichehr Shamsrizi; Erwin Biecker; Benjamin Mordmüller; Christoph P. Berg; Stefano Fusco; Carsten Köhler; Stefan Kubicka; Jens Leitlein; Marylyn Addo; Michael Ramharter; Matthias Schwab; Alfred Lennart Bissinger; Thirumalaisamy P. Velavan; Sanjeev Krishna; Peter G. Kremsner. 2021. "A call to caution when hydroxychloroquine is given to elderly COVID-19 patients." , no. : 1.

Journal article
Published: 06 April 2021 in Pathogens
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The current COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). A better understanding of its immunogenicity can be important for the development of improved diagnostics, therapeutics, and vaccines. Here, we report the longitudinal analysis of three COVID-19 patients with moderate (#1) and mild disease (#2 and #3). Antibody serum responses were analyzed using spike glycoprotein enzyme linked immunosorbent assay (ELISA), full-proteome peptide, and glycan microarrays. ELISA immunoglobulin A, G, and M (IgA, IgG, and IgM) signals increased over time for individuals #1 and #2, whereas #3 only showed no clear positive IgG and IgM result. In contrast, peptide microarrays showed increasing IgA/G signal intensity and epitope spread only in the moderate patient #1 over time, whereas early but transient IgA and stable IgG responses were observed in the two mild cases #2 and #3. Glycan arrays showed an interaction of antibodies to fragments of high-mannose and core N-glycans, present on the viral shield. In contrast to protein ELISA, microarrays allow for a deeper understanding of IgA, IgG, and IgM antibody responses to specific epitopes of the whole proteome and glycans of SARS-CoV-2 in parallel. In the future, this may help to better understand and to monitor vaccination programs and monoclonal antibodies as therapeutics.

ACS Style

Jasmin Heidepriem; Christine Dahlke; Robin Kobbe; René Santer; Till Koch; Anahita Fathi; Bruna Seco; My Ly; Stefan Schmiedel; Dorothee Schwinge; Sonia Serna; Katrin Sellrie; Niels-Christian Reichardt; Peter Seeberger; Marylyn Addo; Felix Loeffler; on behalf of the ID-UKE COVID-19 Study Group. Longitudinal Development of Antibody Responses in COVID-19 Patients of Different Severity with ELISA, Peptide, and Glycan Arrays: An Immunological Case Series. Pathogens 2021, 10, 438 .

AMA Style

Jasmin Heidepriem, Christine Dahlke, Robin Kobbe, René Santer, Till Koch, Anahita Fathi, Bruna Seco, My Ly, Stefan Schmiedel, Dorothee Schwinge, Sonia Serna, Katrin Sellrie, Niels-Christian Reichardt, Peter Seeberger, Marylyn Addo, Felix Loeffler, on behalf of the ID-UKE COVID-19 Study Group. Longitudinal Development of Antibody Responses in COVID-19 Patients of Different Severity with ELISA, Peptide, and Glycan Arrays: An Immunological Case Series. Pathogens. 2021; 10 (4):438.

Chicago/Turabian Style

Jasmin Heidepriem; Christine Dahlke; Robin Kobbe; René Santer; Till Koch; Anahita Fathi; Bruna Seco; My Ly; Stefan Schmiedel; Dorothee Schwinge; Sonia Serna; Katrin Sellrie; Niels-Christian Reichardt; Peter Seeberger; Marylyn Addo; Felix Loeffler; on behalf of the ID-UKE COVID-19 Study Group. 2021. "Longitudinal Development of Antibody Responses in COVID-19 Patients of Different Severity with ELISA, Peptide, and Glycan Arrays: An Immunological Case Series." Pathogens 10, no. 4: 438.

Communication
Published: 26 March 2021 in Tropical Medicine and Infectious Disease
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We report a case of Plasmodium falciparum malaria in a patient asymptomatically co-infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the current ongoing coronavirus pandemic, co-infections with unrelated life-threatening febrile conditions may pose a particular challenge to clinicians. The current situation increases the risk for cognitive biases in medical management.

ACS Style

Johannes Jochum; Benno Kreuels; Egbert Tannich; Samuel Huber; Julian Schulze Zur Wiesch; Stefan Schmiedel; Michael Ramharter; Marylyn Addo. Malaria in the Time of COVID-19: Do Not Miss the Real Cause of Illness. Tropical Medicine and Infectious Disease 2021, 6, 40 .

AMA Style

Johannes Jochum, Benno Kreuels, Egbert Tannich, Samuel Huber, Julian Schulze Zur Wiesch, Stefan Schmiedel, Michael Ramharter, Marylyn Addo. Malaria in the Time of COVID-19: Do Not Miss the Real Cause of Illness. Tropical Medicine and Infectious Disease. 2021; 6 (2):40.

Chicago/Turabian Style

Johannes Jochum; Benno Kreuels; Egbert Tannich; Samuel Huber; Julian Schulze Zur Wiesch; Stefan Schmiedel; Michael Ramharter; Marylyn Addo. 2021. "Malaria in the Time of COVID-19: Do Not Miss the Real Cause of Illness." Tropical Medicine and Infectious Disease 6, no. 2: 40.

Review
Published: 10 March 2021 in Vaccines
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We are in the midst of a pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19). SARS-CoV-2 has caused more than two million deaths after one year of the pandemic. The world is experiencing a deep economic recession. Safe and effective vaccines are needed to prevent further morbidity and mortality. Vaccine candidates against COVID-19 have been developed at an unprecedented speed, with more than 200 vaccine candidates currently under investigation. Among those, 20 candidates have entered the clinical Phase 3 to evaluate efficacy, and three have been approved by the European Medicines Agency. The aim of immunization is to act against infection, disease and/or transmission. However, the measurement of vaccine efficacy is challenging, as efficacy trials need to include large cohorts with verum and placebo cohorts. In the future, this will be even more challenging as further vaccine candidates will receive approval, an increasing number of humans will receive vaccinations and incidence might decrease. To evaluate novel and second-generation vaccine candidates, randomized placebo-controlled trials might not be appropriate anymore. Correlates of protection (CoP) could be an important tool to evaluate novel vaccine candidates, but vaccine-induced CoP have not been clearly defined for SARS-CoV-2 vaccines. In this review, we report on immunogenicity against natural SARS-CoV-2 infection, vaccine-induced immune responses and discuss immunological markers that can be linked to protection. By discussing the immunogenicity and efficacy of forerunner vaccines, we aim to give a comprehensive overview of possible efficacy measures and CoP.

ACS Style

Till Koch; Sibylle Mellinghoff; Parichehr Shamsrizi; Marylyn Addo; Christine Dahlke. Correlates of Vaccine-Induced Protection against SARS-CoV-2. Vaccines 2021, 9, 238 .

AMA Style

Till Koch, Sibylle Mellinghoff, Parichehr Shamsrizi, Marylyn Addo, Christine Dahlke. Correlates of Vaccine-Induced Protection against SARS-CoV-2. Vaccines. 2021; 9 (3):238.

Chicago/Turabian Style

Till Koch; Sibylle Mellinghoff; Parichehr Shamsrizi; Marylyn Addo; Christine Dahlke. 2021. "Correlates of Vaccine-Induced Protection against SARS-CoV-2." Vaccines 9, no. 3: 238.

Research article
Published: 23 February 2021 in Science Immunology
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Hyperinflammation contributes to lung injury and subsequent acute respiratory distress syndrome with high mortality in patients with severe coronavirus disease 2019 (COVID-19). To understand the underlying mechanisms involved in lung pathology, we investigated the role of the lung-specific immune response. We profiled immune cells in bronchoalveolar lavage fluid and blood collected from patients with severe COVID-19 and patients with bacterial pneumonia not associated with viral infection. By tracking T cell clones across tissues, we identified clonally expanded tissue-resident memory-like TH17 cells (TRM17 cells) in the lungs even after viral clearance. These TRM17 cells were characterized by a potentially pathogenic cytokine expression profile of IL17A and CSF2 (GM-CSF). Interactome analysis suggests that TRM17 cells can interact with lung macrophages and cytotoxic CD8+ T cells, which have been associated with disease severity and lung damage. High IL-17A and GM-CSF protein levels in the serum of patients with COVID-19 were associated with a more severe clinical course. Collectively, our study suggests that pulmonary TRM17 cells are one potential orchestrator of the hyperinflammation in severe COVID-19.

ACS Style

Yu Zhao; Christoph Kilian; Jan-Eric Turner; Lidia Bosurgi; Kevin Roedl; Patricia Bartsch; Ann-Christin Gnirck; Filippo Cortesi; Christoph Schultheiß; Malte Hellmig; Leon U.B. Enk; Fabian Hausmann; Alina Borchers; Milagros N. Wong; Hans-Joachim Paust; Francesco Siracusa; Nicola Scheibel; Marissa Herrmann; Elisa Rosati; Petra Bacher; Dominik Kylies; Dominik Jarczak; Marc Lütgehetmann; Susanne Pfefferle; Stefan Steurer; Julian Schulze Zur Wiesch; Victor G. Puelles; Jan-Peter Sperhake; Marylyn M. Addo; Ansgar W. Lohse; Mascha Binder; Samuel Huber; Tobias B. Huber; Stefan Kluge; Stefan Bonn; Ulf Panzer; Nicola Gagliani; Christian F. Krebs. Clonal expansion and activation of tissue-resident memory-like TH17 cells expressing GM-CSF in the lungs of patients with severe COVID-19. Science Immunology 2021, 6, eabf6692 .

AMA Style

Yu Zhao, Christoph Kilian, Jan-Eric Turner, Lidia Bosurgi, Kevin Roedl, Patricia Bartsch, Ann-Christin Gnirck, Filippo Cortesi, Christoph Schultheiß, Malte Hellmig, Leon U.B. Enk, Fabian Hausmann, Alina Borchers, Milagros N. Wong, Hans-Joachim Paust, Francesco Siracusa, Nicola Scheibel, Marissa Herrmann, Elisa Rosati, Petra Bacher, Dominik Kylies, Dominik Jarczak, Marc Lütgehetmann, Susanne Pfefferle, Stefan Steurer, Julian Schulze Zur Wiesch, Victor G. Puelles, Jan-Peter Sperhake, Marylyn M. Addo, Ansgar W. Lohse, Mascha Binder, Samuel Huber, Tobias B. Huber, Stefan Kluge, Stefan Bonn, Ulf Panzer, Nicola Gagliani, Christian F. Krebs. Clonal expansion and activation of tissue-resident memory-like TH17 cells expressing GM-CSF in the lungs of patients with severe COVID-19. Science Immunology. 2021; 6 (56):eabf6692.

Chicago/Turabian Style

Yu Zhao; Christoph Kilian; Jan-Eric Turner; Lidia Bosurgi; Kevin Roedl; Patricia Bartsch; Ann-Christin Gnirck; Filippo Cortesi; Christoph Schultheiß; Malte Hellmig; Leon U.B. Enk; Fabian Hausmann; Alina Borchers; Milagros N. Wong; Hans-Joachim Paust; Francesco Siracusa; Nicola Scheibel; Marissa Herrmann; Elisa Rosati; Petra Bacher; Dominik Kylies; Dominik Jarczak; Marc Lütgehetmann; Susanne Pfefferle; Stefan Steurer; Julian Schulze Zur Wiesch; Victor G. Puelles; Jan-Peter Sperhake; Marylyn M. Addo; Ansgar W. Lohse; Mascha Binder; Samuel Huber; Tobias B. Huber; Stefan Kluge; Stefan Bonn; Ulf Panzer; Nicola Gagliani; Christian F. Krebs. 2021. "Clonal expansion and activation of tissue-resident memory-like TH17 cells expressing GM-CSF in the lungs of patients with severe COVID-19." Science Immunology 6, no. 56: eabf6692.

Journal article
Published: 16 September 2020 in Pathogens
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Background: Hepatitis E virus (HEV) has been associated with immunological phenomena. Their clinical significance, however, still needs to be clarified, that is, whether cryoglobulins or autoantibodies impact overt disease in HEV-infected individuals. To better understand, we analyzed these different immune phenomena in three cohorts, each representing different types of HEV infection. Methods: The cohorts included: (i) immunocompetent patients with acute hepatitis E, (ii) immunosuppressed patients with chronic hepatitis E, and (iii) individuals with asymptomatic HEV infection. Together, they consisted of 57 individuals and were studied retrospectively for the presence of anti-nuclear antibodies (ANAs), cryoglobulins, and serum total IgG. They were then compared with a control cohort of 17 untreated patients with chronic hepatitis B virus (HBV) infection or hepatitis C virus (HCV) infection. Results: Thirteen (23%) were immunocompetent patients with acute hepatitis E (median alanine aminotransferase (ALT) = 872 U/L), 15 (26%) were immunosuppressed patients with chronic hepatitis E (median ALT = 137 U/L), and 29 (51%) were blood donors with asymptomatic HEV infection (median ALT = 35 U/L). Overall, 24% tested positive for elevated ANA titers of >1:160, and 11% presented with a specific ANA pattern. ANA detection was not associated with the type of HEV infection, IgG levels, sex, or age. All individuals tested negative for anti-mitochondrial antibodies, anti-neutrophil cytoplasmic antibodies, liver-kidney microsomal antibodies, anti-myeloperoxidase-, and anti-proteinase-3 antibodies. Five patients (9%) tested positive for cryoglobulins. Notably, cryoglobulinemia was present in overt hepatitis E (Groups (i) and (ii); one acute and four chronic HEV infections), but was not present in any of the asymptomatic blood donors (p = 0.02). The frequency of cryoglobulins and elevated ANAs did not differ significantly between HEV and HBV/HCV patients. Conclusion: In line with findings on HBV and HCV infections, we frequently observed detection of ANAs (24%) and cryoglobulins (9%) in association with HEV infections. The presence of cryoglobulins was limited to patients with overt hepatitis E. We add to the findings on the immune phenomena of hepatitis E.

ACS Style

Thomas Horvatits; Julian Schulze Zur Wiesch; Susanne Polywka; Gustav Buescher; Marc Lütgehetmann; Elaine Hussey; Karoline Horvatits; Sven Peine; Friedrich Haag; Marylyn M. Addo; Ansgar W. Lohse; Christina Weiler-Normann; Sven Pischke. Significance of Anti-Nuclear Antibodies and Cryoglobulins in Patients with Acute and Chronic HEV Infection. Pathogens 2020, 9, 755 .

AMA Style

Thomas Horvatits, Julian Schulze Zur Wiesch, Susanne Polywka, Gustav Buescher, Marc Lütgehetmann, Elaine Hussey, Karoline Horvatits, Sven Peine, Friedrich Haag, Marylyn M. Addo, Ansgar W. Lohse, Christina Weiler-Normann, Sven Pischke. Significance of Anti-Nuclear Antibodies and Cryoglobulins in Patients with Acute and Chronic HEV Infection. Pathogens. 2020; 9 (9):755.

Chicago/Turabian Style

Thomas Horvatits; Julian Schulze Zur Wiesch; Susanne Polywka; Gustav Buescher; Marc Lütgehetmann; Elaine Hussey; Karoline Horvatits; Sven Peine; Friedrich Haag; Marylyn M. Addo; Ansgar W. Lohse; Christina Weiler-Normann; Sven Pischke. 2020. "Significance of Anti-Nuclear Antibodies and Cryoglobulins in Patients with Acute and Chronic HEV Infection." Pathogens 9, no. 9: 755.

Journal article
Published: 20 August 2020 in Viruses
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The last seven years have seen the greatest surge of Ebola virus disease (EVD) cases in equatorial Africa, including the 2013–2016 epidemic in West Africa and the recent epidemics in the Democratic Republic of Congo (DRC). The vaccine clinical trials that took place in West Africa and the DRC, as well as follow-up studies in collaboration with EVD survivor communities, have for the first time allowed researchers to compare immune memory induced by natural infection and vaccination. These comparisons may be relevant to evaluate the putative effectiveness of vaccines and candidate medical countermeasures such as convalescent plasma transfer. In this study, we compared the long-term functionality of anti-EBOV glycoprotein (GP) antibodies from EVD survivors with that from volunteers who received the recombinant vesicular stomatitis virus vectored vaccine (rVSV-ZEBOV) during the Phase I clinical trial in Hamburg. Our study highlights important differences between EBOV vaccination and natural infection and provides a framework for comparison with other vaccine candidates.

ACS Style

Till Koch; Monika Rottstegge; Paula Ruibal; Sergio Gomez-Medina; Emily V. Nelson; Beatriz Escudero-Pérez; Matthias Pillny; My Linh Ly; Fara Raymond Koundouno; Joseph Akoi Bore; N’Faly Magassouba; Christine Dahlke; Stephan Günther; Miles W. Carroll; Marylyn M. Addo; César Muñoz-Fontela. Ebola Virus Disease Survivors Show More Efficient Antibody Immunity than Vaccines Despite Similar Levels of Circulating Immunoglobulins. Viruses 2020, 12, 915 .

AMA Style

Till Koch, Monika Rottstegge, Paula Ruibal, Sergio Gomez-Medina, Emily V. Nelson, Beatriz Escudero-Pérez, Matthias Pillny, My Linh Ly, Fara Raymond Koundouno, Joseph Akoi Bore, N’Faly Magassouba, Christine Dahlke, Stephan Günther, Miles W. Carroll, Marylyn M. Addo, César Muñoz-Fontela. Ebola Virus Disease Survivors Show More Efficient Antibody Immunity than Vaccines Despite Similar Levels of Circulating Immunoglobulins. Viruses. 2020; 12 (9):915.

Chicago/Turabian Style

Till Koch; Monika Rottstegge; Paula Ruibal; Sergio Gomez-Medina; Emily V. Nelson; Beatriz Escudero-Pérez; Matthias Pillny; My Linh Ly; Fara Raymond Koundouno; Joseph Akoi Bore; N’Faly Magassouba; Christine Dahlke; Stephan Günther; Miles W. Carroll; Marylyn M. Addo; César Muñoz-Fontela. 2020. "Ebola Virus Disease Survivors Show More Efficient Antibody Immunity than Vaccines Despite Similar Levels of Circulating Immunoglobulins." Viruses 12, no. 9: 915.

Journal article
Published: 11 August 2020 in Biomolecules
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Recently, the stabilization of the endothelium has been explicitly identified as a therapeutic goal in coronavirus disease 2019 (COVID-19). Adrecizumab is a first-in-class humanized monoclonal anti-Adrenomedullin (anti-ADM) antibody, targeting the sepsis- and inflammation-based vascular and capillary leakage. Within a “treatment on a named-patient basis” approach, Adrecizumab was administered to eight extreme-critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS). The patients received a single dose of Adrecizumab, which was administered between 1 and 3 days after the initiation of mechanical ventilation. The SOFA (median 12.5) and SAPS-II (median 39) scores clearly documented the population at highest risk. Moreover, six of the patients suffered from acute renal failure, of whom five needed renal replacement therapy. The length of follow-up ranged between 13 and 27 days. Following the Adrecizumab administration, one patient in the low-dose group died at day 4 due to fulminant pulmonary embolism, while four were in stable condition, and three were discharged from the intensive care unit (ICU). Within 12 days, the SOFA score, as well as the disease severity score (range 0–16, mirroring critical resources in the ICU, with higher scores indicating more severe illness), decreased in five out of the seven surviving patients (in all high-dose patients). The PaO2/FiO2 increased within 12 days, while the inflammatory parameters C-reactive protein, procalcitonin, and interleukin-6 decreased. Importantly, the mortality was lower than expected and calculated by the SOFA score. In conclusion, in this preliminary uncontrolled case series of eight shock patients with life-threatening COVID-19 and ARDS, the administration of Adrecizumab was followed by a favorable outcome. Although the non-controlled design and the small sample size preclude any definitive statement about the potential efficacy of Adrecizumab in critically ill COVID-19 patients, the results of this case series are encouraging.

ACS Style

Mahir Karakas; Dominik Jarczak; Martin Becker; Kevin Roedl; Marylyn M. Addo; Frauke Hein; Andreas Bergmann; Jens Zimmermann; Tim-Philipp Simon; Gernot Marx; Marc Lütgehetmann; Axel Nierhaus; Stefan Kluge. Targeting Endothelial Dysfunction in Eight Extreme-Critically Ill Patients with COVID-19 Using the Anti-Adrenomedullin Antibody Adrecizumab. Biomolecules 2020, 10, 1171 .

AMA Style

Mahir Karakas, Dominik Jarczak, Martin Becker, Kevin Roedl, Marylyn M. Addo, Frauke Hein, Andreas Bergmann, Jens Zimmermann, Tim-Philipp Simon, Gernot Marx, Marc Lütgehetmann, Axel Nierhaus, Stefan Kluge. Targeting Endothelial Dysfunction in Eight Extreme-Critically Ill Patients with COVID-19 Using the Anti-Adrenomedullin Antibody Adrecizumab. Biomolecules. 2020; 10 (8):1171.

Chicago/Turabian Style

Mahir Karakas; Dominik Jarczak; Martin Becker; Kevin Roedl; Marylyn M. Addo; Frauke Hein; Andreas Bergmann; Jens Zimmermann; Tim-Philipp Simon; Gernot Marx; Marc Lütgehetmann; Axel Nierhaus; Stefan Kluge. 2020. "Targeting Endothelial Dysfunction in Eight Extreme-Critically Ill Patients with COVID-19 Using the Anti-Adrenomedullin Antibody Adrecizumab." Biomolecules 10, no. 8: 1171.

Other
Published: 31 July 2020
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ObjectiveTo assess the effectiveness of multimodal infection control interventions in the prevention of SARS-CoV-2 infections in healthcare professionalsDesignSequential follow-up studySettingLargest tertiary care centre in northern GermanyParticipants1253 employees of the University Medical Center Hamburg-Eppendorf were sequentially assessed for the presence of SARS-CoV-2 IgG antibodies at the beginning of the covid-19 epidemic (20 March – 9 April), one month (20 April – 8 May), and another two months later (22 June – 24 July). Of those, 1026 were healthcare workers (HCWs) of whom 292 were directly involved in the care of covid-19 patients. During the study period, infection control interventions were deployed, those included i) strict barrier nursing of all known covid-19 patients including FFP2 (N95) masks, goggles, gloves, hoods and protective gowns, ii) visitor restrictions with access control at all hospital entries, iii) mandatory wearing of disposable face masks in all clinical settings, and iv) universal RT-PCR admission screening of patients.Main Outcome MeasuresSARS-CoV-2 IgG seroconversion rateResultsAt the initial screening, ten participants displayed significant IgG antibody ratios. Another ten individuals showed seroconversion at the second time point one month later, only two further participants seroconverted during the subsequent two months. The overall SARS-CoV-2 seroprevalence in the study cohort at the last follow-up was 1.8%, the seroconversion rate dropped from 0.81% to 0.08% per month despite a longer observation period. Amongst HCWs seropositivity was increased in those directly involved in the care of patients with SARS-CoV-2 infections (3.8%, n=11) compared to other HCWs (1.4%, n=10, P=0.025). However, after the adoption of all multimodal infection control interventions seroconversions were observed in only two more HCWs, neither of whom were involved in inpatient care.ConclusionMultimodal infection control and prevention interventions are highly effective in mitigating SARS-CoV-2 infections of healthcare professionals.

ACS Style

Thomas Theo Brehm; Dorothee Schwinge; Sibylle Lampalzer; Veronika Schlicker; Julia Kuechen; Michelle Thompson; Felix Ullrich; Samuel Huber; Stefan Schmiedel; Marylyn M Addo; Marc Luetgehetmann; Johannes K Knobloch; Julian Schulze Zur Wiesch; Ansgar W Lohse. High effectiveness of multimodal infection control interventions in preventing SARS-CoV-2 infections in healthcare professionals: a prospective longitudinal seroconversion study. 2020, 1 .

AMA Style

Thomas Theo Brehm, Dorothee Schwinge, Sibylle Lampalzer, Veronika Schlicker, Julia Kuechen, Michelle Thompson, Felix Ullrich, Samuel Huber, Stefan Schmiedel, Marylyn M Addo, Marc Luetgehetmann, Johannes K Knobloch, Julian Schulze Zur Wiesch, Ansgar W Lohse. High effectiveness of multimodal infection control interventions in preventing SARS-CoV-2 infections in healthcare professionals: a prospective longitudinal seroconversion study. . 2020; ():1.

Chicago/Turabian Style

Thomas Theo Brehm; Dorothee Schwinge; Sibylle Lampalzer; Veronika Schlicker; Julia Kuechen; Michelle Thompson; Felix Ullrich; Samuel Huber; Stefan Schmiedel; Marylyn M Addo; Marc Luetgehetmann; Johannes K Knobloch; Julian Schulze Zur Wiesch; Ansgar W Lohse. 2020. "High effectiveness of multimodal infection control interventions in preventing SARS-CoV-2 infections in healthcare professionals: a prospective longitudinal seroconversion study." , no. : 1.

Research article
Published: 28 May 2020 in Biotechnology Journal
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The Ebola virus (EBOV) can cause severe infections in humans, leading to a fatal outcome in a high percentage of cases. Neutralizing antibodies against the EBOV surface glycoprotein (GP) can prevent infections, demonstrating a straightforward way for an efficient vaccination strategy. Meanwhile, many different anti‐EBOV antibodies have been identified, whereas the exact binding epitopes are often unknown. Here, we present the analysis of serum samples from an EBOV vaccine trial with the viral vector vaccine rVSV‐ZEBOV and an Ebola virus disease (EVD) survivor, using high‐density peptide arrays. In this proof‐of‐principle study, we detected distinct IgG and IgM antibodies binding to different epitopes of EBOV GP: By mapping the whole GP as overlapping peptide fragments, we found new epitopes and confirmed epitopes from the literature. Furthermore, we could validate the highly selective binding epitope of a neutralizing monoclonal anti‐EBOV GP antibody. This shows that peptide arrays can be a valuable tool to study the humoral immune response to vaccines in patients and to support Ebola vaccine development. This article is protected by copyright. All rights reserved

ACS Style

Jasmin Heidepriem; Verena Krähling; Christine Dahlke; Timo Wolf; Florian Klein; Marylyn M. Addo; Stephan Becker; Felix F. Loeffler. Epitopes of Naturally Acquired and Vaccine‐Induced Anti‐Ebola Virus Glycoprotein Antibodies in Single Amino Acid Resolution. Biotechnology Journal 2020, 15, e2000069 .

AMA Style

Jasmin Heidepriem, Verena Krähling, Christine Dahlke, Timo Wolf, Florian Klein, Marylyn M. Addo, Stephan Becker, Felix F. Loeffler. Epitopes of Naturally Acquired and Vaccine‐Induced Anti‐Ebola Virus Glycoprotein Antibodies in Single Amino Acid Resolution. Biotechnology Journal. 2020; 15 (9):e2000069.

Chicago/Turabian Style

Jasmin Heidepriem; Verena Krähling; Christine Dahlke; Timo Wolf; Florian Klein; Marylyn M. Addo; Stephan Becker; Felix F. Loeffler. 2020. "Epitopes of Naturally Acquired and Vaccine‐Induced Anti‐Ebola Virus Glycoprotein Antibodies in Single Amino Acid Resolution." Biotechnology Journal 15, no. 9: e2000069.

Journal article
Published: 27 April 2020 in Travel Medicine and Infectious Disease
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Travelers’ diarrhea (TD) is the most common illness experienced by travelers to developing regions of the world and may be caused by bacterial, parasitic or viral pathogens. The available diagnostic tests include stool microscopy for protozoal infections, culture-dependent methods for bacterial infections and molecular methods for bacterial, parasitic and viral infections. We retrospectively evaluated demographic, clinical and microbiological data of patients presenting with TD at our travel clinic between 2009 and 2017. Among 676 patients with TD included in our study, at least one etiologic agent was found in only 21% (n = 145) of cases. In total, 195 enteropathogens were detected of which 110 were bacteria, 70 protozoa and 15 helminths. Bacterial infections were significantly more common when symptoms were present less than 14 days and travel duration did not exceed 30 days. Protozoa and helminths were predominantly detected in patients with longer lasting complaints. After stool culture was replaced by a multiplex-PCR gastrointestinal pathogen panel (GPP) at our center, significantly more intestinal bacterial pathogens were detected. Our results support an individualized approach in the diagnostic workup of patients with TD taking host and travel characteristics into account to avoid unnecessary diagnostic testing. Molecular culture-independent diagnostic stool tests provide better coverage of the variety of etiological agents than traditional stool culture and have the benefit of rapid detection. However, the high sensitivity bears challenges differentiating colonization from infection.

ACS Style

Thomas Theo Brehm; Marc Lütgehetmann; Egbert Tannich; Marylyn M. Addo; Ansgar W. Lohse; Thierry Rolling; Christof D. Vinnemeier. Risk factors for different intestinal pathogens among patients with traveler's diarrhea: A retrospective analysis at a German travel clinic (2009–2017). Travel Medicine and Infectious Disease 2020, 37, 101706 .

AMA Style

Thomas Theo Brehm, Marc Lütgehetmann, Egbert Tannich, Marylyn M. Addo, Ansgar W. Lohse, Thierry Rolling, Christof D. Vinnemeier. Risk factors for different intestinal pathogens among patients with traveler's diarrhea: A retrospective analysis at a German travel clinic (2009–2017). Travel Medicine and Infectious Disease. 2020; 37 ():101706.

Chicago/Turabian Style

Thomas Theo Brehm; Marc Lütgehetmann; Egbert Tannich; Marylyn M. Addo; Ansgar W. Lohse; Thierry Rolling; Christof D. Vinnemeier. 2020. "Risk factors for different intestinal pathogens among patients with traveler's diarrhea: A retrospective analysis at a German travel clinic (2009–2017)." Travel Medicine and Infectious Disease 37, no. : 101706.

Journal article
Published: 20 April 2020 in The Lancet Infectious Diseases
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Summary Background The Middle East respiratory syndrome coronavirus (MERS-CoV) causes a respiratory disease with a case fatality rate of up to 35%. Given its potential to cause a public health emergency and the absence of efficacious drugs or vaccines, MERS is one of the WHO priority diseases warranting urgent research and development of countermeasures. We aimed to assess safety and tolerability of an anti-MERS-CoV modified vaccinia virus Ankara (MVA)-based vaccine candidate that expresses the MERS-CoV spike glycoprotein, MVA-MERS-S, in healthy adults. Methods This open-label, phase 1 trial was done at the University Medical Center Hamburg-Eppendorf (Hamburg, Germany). Participants were healthy men and women aged 18–55 years with no clinically significant health problems as determined during medical history and physical examination, a body-mass index of 18·5–30·0 kg/m2 and weight of more than 50 kg at screening, and a negative pregnancy test for women. A key exclusion criterion was a previous MVA vaccination. For the prime immunisation, participants received doses of 1 × 107 plaque-forming unit (PFU; low-dose group) or 1 × 108 PFU (high-dose group) MVA-MERS-S intramuscularly. A second identical dose was administered intramuscularly as a booster immunisation 28 days after first injection. As a control group for immunogenicity analyses, blood samples were drawn at identical study timepoints from six healthy adults, who did not receive any injections. The primary objectives of the study were safety and tolerability of the two dosage levels and reactogenicity after administration. Immunogenicity was assessed as a secondary endpoint by ELISA and neutralisation tests. T-cell immunity was evaluated by interferon-γ-linked enzyme-linked immune absorbent spot assay. All participants who were vaccinated at least once were included in the safety analysis. Immunogenicity was analysed in the participants who completed 6 months of follow-up. This trial is registered with ClinicalTrials.gov, NCT03615911, and EudraCT, 2014-003195-23 Findings From Dec 17, 2017, to June 5, 2018, 26 participants (14 in the low-dose group and 12 in the high-dose group) were enrolled and received the first dose of the vaccine according to their group allocation. Of these, 23 participants (12 in the low-dose group and 11 in the high-dose group) received a second dose of MVA-MERS-S according to their group allocation after a 28-day interval and completed follow-up. Homologous prime–boost immunisation with MVA-MERS-S revealed a benign safety profile with only transient mild-to-moderate reactogenicity. Participants had no severe or serious adverse events. 67 vaccine-related adverse events were reported in ten (71%) of 14 participants in the low-dose group, and 111 were reported in ten (83%) of 12 participants in the high-dose group. Solicited local reactions were the most common adverse events: pain was observed in 17 (65%; seven in the low-dose group vs ten in the high-dose group) participants, swelling in ten (38%; two vs eight) participants, and induration in ten (38%; one vs nine) participants. Headaches (observed in seven participants in the low-dose group vs nine in the high-dose group) and fatigue or malaise (ten vs seven participants) were the most common solicited systemic adverse events. All adverse events resolved swiftly (within 1–3 days) and without sequelae. Following booster immunisation, nine (75%) of 12 participants in the low-dose group and 11 (100%) participants in the high-dose group showed seroconversion using a MERS-CoV S1 ELISA at any timepoint during the study. Binding antibody titres correlated with MERS-CoV-specific neutralising antibodies (Spearman's correlation r=0·86 [95% CI 0·6960–0·9427], p=0·0001). MERS-CoV spike-specific T-cell responses were detected in ten (83%) of 12 immunised participants in the low-dose group and ten (91%) of 11 immunised participants in the high-dose group. Interpretation Vaccination with MVA-MERS-S had a favourable safety profile without serious or severe adverse events. Homologous prime–boost immunisation induced humoral and cell-mediated responses against MERS-CoV. A dose–effect relationship was demonstrated for reactogenicity, but not for vaccine-induced immune responses. The data presented here support further clinical testing of MVA-MERS-S in larger cohorts to advance MERS vaccine development. Funding German Center for Infection Research.

ACS Style

Till Koch; Christine Dahlke; Anahita Fathi; Alexandra Kupke; Verena Krähling; Nisreen Okba; Sandro Halwe; Cornelius Rohde; Markus Eickmann; Asisa Volz; Thomas Hesterkamp; Alen Jambrecina; Saskia Borregaard; My L Ly; Madeleine E Zinser; Etienne Bartels; Joseph S H Poetsch; Reza Neumann; Robert Fux; Stefan Schmiedel; Ansgar W Lohse; Bart L Haagmans; Gerd Sutter; Stephan Becker; Marylyn M Addo. Safety and immunogenicity of a modified vaccinia virus Ankara vector vaccine candidate for Middle East respiratory syndrome: an open-label, phase 1 trial. The Lancet Infectious Diseases 2020, 20, 827 -838.

AMA Style

Till Koch, Christine Dahlke, Anahita Fathi, Alexandra Kupke, Verena Krähling, Nisreen Okba, Sandro Halwe, Cornelius Rohde, Markus Eickmann, Asisa Volz, Thomas Hesterkamp, Alen Jambrecina, Saskia Borregaard, My L Ly, Madeleine E Zinser, Etienne Bartels, Joseph S H Poetsch, Reza Neumann, Robert Fux, Stefan Schmiedel, Ansgar W Lohse, Bart L Haagmans, Gerd Sutter, Stephan Becker, Marylyn M Addo. Safety and immunogenicity of a modified vaccinia virus Ankara vector vaccine candidate for Middle East respiratory syndrome: an open-label, phase 1 trial. The Lancet Infectious Diseases. 2020; 20 (7):827-838.

Chicago/Turabian Style

Till Koch; Christine Dahlke; Anahita Fathi; Alexandra Kupke; Verena Krähling; Nisreen Okba; Sandro Halwe; Cornelius Rohde; Markus Eickmann; Asisa Volz; Thomas Hesterkamp; Alen Jambrecina; Saskia Borregaard; My L Ly; Madeleine E Zinser; Etienne Bartels; Joseph S H Poetsch; Reza Neumann; Robert Fux; Stefan Schmiedel; Ansgar W Lohse; Bart L Haagmans; Gerd Sutter; Stephan Becker; Marylyn M Addo. 2020. "Safety and immunogenicity of a modified vaccinia virus Ankara vector vaccine candidate for Middle East respiratory syndrome: an open-label, phase 1 trial." The Lancet Infectious Diseases 20, no. 7: 827-838.

Journal article
Published: 20 April 2020 in The Lancet Infectious Diseases
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Till Koch; Christine Dahlke; Anahita Fathi; Alexandra Kupke; Verena Krähling; Nisreen M A Okba; Sandro Halwe; Cornelius Rohde; Markus Eickmann; Asisa Volz; Thomas Hesterkamp; Alen Jambrecina; Saskia Borregaard; My L Ly; Madeleine E Zinser; Etienne Bartels; Joseph S H Poetsch; Reza Neumann; Robert Fux; Stefan Schmiedel; Ansgar W Lohse; Bart L Haagmans; Gerd Sutter; Stephan Becker; Marylyn M Addo. Safety and immunogenicity of a modified vaccinia virus Ankara vector vaccine candidate for Middle East respiratory syndrome: an open-label, phase 1 trial. The Lancet Infectious Diseases 2020, 1 .

AMA Style

Till Koch, Christine Dahlke, Anahita Fathi, Alexandra Kupke, Verena Krähling, Nisreen M A Okba, Sandro Halwe, Cornelius Rohde, Markus Eickmann, Asisa Volz, Thomas Hesterkamp, Alen Jambrecina, Saskia Borregaard, My L Ly, Madeleine E Zinser, Etienne Bartels, Joseph S H Poetsch, Reza Neumann, Robert Fux, Stefan Schmiedel, Ansgar W Lohse, Bart L Haagmans, Gerd Sutter, Stephan Becker, Marylyn M Addo. Safety and immunogenicity of a modified vaccinia virus Ankara vector vaccine candidate for Middle East respiratory syndrome: an open-label, phase 1 trial. The Lancet Infectious Diseases. 2020; ():1.

Chicago/Turabian Style

Till Koch; Christine Dahlke; Anahita Fathi; Alexandra Kupke; Verena Krähling; Nisreen M A Okba; Sandro Halwe; Cornelius Rohde; Markus Eickmann; Asisa Volz; Thomas Hesterkamp; Alen Jambrecina; Saskia Borregaard; My L Ly; Madeleine E Zinser; Etienne Bartels; Joseph S H Poetsch; Reza Neumann; Robert Fux; Stefan Schmiedel; Ansgar W Lohse; Bart L Haagmans; Gerd Sutter; Stephan Becker; Marylyn M Addo. 2020. "Safety and immunogenicity of a modified vaccinia virus Ankara vector vaccine candidate for Middle East respiratory syndrome: an open-label, phase 1 trial." The Lancet Infectious Diseases , no. : 1.

Other
Published: 17 April 2020
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SARS-CoV-2 is the causative agent of COVID-19 and is a severe threat to global health. Patients infected with SARS-CoV-2 show a wide range of symptoms and disease severity, while limited data is available on its immunogenicity. Here, the kinetics of the development of SARS-CoV-2-specific antibody responses in relation to clinical features and dynamics of specific B-cell populations are reported. Immunophenotyping of B cells was performed by flow cytometry with longitudinally collected PBMCs. In parallel, serum samples were analyzed for the presence of SARS-CoV-2-specific IgA, IgG, and IgM antibodies using whole proteome peptide microarrays. Soon after disease onset in a mild case, we observed an increased frequency of plasmablasts concomitantly with a strong SARS-CoV-2-specific IgA response. In contrast, a case with more severe progression showed a delayed, but eventually very strong and broad SARS-CoV-2-specific IgA response. This case study shows that determining SARS-CoV-2-specific antibody epitopes can be valuable to monitor the specificity and magnitude of the early B-cell response, which could guide the development of vaccine candidates. Follow-up studies are required to evaluate whether the kinetics and strength of the SARS-CoV-2-specific IgA response could be potential prognostic markers of viral control.

ACS Style

Christine Dahlke; Jasmin Heidepriem; Robin Kobbe; Rene Santer; Till Koch; Anahita Fathi; My L. Ly; Stefan Schmiedel; Peter H. Seeberger; ID-UKE COVID-19 study group; Marylyn M. Addo; Felix F. Loeffler. Distinct early IgA profile may determine severity of COVID-19 symptoms: an immunological case series. 2020, 1 .

AMA Style

Christine Dahlke, Jasmin Heidepriem, Robin Kobbe, Rene Santer, Till Koch, Anahita Fathi, My L. Ly, Stefan Schmiedel, Peter H. Seeberger, ID-UKE COVID-19 study group, Marylyn M. Addo, Felix F. Loeffler. Distinct early IgA profile may determine severity of COVID-19 symptoms: an immunological case series. . 2020; ():1.

Chicago/Turabian Style

Christine Dahlke; Jasmin Heidepriem; Robin Kobbe; Rene Santer; Till Koch; Anahita Fathi; My L. Ly; Stefan Schmiedel; Peter H. Seeberger; ID-UKE COVID-19 study group; Marylyn M. Addo; Felix F. Loeffler. 2020. "Distinct early IgA profile may determine severity of COVID-19 symptoms: an immunological case series." , no. : 1.

Journal article
Published: 23 March 2020 in Vaccines
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Ebola virus epidemics can be effectively limited by the VSV-EBOV vaccine (Ervebo) due to its rapid protection abilities; however, side effects prevent the broad use of VSV-EBOV as vaccine. Mechanisms explaining the efficient immune activation after single injection with the VSV-EBOV vaccine remain mainly unknown. Here, using the clinically available VSV-EBOV vaccine (Ervebo), we show that the cell-intrinsic expression of the interferon-inhibitor Usp18 in CD169+ macrophages is one important factor modulating the anti-Ebola virus immune response. The absence of Usp18 in CD169+ macrophages led to the reduced local replication of VSV-EBOV followed by a diminished innate as well as adaptive immune response. In line, CD169-Cre+/ki x Usp18fl/fl mice showed reduced innate and adaptive immune responses against the VSV wildtype strain and died quickly after infection, suggesting that a lack of Usp18 makes mice more susceptible to the side effects of the VSV vector. In conclusion, our study shows that Usp18 expression in CD169+ macrophages is one important surrogate marker for effective vaccination against VSV-EBOV, and probably other VSV-based vaccines also.

ACS Style

Sarah-Kim Friedrich; Rosa Schmitz; Michael Bergerhausen; Judith Lang; Lamin B. Cham; Vikas Duhan; Dieter Häussinger; Cornelia Hardt; Marylyn Addo; Marco Prinz; Kenichi Asano; Philipp Alexander Lang; Karl Sebastian Lang. Usp18 Expression in CD169+ Macrophages is Important for Strong Immune Response after Vaccination with VSV-EBOV. Vaccines 2020, 8, 142 .

AMA Style

Sarah-Kim Friedrich, Rosa Schmitz, Michael Bergerhausen, Judith Lang, Lamin B. Cham, Vikas Duhan, Dieter Häussinger, Cornelia Hardt, Marylyn Addo, Marco Prinz, Kenichi Asano, Philipp Alexander Lang, Karl Sebastian Lang. Usp18 Expression in CD169+ Macrophages is Important for Strong Immune Response after Vaccination with VSV-EBOV. Vaccines. 2020; 8 (1):142.

Chicago/Turabian Style

Sarah-Kim Friedrich; Rosa Schmitz; Michael Bergerhausen; Judith Lang; Lamin B. Cham; Vikas Duhan; Dieter Häussinger; Cornelia Hardt; Marylyn Addo; Marco Prinz; Kenichi Asano; Philipp Alexander Lang; Karl Sebastian Lang. 2020. "Usp18 Expression in CD169+ Macrophages is Important for Strong Immune Response after Vaccination with VSV-EBOV." Vaccines 8, no. 1: 142.

Letter
Published: 05 September 2019 in Human Vaccines & Immunotherapeutics
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The devastating Ebola virus (EBOV) outbreak in West Africa in 2013-2016 has flagged the need for the timely development of vaccines for high-threat pathogens. To be better prepared for new epidemics, the WHO has compiled a list of priority pathogens that are likely to cause future outbreaks and for which R&D efforts are, therefore, paramount (R&D Blueprint: https://www.who.int/blueprint/priority-diseases/en/ ). To this end, the detailed characterization of vaccine platforms is needed. The vesicular stomatitis virus (VSV) has been established as a robust vaccine vector backbone for infectious diseases for well over a decade. The recent clinical trials testing the vaccine candidate VSV-EBOV against EBOV disease now have added a substantial amount of clinical data and suggest VSV to be an ideal vaccine vector candidate for outbreak pathogens. In this review, we discuss insights gained from the clinical VSV-EBOV vaccine trials as well as from animal studies investigating vaccine candidates for Blueprint pathogens.

ACS Style

Anahita Fathi; Christine Dahlke; Marylyn Addo. Recombinant vesicular stomatitis virus vector vaccines for WHO blueprint priority pathogens. Human Vaccines & Immunotherapeutics 2019, 15, 2269 -2285.

AMA Style

Anahita Fathi, Christine Dahlke, Marylyn Addo. Recombinant vesicular stomatitis virus vector vaccines for WHO blueprint priority pathogens. Human Vaccines & Immunotherapeutics. 2019; 15 (10):2269-2285.

Chicago/Turabian Style

Anahita Fathi; Christine Dahlke; Marylyn Addo. 2019. "Recombinant vesicular stomatitis virus vector vaccines for WHO blueprint priority pathogens." Human Vaccines & Immunotherapeutics 15, no. 10: 2269-2285.