This page has only limited features, please log in for full access.
In this longitudinal cohort study, we assessed the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) seroconversion rates and analyzed the coronavirus disease 2019 (COVID-19) vaccine-induced immunity of 872 hospital workers at the University Medical Center Hamburg-Eppendorf between May 11 and May 31, 2021. The overall seroprevalence of anti-NC-SARS-CoV-2 antibodies was 4.7% (n=41), indicating low SARS-CoV-2 infection rates and persistent effectiveness of hospital-wide infection control interventions during the second and third wave of the pandemic. In total, 92.7% (n=808) out of the entire study cohort, 98.2% (n=325) of those who had been vaccinated once and all 393 individuals who had been vaccinated twice had detectable anti-S1-RBD-SARS-CoV-2 antibody titers and no significant differences in vaccine-induced immune response were detected between male and female individuals and between different age groups. Vaccinated study participants with detectable anti-NC-SARS-CoV-2 antibody titers (n=30) developed generally higher anti-S1-RBD-SARS-CoV-2 antibody titers compared to anti-NC-SARS-CoV-2 negative individuals (n=694) (median titer: 7812 vs. 345 BAU/ml, p<0.0001). Furthermore, study participants who received heterologous vaccination with AZD1222 followed by an mRNA vaccine showed markedly higher anti-S1-RBD-SARS-CoV-2 antibody titers than individuals who received two doses of an mRNA vaccine or two doses of AZD1222 (median titer: AZD1222 / AZD1222: 1069 BAU/ml, mRNA / mRNA: 1388 BAU/ml, AZD1222/mRNA: 9450 BAU/ml; p<0.0001). Our results demonstrate that infection control interventions were generally effective in preventing nosocomial transmission of SARS-CoV-2 and that COVID-19 vaccines can elicit strong humoral responses in the majority of a real-world cohort of hospital workers.
Thomas Theo Brehm; Michelle Thompson; Felix Ullrich; Dorothee Schwinge; Marylyn M Addo; Anthea Spier; Johannes K Knobloch; Martin Aepfelbacher; Ansgar W Lohse; Marc Lütgehetmann; Julian Schulze Zur Wiesch. Low SARS-CoV-2 infection rate and high vaccine-induced immunity among German healthcare workers at the end of the third wave of the COVID-19 pandemic. 2021, 1 .
AMA StyleThomas Theo Brehm, Michelle Thompson, Felix Ullrich, Dorothee Schwinge, Marylyn M Addo, Anthea Spier, Johannes K Knobloch, Martin Aepfelbacher, Ansgar W Lohse, Marc Lütgehetmann, Julian Schulze Zur Wiesch. Low SARS-CoV-2 infection rate and high vaccine-induced immunity among German healthcare workers at the end of the third wave of the COVID-19 pandemic. . 2021; ():1.
Chicago/Turabian StyleThomas Theo Brehm; Michelle Thompson; Felix Ullrich; Dorothee Schwinge; Marylyn M Addo; Anthea Spier; Johannes K Knobloch; Martin Aepfelbacher; Ansgar W Lohse; Marc Lütgehetmann; Julian Schulze Zur Wiesch. 2021. "Low SARS-CoV-2 infection rate and high vaccine-induced immunity among German healthcare workers at the end of the third wave of the COVID-19 pandemic." , no. : 1.
Few data are available regarding the efficacy of anti-SARS-CoV-2 vaccines in patients with hematological malignancies, and particular, plasma cell neoplasia. This ongoing single-center study aimed to describe the level of post-vaccination anti-SARS-CoV-2-antibodies depending on B lymphocyte count, current therapy, and remission status of patients with multiple myeloma and related plasma cell dyscrasia, after the first dose of anti-SARS-CoV-2 vaccination. The 82 patients included in this study received SARS-CoV-2 vaccines (including mRNA- and vector-based vaccines) as a routine measure. After the first vaccination, a positive SARS-CoV-2 spike protein antibody titer (SP-AbT) was detected in 23% of assessable patients. SARS-CoV-2 SP-AbT was significantly higher in patients with higher CD19+ B lymphocyte counts. A cut-off value of ≥30 CD19+ B cells/µL was significantly positive correlating with higher SARS-CoV-2 SP-AbT. In contrast, current treatment with anti-CD38-antibodies has led to significantly reduced SP-AbT titers. Furthermore, in multivariable linear regression, higher age and insufficiently controlled disease significantly correlated negatively with SARS-CoV-2 SP-AbT. Conversely, treatment with immunomodulatory drugs did not harm the development of antibody titers. Based on our results, the majority of myeloma patients respond poorly after receiving the first dose of any anti-SARS-CoV-2 vaccination and need booster vaccination.
Susanne Ghandili; Martin Schönlein; Marc Lütgehetmann; Julian Schulze Zur Wiesch; Heiko Becher; Carsten Bokemeyer; Marianne Sinn; Katja Weisel; Lisa Leypoldt. Post-Vaccination Anti-SARS-CoV-2-Antibody Response in Patients with Multiple Myeloma Correlates with Low CD19+ B-Lymphocyte Count and Anti-CD38 Treatment. Cancers 2021, 13, 3800 .
AMA StyleSusanne Ghandili, Martin Schönlein, Marc Lütgehetmann, Julian Schulze Zur Wiesch, Heiko Becher, Carsten Bokemeyer, Marianne Sinn, Katja Weisel, Lisa Leypoldt. Post-Vaccination Anti-SARS-CoV-2-Antibody Response in Patients with Multiple Myeloma Correlates with Low CD19+ B-Lymphocyte Count and Anti-CD38 Treatment. Cancers. 2021; 13 (15):3800.
Chicago/Turabian StyleSusanne Ghandili; Martin Schönlein; Marc Lütgehetmann; Julian Schulze Zur Wiesch; Heiko Becher; Carsten Bokemeyer; Marianne Sinn; Katja Weisel; Lisa Leypoldt. 2021. "Post-Vaccination Anti-SARS-CoV-2-Antibody Response in Patients with Multiple Myeloma Correlates with Low CD19+ B-Lymphocyte Count and Anti-CD38 Treatment." Cancers 13, no. 15: 3800.
Summary COVID-19 is a respiratory tract infection that can affect multiple organ systems. Predicting the severity and clinical outcome of individual patients is a major unmet clinical need that remains challenging due to intra- and inter-patient variability. Here, we longitudinally profiled and integrated more than 150 clinical, laboratory, and immunological parameters of 173 patients with mild to fatal COVID-19. Using systems biology, we detected progressive dysregulation of multiple parameters indicative of organ damage that correlated with disease severity, particularly affecting kidneys, hepatobiliary system, and immune landscape. By performing unsupervised clustering and trajectory analysis, we identified T and B cell depletion as early indicators of a complicated disease course. In addition, markers of hepatobiliary damage emerged as robust predictor of lethal outcome in critically ill patients. This allowed us to propose a novel clinical COVID-19 SeveriTy (COST) score that distinguishes complicated disease trajectories and predicts lethal outcome in critically ill patients.
Marcel S. Woo; Friedrich Haag; Axel Nierhaus; Dominik Jarczak; Kevin Roedl; Christina Mayer; Thomas T. Brehm; Marc van der Meirschen; Annette Hennigs; Maximilian Christopeit; Walter Fiedler; Panagiotis Karagiannis; Christoph Burdelski; Alexander Schultze; Samuel Huber; Marylyn M. Addo; Stefan Schmiedel; Manuel A. Friese; Stefan Kluge; Julian Schulze Zur Wiesch. Multi-dimensional and longitudinal systems profiling reveals predictive pattern of severe COVID-19. iScience 2021, 24, 102752 .
AMA StyleMarcel S. Woo, Friedrich Haag, Axel Nierhaus, Dominik Jarczak, Kevin Roedl, Christina Mayer, Thomas T. Brehm, Marc van der Meirschen, Annette Hennigs, Maximilian Christopeit, Walter Fiedler, Panagiotis Karagiannis, Christoph Burdelski, Alexander Schultze, Samuel Huber, Marylyn M. Addo, Stefan Schmiedel, Manuel A. Friese, Stefan Kluge, Julian Schulze Zur Wiesch. Multi-dimensional and longitudinal systems profiling reveals predictive pattern of severe COVID-19. iScience. 2021; 24 (7):102752.
Chicago/Turabian StyleMarcel S. Woo; Friedrich Haag; Axel Nierhaus; Dominik Jarczak; Kevin Roedl; Christina Mayer; Thomas T. Brehm; Marc van der Meirschen; Annette Hennigs; Maximilian Christopeit; Walter Fiedler; Panagiotis Karagiannis; Christoph Burdelski; Alexander Schultze; Samuel Huber; Marylyn M. Addo; Stefan Schmiedel; Manuel A. Friese; Stefan Kluge; Julian Schulze Zur Wiesch. 2021. "Multi-dimensional and longitudinal systems profiling reveals predictive pattern of severe COVID-19." iScience 24, no. 7: 102752.
Skeletal muscle wasting is commonly associated with chronic kidney disease (CKD), resulting in increased morbidity and mortality. However, the link between kidney and muscle function remains poorly understood. Here, we took a complementary interorgan approach to investigate skeletal muscle wasting in CKD. We identified increased production and elevated blood levels of soluble pro-cachectic factors, including activin A, directly linking experimental and human CKD to skeletal muscle wasting programs. Single-cell sequencing data identified the expression of activin A in specific kidney cell populations of fibroblasts and cells of the juxtaglomerular apparatus. We propose that persistent and increased kidney production of pro-cachectic factors, combined with a lack of kidney clearance, facilitates a vicious kidney/muscle signaling cycle, leading to exacerbated blood accumulation and, thereby, skeletal muscle wasting. Systemic pharmacological blockade of activin A using soluble activin receptor type IIB ligand trap as well as muscle-specific adeno-associated virus-mediated downregulation of its receptor ACVR2A/B prevented muscle wasting in different mouse models of experimental CKD, suggesting that activin A is a key factor in CKD-induced cachexia. In summary, we uncovered a crosstalk between kidney and muscle and propose modulation of activin signaling as a potential therapeutic strategy for skeletal muscle wasting in CKD.
Francesca Solagna; Caterina Tezze; Maja T. Lindenmeyer; Shun Lu; Guochao Wu; Shuya Liu; Yu Zhao; Robert Mitchell; Charlotte Meyer; Saleh Omairi; Temel Kilic; Andrea Paolini; Olli Ritvos; Arja Pasternack; Antonios Matsakas; Dominik Kylies; Julian Schulze Zur Wiesch; Jan-Eric Turner; Nicola Wanner; Viji Nair; Felix Eichinger; Rajasree Menon; Ina V. Martin; Barbara M. Klinkhammer; Elion Hoxha; Clemens D. Cohen; Pierre-Louis Tharaux; Peter Boor; Tammo Ostendorf; Matthias Kretzler; Marco Sandri; Oliver Kretz; Victor G. Puelles; Ketan Patel; Tobias B. Huber. Pro-cachectic factors link experimental and human chronic kidney disease to skeletal muscle wasting programs. Journal of Clinical Investigation 2021, 131, 1 .
AMA StyleFrancesca Solagna, Caterina Tezze, Maja T. Lindenmeyer, Shun Lu, Guochao Wu, Shuya Liu, Yu Zhao, Robert Mitchell, Charlotte Meyer, Saleh Omairi, Temel Kilic, Andrea Paolini, Olli Ritvos, Arja Pasternack, Antonios Matsakas, Dominik Kylies, Julian Schulze Zur Wiesch, Jan-Eric Turner, Nicola Wanner, Viji Nair, Felix Eichinger, Rajasree Menon, Ina V. Martin, Barbara M. Klinkhammer, Elion Hoxha, Clemens D. Cohen, Pierre-Louis Tharaux, Peter Boor, Tammo Ostendorf, Matthias Kretzler, Marco Sandri, Oliver Kretz, Victor G. Puelles, Ketan Patel, Tobias B. Huber. Pro-cachectic factors link experimental and human chronic kidney disease to skeletal muscle wasting programs. Journal of Clinical Investigation. 2021; 131 (11):1.
Chicago/Turabian StyleFrancesca Solagna; Caterina Tezze; Maja T. Lindenmeyer; Shun Lu; Guochao Wu; Shuya Liu; Yu Zhao; Robert Mitchell; Charlotte Meyer; Saleh Omairi; Temel Kilic; Andrea Paolini; Olli Ritvos; Arja Pasternack; Antonios Matsakas; Dominik Kylies; Julian Schulze Zur Wiesch; Jan-Eric Turner; Nicola Wanner; Viji Nair; Felix Eichinger; Rajasree Menon; Ina V. Martin; Barbara M. Klinkhammer; Elion Hoxha; Clemens D. Cohen; Pierre-Louis Tharaux; Peter Boor; Tammo Ostendorf; Matthias Kretzler; Marco Sandri; Oliver Kretz; Victor G. Puelles; Ketan Patel; Tobias B. Huber. 2021. "Pro-cachectic factors link experimental and human chronic kidney disease to skeletal muscle wasting programs." Journal of Clinical Investigation 131, no. 11: 1.
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.
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 StyleThomas 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 StyleThomas 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.
Background: The prevalence of metabolic and cardiovascular diseases is rising worldwide. However, little is known about the impact of such disorders on hepatic disease progression in chronic hepatitis B (CHB) during the era of potent nucleo(s)tide analogues (NAs). Methods: We retrospectively analyzed a single-center cohort of 602 CHB patients, comparing the frequency of liver cirrhosis at baseline and incidences of liver-related events during follow-up (hepatocellular carcinoma, liver transplantation and liver-related death) between CHB patients with a history of diabetes, obesity, hypertension or coronary heart disease (CHD). Results: Rates of cirrhosis at baseline and liver-related events during follow-up (median follow-up time: 2.51 years; NA-treated: 37%) were substantially higher in CHB patients with diabetes (11/23; 3/23), obesity (6/13; 2/13), CHD (7/11; 2/11) or hypertension (15/43; 4/43) compared to CHB patients without the indicated comorbidities (26/509; 6/509). Multivariate analysis identified diabetes as the most significant predictor for cirrhosis (p = 0.0105), while comorbidities did not correlate with liver-related events in pre-existing cirrhosis. Conclusion: The combination of metabolic diseases and CHB is associated with substantially increased rates of liver cirrhosis and secondary liver-related events compared to CHB alone, indicating that hepatitis B patients with metabolic comorbidities warrant particular attention in disease surveillance and evaluation of treatment indication.
Jan-Hendrik Bockmann; Matin Kohsar; John Murray; Vanessa Hamed; Maura Dandri; Stefan Lüth; Ansgar Lohse; Julian Schulze-Zur-Wiesch. High Rates of Liver Cirrhosis and Hepatocellular Carcinoma in Chronic Hepatitis B Patients with Metabolic and Cardiovascular Comorbidities. Microorganisms 2021, 9, 968 .
AMA StyleJan-Hendrik Bockmann, Matin Kohsar, John Murray, Vanessa Hamed, Maura Dandri, Stefan Lüth, Ansgar Lohse, Julian Schulze-Zur-Wiesch. High Rates of Liver Cirrhosis and Hepatocellular Carcinoma in Chronic Hepatitis B Patients with Metabolic and Cardiovascular Comorbidities. Microorganisms. 2021; 9 (5):968.
Chicago/Turabian StyleJan-Hendrik Bockmann; Matin Kohsar; John Murray; Vanessa Hamed; Maura Dandri; Stefan Lüth; Ansgar Lohse; Julian Schulze-Zur-Wiesch. 2021. "High Rates of Liver Cirrhosis and Hepatocellular Carcinoma in Chronic Hepatitis B Patients with Metabolic and Cardiovascular Comorbidities." Microorganisms 9, no. 5: 968.
Hepatitis D virus (HDV) is a small, defective RNA virus that requires the hepatitis B surface antigen (HBsAg) of the hepatitis B virus (HBV) for its assembly, release, and transmission. Chronic HBV/HDV infection often has a severe clinical outcome and is difficult to treat. The important role of a robust virus-specific T cell response for natural viral control has been established for many other chronic viral infections, but the exact role of the T cell response in the control and progression of chronic HDV infection is far less clear. Several recent studies have characterized HDV-specific CD4+ and CD8+ T cell response on a peptide level. This review comprehensively summarizes all HDV-specific T cell epitopes described to date and describes our current knowledge of the role of T cells in HDV infection. While we now have better tools to study the adaptive anti-HDV-specific T cell response, further efforts are needed to define the HLA restriction of additional HDV-specific T cell epitopes, establish additional HDV-specific MHC tetramers, understand the degree of cross HDV genotype reactivity of individual epitopes and understand the correlation of the HBV and HDV-specific T cell response as well as the breadth and specificity of the intrahepatic HDV-specific T cell response.
Matin Kohsar; Johanna Landahl; Christoph Neumann-Haefelin; Julian Schulze Zur Wiesch. Human hepatitis D virus-specific T cell epitopes. JHEP Reports 2021, 3, 100294 .
AMA StyleMatin Kohsar, Johanna Landahl, Christoph Neumann-Haefelin, Julian Schulze Zur Wiesch. Human hepatitis D virus-specific T cell epitopes. JHEP Reports. 2021; 3 (4):100294.
Chicago/Turabian StyleMatin Kohsar; Johanna Landahl; Christoph Neumann-Haefelin; Julian Schulze Zur Wiesch. 2021. "Human hepatitis D virus-specific T cell epitopes." JHEP Reports 3, no. 4: 100294.
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.
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 StyleJohannes 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 StyleJohannes 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.
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.
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 StyleThomas 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 StyleThomas 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.
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.
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 StyleJohannes 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 StyleJohannes 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.
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.
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 StyleYu 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 StyleYu 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.
In patients with hepatitis E virus (HEV) infections, extrahepatic, particularly renal and hematological manifestations, are increasingly reported in the medical literature but have never been studied compared to a control cohort. We retrospectively analyzed medical records of consecutive patients that were diagnosed with acute hepatitis E (AHE) (n = 69) or acute hepatitis A (AHA) (n = 46) at the University Medical Center Hamburg Eppendorf from January 2009 to August 2019 for demographical, clinical, and laboratory information. Patients with AHE had significantly lower median levels of ALAT (798 U/L) and total bilirubin (1.8 mg/dL) compared to patients with AHA (2326 U/L; p < 0.001 and 5.2 mg/dL; p < 0.001), suggesting a generally less severe hepatitis. In contrast, patients with AHE had significantly higher median serum creatinine levels (0.9 mg/dL vs. 0.8 mg/dL; p = 0.002) and lower median estimated glomerular filtration rate (eGFR) (91 mL/min/1.73 m2 vs. 109 mL/min/1.73 m2; p < 0.001) than patients with AHA. Leucocyte, neutrophil and lymphocyte count, hemoglobin, platelets, red cell distribution width (RDW), neutrophil to lymphocyte ratio (NLR), and RDW to lymphocyte ratio (RLR) did not differ between patients with AHE and those with AHA. Our observations indicate that renal but not hematological interference presents an underrecognized extrahepatic feature of AHE, while inflammation of the liver seems to be more severe in AHA.
Thomas Theo Brehm; Omid Mazaheri; Thomas Horvatits; Marc Lütgehetmann; Julian Schulze Zur Wiesch; Ansgar W. Lohse; Susanne Polywka; Sven Pischke. Lower Levels of Transaminases but Higher Levels of Serum Creatinine in Patients with Acute Hepatitis E in Comparison to Patients with Hepatitis A. Pathogens 2021, 10, 60 .
AMA StyleThomas Theo Brehm, Omid Mazaheri, Thomas Horvatits, Marc Lütgehetmann, Julian Schulze Zur Wiesch, Ansgar W. Lohse, Susanne Polywka, Sven Pischke. Lower Levels of Transaminases but Higher Levels of Serum Creatinine in Patients with Acute Hepatitis E in Comparison to Patients with Hepatitis A. Pathogens. 2021; 10 (1):60.
Chicago/Turabian StyleThomas Theo Brehm; Omid Mazaheri; Thomas Horvatits; Marc Lütgehetmann; Julian Schulze Zur Wiesch; Ansgar W. Lohse; Susanne Polywka; Sven Pischke. 2021. "Lower Levels of Transaminases but Higher Levels of Serum Creatinine in Patients with Acute Hepatitis E in Comparison to Patients with Hepatitis A." Pathogens 10, no. 1: 60.
B cells play a central role in antiviral and antiparasitic immunity, not only as producers of antibodies, but also as APCs and mediators of inflammation. In this study, we used 16‐color flow cytometry analysis to investigate the frequency, differentiation, and activation status of peripheral B cells of patients with SARS‐CoV‐2 infection or acute Plasmodium falciparum malaria compared with the healthy individuals. As a main result, we observed an increase of the frequency of (CD27–, CD21–) atypical memory B cells and (CD19+, CD27+, CD38+) plasmablasts in malaria and COVID‐19 patients. Additionally, CD86, PD‐1, CXCR3, and CD39 expression was up‐regulated, whereas CD73 was down‐regulated on plasmablasts of COVID‐19 and malaria patients compared with the bulk B cell population. In particular, there was a more pronounced loss of CD73+ B cells in malaria. The frequency of plasmablasts positively correlated with serum levels of CRP, IL‐6, and LDH of COVID‐19 patients. In the longitudinal course of COVID‐19, a rapid normalization of the frequency of atypical memory B cells was observed. The role and function of plasmablasts and atypical memory B cells in COVID‐19 and other acute infections remain to be further investigated. The role of B cells as either “driver or passenger” of hyperinflammation during COVID‐19 needs to be clarified.
Nils H. Wildner; Parimah Ahmadi; Sophia Schulte; Franziska Brauneck; Matin Kohsar; Marc Lütgehetmann; Claudia Beisel; Marylyn M. Addo; Friedrich Haag; Julian Schulze Zur Wiesch. B cell analysis in SARS‐CoV‐2 versus malaria: Increased frequencies of plasmablasts and atypical memory B cells in COVID‐19. Journal of Leukocyte Biology 2020, 109, 77 -90.
AMA StyleNils H. Wildner, Parimah Ahmadi, Sophia Schulte, Franziska Brauneck, Matin Kohsar, Marc Lütgehetmann, Claudia Beisel, Marylyn M. Addo, Friedrich Haag, Julian Schulze Zur Wiesch. B cell analysis in SARS‐CoV‐2 versus malaria: Increased frequencies of plasmablasts and atypical memory B cells in COVID‐19. Journal of Leukocyte Biology. 2020; 109 (1):77-90.
Chicago/Turabian StyleNils H. Wildner; Parimah Ahmadi; Sophia Schulte; Franziska Brauneck; Matin Kohsar; Marc Lütgehetmann; Claudia Beisel; Marylyn M. Addo; Friedrich Haag; Julian Schulze Zur Wiesch. 2020. "B cell analysis in SARS‐CoV‐2 versus malaria: Increased frequencies of plasmablasts and atypical memory B cells in COVID‐19." Journal of Leukocyte Biology 109, no. 1: 77-90.
We provide detailed clinical, virological, and immunological data of a B-cell–depleted patient treated with obinutuzumab for follicular lymphoma with protracted coronavirus disease 2019 (COVID-19) and viremia. A sustained response was achieved after 2 courses of remdesivir and subsequent convalescent plasma therapy. Immunocompromised patients might require combined and prolonged antiviral treatment regimens.
Jakob Malsy; Luzia Veletzky; Janna Heide; Annette Hennigs; Ines Gil-Ibanez; Alexander Stein; Marc Lütgehetmann; Ulrich Rosien; Dorothea Jasper; Sven Peine; Jens Hiller; Friedrich Haag; Stefan Schmiedel; Samuel Huber; Sabine Jordan; Marylyn M Addo; Julian Schulze Zur Wiesch. Sustained Response After Remdesivir and Convalescent Plasma Therapy in a B-Cell–Depleted Patient With Protracted Coronavirus Disease 2019 (COVID-19). Clinical Infectious Diseases 2020, 1 .
AMA StyleJakob Malsy, Luzia Veletzky, Janna Heide, Annette Hennigs, Ines Gil-Ibanez, Alexander Stein, Marc Lütgehetmann, Ulrich Rosien, Dorothea Jasper, Sven Peine, Jens Hiller, Friedrich Haag, Stefan Schmiedel, Samuel Huber, Sabine Jordan, Marylyn M Addo, Julian Schulze Zur Wiesch. Sustained Response After Remdesivir and Convalescent Plasma Therapy in a B-Cell–Depleted Patient With Protracted Coronavirus Disease 2019 (COVID-19). Clinical Infectious Diseases. 2020; ():1.
Chicago/Turabian StyleJakob Malsy; Luzia Veletzky; Janna Heide; Annette Hennigs; Ines Gil-Ibanez; Alexander Stein; Marc Lütgehetmann; Ulrich Rosien; Dorothea Jasper; Sven Peine; Jens Hiller; Friedrich Haag; Stefan Schmiedel; Samuel Huber; Sabine Jordan; Marylyn M Addo; Julian Schulze Zur Wiesch. 2020. "Sustained Response After Remdesivir and Convalescent Plasma Therapy in a B-Cell–Depleted Patient With Protracted Coronavirus Disease 2019 (COVID-19)." Clinical Infectious Diseases , no. : 1.
The ectoenzymes CD39 and CD73 play a major role in controlling tissue inflammation by regulating the balance between adenosine triphosphate (ATP) and adenosine. Still, little is known about the role of these two enzymes and ATP and its metabolites in the pathophysiology of inflammatory bowel disease (IBD). We isolated mononuclear cells from peripheral blood and lamina propria of the large intestine of patients diagnosed with IBD and of healthy volunteers. We then comprehensively analyzed the CD39 and CD73 expression patterns together with markers of activation (HLA-DR, CD38), differentiation (CCR7, CD45RA) and tissue-residency (CD69, CD103, CD49a) on CD4+, CD8+, γδ+ T cells and mucosa-associated invariant T cells using flow cytometry. CD39 expression levels of γδ+ and CD8+ T cells in lamina propria lymphocytes (LPL) were much higher compared to peripheral blood mononuclear cells. Moreover, the frequency of CD39+ CD4+ and CD8+, but not γδ+ LPL positively correlated with T-cell activation. The frequency of CD39+ cells among tissue-resident memory LPL (Trm) was higher compared to non-Trm for all subsets, confirming that CD39 is a marker for the tissue-resident memory phenotype. γδ+ Trm also showed a distinct cytokine profile upon stimulation – the frequency of IFN-γ+ and IL-17A+ cells was significantly lower in γδ+ Trm compared to non-Trm. Interestingly, we observed a decreased frequency of CD39+ γδ+ T cells in IBD patients compared to healthy controls (p = 0.0049). Prospective studies need to elucidate the exact role of this novel CD39+ γδ+ T-cell population with tissue-resident memory phenotype and its possible contribution to the pathogenesis of IBD and other inflammatory disorders.
Jana Libera; Melanie Wittner; Marcus Kantowski; Robin Woost; Johanna M. Eberhard; Jocelyn De Heer; Dominik Reher; Samuel Huber; Friedrich Haag; Julian Schulze Zur Wiesch. Decreased Frequency of Intestinal CD39+ γδ+ T Cells With Tissue-Resident Memory Phenotype in Inflammatory Bowel Disease. Frontiers in Immunology 2020, 11, 1 .
AMA StyleJana Libera, Melanie Wittner, Marcus Kantowski, Robin Woost, Johanna M. Eberhard, Jocelyn De Heer, Dominik Reher, Samuel Huber, Friedrich Haag, Julian Schulze Zur Wiesch. Decreased Frequency of Intestinal CD39+ γδ+ T Cells With Tissue-Resident Memory Phenotype in Inflammatory Bowel Disease. Frontiers in Immunology. 2020; 11 ():1.
Chicago/Turabian StyleJana Libera; Melanie Wittner; Marcus Kantowski; Robin Woost; Johanna M. Eberhard; Jocelyn De Heer; Dominik Reher; Samuel Huber; Friedrich Haag; Julian Schulze Zur Wiesch. 2020. "Decreased Frequency of Intestinal CD39+ γδ+ T Cells With Tissue-Resident Memory Phenotype in Inflammatory Bowel Disease." Frontiers in Immunology 11, no. : 1.
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.
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 StyleThomas 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 StyleThomas 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.
In vitro cell culture experiments and animal models have demonstrated that hepatitis delta virus (HDV) can theoretically propagate being enveloped by human pathogenic viruses other than hepatitis B virus (HBV), namely hepatitis C virus (HCV) and dengue virus. However, the clinical relevance of these findings, and whether HDV replication occurs in real‐world hepatitis B surface antigen (HBsAg) negative HCV patient cohorts remains unknown. To this aim, we analysed 323 HCV‐RNA positive and HBsAg negative sera for the presence of HDV‐RNA and anti‐HDV antibodies (anti‐HDV). All 323 (100%) samples were negative for HDV‐RNA. Interestingly, 8/316 samples tested positive for anti‐HDV. The HBV‐serology of these eight patients showed a positive result for HBV core antibodies (anti‐HBc) indicating a seroconversion of an acute HBV infection in the past. None of the anti‐HBc negative patients were positive for anti‐HDV. Our results indicate a distinctly low probability of replicative HDV infection in HCV mono‐infected patients in Germany. Current German clinical guidelines rightly recommend performing HDV screening only in HBsAg positive patients. However, larger studies on this subject should be performed in regions that are endemic for chronic HBV/HDV as well as HCV infections.
Lisa Sophie Pflüger; Julian Schulze Zur Wiesch; Susanne Polywka; Marc Lütgehetmann. Hepatitis delta virus propagation enabled by hepatitis C virus—Scientifically intriguing, but is it relevant to clinical practice? Journal of Viral Hepatitis 2020, 28, 213 -216.
AMA StyleLisa Sophie Pflüger, Julian Schulze Zur Wiesch, Susanne Polywka, Marc Lütgehetmann. Hepatitis delta virus propagation enabled by hepatitis C virus—Scientifically intriguing, but is it relevant to clinical practice? Journal of Viral Hepatitis. 2020; 28 (1):213-216.
Chicago/Turabian StyleLisa Sophie Pflüger; Julian Schulze Zur Wiesch; Susanne Polywka; Marc Lütgehetmann. 2020. "Hepatitis delta virus propagation enabled by hepatitis C virus—Scientifically intriguing, but is it relevant to clinical practice?" Journal of Viral Hepatitis 28, no. 1: 213-216.
Coronavirus disease 2019 (COVID-19) which is caused by the novel SARS-CoV-2 virus is a severe flu-like illness which is associated with hyperinflammation and immune dysfunction. The virus induces a strong T and B cell response but little is known about the immune pathology of this viral infection. Acute Plasmodium falciparum malaria also causes acute clinical illness and is characterized by hyperinflammation due to the strong production of pro-inflammatory cytokines and a massive activation of T cells. In malaria, T cells express a variety of co-inhibitory receptors which might be a consequence of their activation but also might limit their overwhelming function. Thus, T cells are implicated in protection as well as in pathology. The outcome of malaria is thought to be a consequence of the balance between co-activation and co-inhibition of T cells. Following the hypothesis that T cells in COVID-19 might have a similar, dual function, we comprehensively characterized the differentiation (CCR7, CD45RO) and activation status (HLA-DR, CD38, CD69, CD226), the co-expression of co-inhibitory molecules (PD1, TIM-3, LAG-3, BTLA, TIGIT), as well as the expression pattern of the transcription factors T-bet and eomes of CD8+ and CD4+ T cells of PBMC of n = 20 SARS-CoV-2 patients compared to n = 10 P. falciparum infected patients and n = 13 healthy controls. Overall, acute COVID-19 and malaria infection resulted in a comparably elevated activation and altered differentiation status of the CD8+ and CD4+ T cell populations. T effector cells of COVID-19 and malaria patients showed higher frequencies of the inhibitory receptors T-cell immunoglobulin mucin-3 (TIM-3) and Lymphocyte-activation gene-3 (LAG-3) which was linked to increased activation levels and an upregulation of the transcription factors T-bet and eomes. COVID-19 patients with a more severe disease course showed higher levels of LAG-3 and TIM-3 than patients with a mild disease course. During recovery, a rapid normalization of these inhibitory receptors could be observed. In summary, comparing the expression of different co-inhibitory molecules in CD8+ and CD4+ T cells in COVID-19 vs. malaria, there is a transient increase of the expression of certain inhibitory receptors like LAG-3 and TIM-3 in COVID-19 in the overall context of acute immune activation.
Marissa Herrmann; Sophia Schulte; Nils H. Wildner; Melanie Wittner; Thomas Theo Brehm; Michael Ramharter; Robin Woost; Ansgar W. Lohse; Thomas Jacobs; Julian Schulze Zur Wiesch. Analysis of Co-inhibitory Receptor Expression in COVID-19 Infection Compared to Acute Plasmodium falciparum Malaria: LAG-3 and TIM-3 Correlate With T Cell Activation and Course of Disease. Frontiers in Immunology 2020, 11, 1 .
AMA StyleMarissa Herrmann, Sophia Schulte, Nils H. Wildner, Melanie Wittner, Thomas Theo Brehm, Michael Ramharter, Robin Woost, Ansgar W. Lohse, Thomas Jacobs, Julian Schulze Zur Wiesch. Analysis of Co-inhibitory Receptor Expression in COVID-19 Infection Compared to Acute Plasmodium falciparum Malaria: LAG-3 and TIM-3 Correlate With T Cell Activation and Course of Disease. Frontiers in Immunology. 2020; 11 ():1.
Chicago/Turabian StyleMarissa Herrmann; Sophia Schulte; Nils H. Wildner; Melanie Wittner; Thomas Theo Brehm; Michael Ramharter; Robin Woost; Ansgar W. Lohse; Thomas Jacobs; Julian Schulze Zur Wiesch. 2020. "Analysis of Co-inhibitory Receptor Expression in COVID-19 Infection Compared to Acute Plasmodium falciparum Malaria: LAG-3 and TIM-3 Correlate With T Cell Activation and Course of Disease." Frontiers in Immunology 11, no. : 1.
The ectonucleotidases CD39 and CD73 regulate immune responses by balancing extracellular ATP and adenosine in inflammation and are likely to be involved in the pathophysiology of COVID-19. Here, we analyzed CD39 and CD73 on different lymphocyte populations in a small cohort of COVID-19 patients and in healthy individuals. We describe a significantly lower level of expression of CD73 on cytotoxic lymphocyte populations, including CD8+ T, natural killer T (NKT), and natural killer (NK) cells, during COVID-19. Interestingly, the decrease of CD73 on CD8+ T cells and NKT cells correlated with serum ferritin levels. Furthermore, we observed distinct functional differences between the CD73+ and CD73- subsets of CD8+ T cells and NKT cells with regard to cytokine/toxin secretion. In COVID-19 patients, the majority of the CD73-CD8+ T cells were capable of secreting granzyme B, perforin, tumor necrosis factor (TNF-α) or interferon-gamma (IFN-γ). To conclude, in this first study of CD39 and CD73 expression of lymphocytes in COVID-19, we show that CD8+ T cells and NKT cells lacking CD73 possess a significantly higher cytotoxic effector functionality compared to their CD73+ counterparts. Future studies should investigate differences of cellular CD39 and CD73 expression in patients at different disease stages and their potential as prognostic markers or targets for immunomodulatory therapies.
Parimah Ahmadi; Philip Hartjen; Matin Kohsar; Silke Kummer; Stefan Schmiedel; Jan-Hendrik Bockmann; Anahita Fathi; Samuel Huber; Friedrich Haag; Julian Schulze Zur Wiesch. Defining the CD39/CD73 Axis in SARS-CoV-2 Infection: The CD73- Phenotype Identifies Polyfunctional Cytotoxic Lymphocytes. Cells 2020, 9, 1750 .
AMA StyleParimah Ahmadi, Philip Hartjen, Matin Kohsar, Silke Kummer, Stefan Schmiedel, Jan-Hendrik Bockmann, Anahita Fathi, Samuel Huber, Friedrich Haag, Julian Schulze Zur Wiesch. Defining the CD39/CD73 Axis in SARS-CoV-2 Infection: The CD73- Phenotype Identifies Polyfunctional Cytotoxic Lymphocytes. Cells. 2020; 9 (8):1750.
Chicago/Turabian StyleParimah Ahmadi; Philip Hartjen; Matin Kohsar; Silke Kummer; Stefan Schmiedel; Jan-Hendrik Bockmann; Anahita Fathi; Samuel Huber; Friedrich Haag; Julian Schulze Zur Wiesch. 2020. "Defining the CD39/CD73 Axis in SARS-CoV-2 Infection: The CD73- Phenotype Identifies Polyfunctional Cytotoxic Lymphocytes." Cells 9, no. 8: 1750.
Marcel S. Woo; David Steins; Vivien Häußler; Matin Kohsar; Friedrich Haag; Birte Elias-Hamp; Christoph Heesen; Marc Lütgehetmann; Julian Schulze Zur Wiesch; Manuel A. Friese. Control of SARS-CoV-2 infection in rituximab-treated neuroimmunological patients. Journal of Neurology 2020, 268, 5 -7.
AMA StyleMarcel S. Woo, David Steins, Vivien Häußler, Matin Kohsar, Friedrich Haag, Birte Elias-Hamp, Christoph Heesen, Marc Lütgehetmann, Julian Schulze Zur Wiesch, Manuel A. Friese. Control of SARS-CoV-2 infection in rituximab-treated neuroimmunological patients. Journal of Neurology. 2020; 268 (1):5-7.
Chicago/Turabian StyleMarcel S. Woo; David Steins; Vivien Häußler; Matin Kohsar; Friedrich Haag; Birte Elias-Hamp; Christoph Heesen; Marc Lütgehetmann; Julian Schulze Zur Wiesch; Manuel A. Friese. 2020. "Control of SARS-CoV-2 infection in rituximab-treated neuroimmunological patients." Journal of Neurology 268, no. 1: 5-7.