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Studying the pathophysiology of coronavirus disease 2019 - a protocol for the Berlin prospective COVID-19 patient cohort (Pa- COVID-19)

Florian Kurth, Maria Roennefarth, Charlotte Thibeault, Victor Corman, Holger Mueller-Redetzky, Mirja Mittermaier, Christoph Ruwwe-Gloesenkamp, Alexander Krannich, Sein Schmidt, Lucie Kretzler, Chantip Dang-Heine, Matthias Rose, Michael Hummel, Andreas Hocke, Ralf Huebner, Marcus Mall, Jobst Roehmel, Ulf Landmesser, Burkert Pieske, Samuel Knauss, Matthias Endres, Joachim Spranger, Frank Mockenhaupt, Frank Tacke, Sascha Treskatsch, Stefan Angermair, Britta Siegmund, Claudia Spies, Steffen Weber-Carstens, Kai-Uwe Eckardt, Alexander Uhrig, Thomas Zoller, Christian Drosten, Norbert Suttorp, Martin Witzenrath, Stefan Hippenstiel, Christoph von Kalle, Leif Erik Sander,

Purpose Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide causing a global health emergency. Pa-COVID-19 aims to provide comprehensive data on clinical course, pathophysiology, immunology and outcome of COVID-19, in order to identify prognostic biomarkers, clinical scores, and therapeutic targets for improved clinical management and preventive interventions. Methods ... Read more >>

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Clinical classifiers of COVID-19 infection from novel ultra-high-throughput proteomics

Christoph Messner, Vadim Demichev, Daniel Wendisch, Laura Michalick, Matthew White, Anja Freiwald, Kathrin Textoris-Taube, Spyros Vernardis, Anna-Sophia Egger, Marco Kreidl, Daniela Ludwig, Christiane Kilian, Federica Agostini, Aleksej Zelezniak, Charlotte Thibeault, Moritz Pfeiffer, Stefan Hippenstiel, Andreas Hocke, Christof von Kalle, Archie Campbell, Caroline Hayward, David Porteous, Riccardo Marioni, Claudia Langenberg, Kathryn Lilley, Wolfgang Kuebler, Michael Muelleder, Christian Drosten, Martin Witzenrath, Florian Kurth, Leif Erik Sander, Markus Ralser,

The COVID-19 pandemic is an unprecedented global challenge. Highly variable in its presentation, spread and clinical outcome, novel point-of-care diagnostic classifiers are urgently required. Here, we describe a set of COVID-19 clinical classifiers discovered using a newly designed low-cost high-throughput mass spectrometry-based platform. Introducing a new sample preparation pipeline coupled ... Read more >>

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Cross-talk between the airway epithelium and activated immune cells defines severity in COVID-19

Robert Lorenz Chua, Soeren Lukassen, Saskia Trump, Bianca Hennig, Daniel Wendisch, Fabian Pott, Olivia Debnath, Loreen Thürmann, Florian Kurth, Julia Kazmierski, Bernd Timmermann, Sven Twardziok, Stefan Schneider, Felix Machleidt, Holger Müller-Redetzky, Alexander Krannich, Sein Schmidt, Felix Balzer, Johannes Liebig, Jennifer Loske, Jürgen Eils, Naveed Ishaque, Christof von Kalle, Andreas Hocke, Martin Witzenrath, Christine Goffinet, Christian Drosten, Sven Laudi, Irina Lehmann, Christian Conrad, Leif-Erik Sander, Roland Eils,

The clinical course of COVID-19 is highly variable, however, underlying host factors and determinants of severe disease are still unknown. Based on single-cell transcriptomes of nasopharyngeal and bronchial samples from clinically well-characterized patients presenting with moderate and critical severities, we reveal the different types and states of airway epithelial cells ... Read more >>

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On Top of the Alveolar Epithelium: Surfactant and the Glycocalyx.

Matthias Ochs, Jan Hegermann, Elena Lopez-Rodriguez, Sara Timm, Geraldine Nouailles, Jasmin Matuszak, Szandor Simmons, Martin Witzenrath, Wolfgang M Kuebler,

Gas exchange in the lung takes place via the air-blood barrier in the septal walls of alveoli. The tissue elements that oxygen molecules have to cross are the alveolar epithelium, the interstitium and the capillary endothelium. The epithelium that lines the alveolar surface is covered by a thin and continuous ... Read more >>

Int J Mol Sci (International journal of molecular sciences)
[2020, 21(9):]

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Presence of SARS-CoV-2 reactive T cells in COVID-19 patients and healthy donors

Julian Braun, Lucie Loyal, Marco Frentsch, Daniel Wendisch, Philipp Georg, Florian Kurth, Stefan Hippenstiel, Manuela Dingeldey, Beate Kruse, Florent Fauchere, Emre Baysal, Maike Mangold, Larissa Henze, Roland Lauster, Marcus Mall, Kirsten Beyer, Jobst Roehmel, Juergen Schmitz, Stefan Miltenyi, Marcel Mueller, Martin Witzenrath, Norbert Suttorp, Florian Kern, Ulf Reimer, Holger Wenschuh, Christian Drosten, Victor Corman, Claudia Giesecke-Thiel, Leif-Erik Sander, Andreas Thiel,

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a rapidly unfolding pandemic, overwhelming health care systems worldwide1. Clinical manifestations of Corona-virus-disease 2019 (COVID-19) vary broadly, ranging from asymptomatic infection to acute respiratory failure and death2, yet the underlying physiological conditions and mechanisms for this high variability are still ... Read more >>

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Chronic liver disease negatively affects outcome in hospitalised patients with community-acquired pneumonia.

Carla Bellinghausen, Mathias W Pletz, Jan Rupp, Martin Witzenrath, Christoph Welsch, Stefan Zeuzem, Jonel Trebicka, Gernot G U Rohde, ,

Gut (Gut)
[2020, :]

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Phage capsid nanoparticles with defined ligand arrangement block influenza virus entry.

Daniel Lauster, Simon Klenk, Kai Ludwig, Saba Nojoumi, Sandra Behren, Lutz Adam, Marlena Stadtmüller, Sandra Saenger, Stephanie Zimmler, Katja Hönzke, Ling Yao, Ute Hoffmann, Markus Bardua, Alf Hamann, Martin Witzenrath, Leif E Sander, Thorsten Wolff, Andreas C Hocke, Stefan Hippenstiel, Sacha De Carlo, Jens Neudecker, Klaus Osterrieder, Nediljko Budisa, Roland R Netz, Christoph Böttcher, Susanne Liese, Andreas Herrmann, Christian P R Hackenberger,

Multivalent interactions at biological interfaces occur frequently in nature and mediate recognition and interactions in essential physiological processes such as cell-to-cell adhesion. Multivalency is also a key principle that allows tight binding between pathogens and host cells during the initial stages of infection. One promising approach to prevent infection is ... Read more >>

Nat Nanotechnol (Nature nanotechnology)
[2020, 15(5):373-379]

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Neutralizing Complement C5a Protects Mice with Pneumococcal Pulmonary Sepsis.

Holger Müller-Redetzky, Ute Kellermann, Sandra-Maria Wienhold, Birgitt Gutbier, Jasmin Lienau, Katharina Hellwig, Katrin Reppe, Eleftheria Letsiou, Thomas Tschernig, Markus Scholz, Peter Ahnert, Christian Maasch, Kai Hoehlig, Sven Klussmann, Axel Vater, Theresa C Firsching, Judith Hoppe, Norbert Suttorp, Martin Witzenrath,

BACKGROUND:Community-acquired pneumonia and associated sepsis cause high mortality despite antibiotic treatment. Uncontrolled inflammatory host responses contribute to the unfavorable outcome by driving lung and extrapulmonary organ failure. The complement fragment C5a holds significant proinflammatory functions and is associated with tissue damage in various inflammatory conditions. The authors hypothesized that C5a ... Read more >>

Anesthesiology (Anesthesiology)
[2020, 132(4):795-807]

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[Community-acquired pneumonia in adults].

Agata Mikolajewska, Martin Witzenrath,

Community-acquired pneumonia (CAP) is one of the most common infectious diseases worldwide. To reduce the high morbidity and mortality of CAP, appropriate diagnosis, risk stratification and therapy are necessary. This review summarizes the current recommendations for the management of CAP in Germany. CAP is often a medical emergency. The management ... Read more >>

Dtsch. Med. Wochenschr. (Deutsche medizinische Wochenschrift (1946))
[2020, 145(6):359-370]

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Endoscopic Lung Volume Reduction: Can Endobronchial Valves Be Safely Removed?

Ralf-Harto Hübner, Christoph Ruwwe-Glösenkamp, Jacopo Saccomanno, Pavlina Lenga, Christian Grah, Carmen Pizarro, Martin Witzenrath, Dirk Skowasch,

Respiration (Respiration; international review of thoracic diseases)
[2020, :1-2]

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Update on the "Choosing Wisely" initiative in infectious diseases in Germany.

Rika Draenert, Norma Jung, ,

PURPOSE:The Choosing Wisely® initiative is an international campaign addressing over- and underuse of diagnostic and therapeutic measures in infectious diseases among others. Since 2016, the German Society for Infectious Diseases (DGI) has constantly designed new items in this regard. Here we report the most recent recommendations. METHODS:The recommendations of the ... Read more >>

Infection (Infection)
[2020, 48(3):317-321]

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Markov State Modelling of Disease Courses and Mortality Risks of Patients with Community-Acquired Pneumonia.

Jens Przybilla, Peter Ahnert, Holger Bogatsch, Frank Bloos, Frank M Brunkhorst, SepNet Critical Care Trials Group, Progress Study Group, Michael Bauer, Markus Loeffler, Martin Witzenrath, Norbert Suttorp, Markus Scholz,

Community-acquired pneumonia (CAP) is one of the most frequent infectious diseases worldwide, with high lethality. Risk evaluation is well established at hospital admission, and re-evaluation is advised for patients at higher risk. However, severe disease courses may develop from all levels of severity. We propose a stochastic continuous-time Markov model ... Read more >>

J Clin Med (Journal of clinical medicine)
[2020, 9(2):]

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Maternal asthma is associated with persistent changes in allergic offspring antibody glycosylation.

Elisa B Sodemann, Sabrina Dähling, Robert Klopfleisch, Ekaterina Boiarina, Didier Cataldo, Moumen M Alhasan, Ali Ö Yildirim, Martin Witzenrath, Christoph Tabeling, Melanie L Conrad,

BACKGROUND:Maternal asthma during pregnancy is considered an environmental risk factor for asthma development in children. Immunoglobulin G (IgG) antibodies that are transferred from the mother to the fetus are known to act in a pro- or anti-inflammatory manner depending on their glycosylation status. OBJECTIVE:Using a mouse model, we examined how ... Read more >>

Clin. Exp. Allergy (Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology)
[2020, 50(4):520-531]

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Indwelling pleural catheters for non-malignant pleural effusions: report on a single centre's 10 years of experience.

Nikolaj Frost, Christoph Ruwwe-Glösenkamp, Matthias Raspe, Martin Brünger, Bettina Temmesfeld-Wollbrück, Norbert Suttorp, Martin Witzenrath,

BACKGROUND:Recurrent pleural effusion is a common cause of dyspnoea, cough and chest pain during the course of infectious pleurisy and non-malignant diseases like congestive heart failure (CHF) or liver cirrhosis with hepatic hydrothorax (HH). With regard to the chronic character of the underlying diseases, indwelling pleural catheters (IPC) are increasingly ... Read more >>

BMJ Open Respir Res (BMJ open respiratory research)
[2020, 7(1):]

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Indwelling pleural catheters for malignancy-associated pleural effusion: report on a single centre's ten years of experience.

Nikolaj Frost, Martin Brünger, Christoph Ruwwe-Glösenkamp, Matthias Raspe, Antje Tessmer, Bettina Temmesfeld-Wollbrück, Dirk Schürmann, Norbert Suttorp, Martin Witzenrath,

INTRODUCTION:Recurrent pleural effusion is a common cause of dyspnoea, cough and chest pain during the course of malignant diseases. Chemical pleurodesis had been the only definitive treatment option until two decades ago. Indwelling pleural catheters (IPC) emerged as an alternative, not only assuring immediate symptom relief but also potentially leading ... Read more >>

BMC Pulm Med (BMC pulmonary medicine)
[2019, 19(1):232]

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Macrolide combination therapy for patients hospitalised with community-acquired pneumonia? An individualised approach supported by machine learning.

Rainer König, Xueqi Cao, Marcus Oswald, Christina Forstner, Gernot Rohde, Jan Rupp, Martin Witzenrath, Tobias Welte, Martin Kolditz, Mathias Pletz, ,

BACKGROUND:The role of macrolide/β-lactam combination therapy in community-acquired pneumonia (CAP) of moderate severity is a matter of debate. Macrolides expand the coverage to atypical pathogens and attenuate pulmonary inflammation, but have been associated with cardiovascular toxicity and drug interactions. We developed a decision tree based on aetiological and clinical parameters, ... Read more >>

Eur. Respir. J. (The European respiratory journal)
[2019, 54(6):]

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The Glycemic Gap and 90-Day Mortality in Community-acquired Pneumonia. A Prospective Cohort Study.

Andreas Vestergaard Jensen, Gertrud Baunbæk Egelund, Stine Bang Andersen, Pelle Trier Petersen, Thomas Benfield, Martin Witzenrath, Gernot Rohde, Pernille Ravn, Daniel Faurholt-Jepsen, ,

Rationale: Hyperglycemia is associated with mortality in patients with community-acquired pneumonia (CAP), and hyperglycemia may be a biomarker of severity. However, hyperglycemia has a major disadvantage because the association is diminished in patients with diabetes mellitus (DM). This hampers the use of hyperglycemia as a biomarker. Accounting for habitual glucose ... Read more >>

Ann Am Thorac Soc (Annals of the American Thoracic Society)
[2019, 16(12):1518-1526]

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Pneumococcal conjugate serotype distribution and predominating role of serotype 3 in German adults with community-acquired pneumonia.

Christina Forstner, Martin Kolditz, Miriam Kesselmeier, Santiago Ewig, Gernot Rohde, Grit Barten-Neiner, Jan Rupp, Martin Witzenrath, Tobias Welte, Mathias W Pletz, ,

INTRODUCTION:Implementation of the 7-valent pneumococcal conjugate vaccine (PCV7) in infant vaccination programs has substantially reduced the burden of PCV7 serotypes also in adult community-acquired pneumonia (CAP). Currently, it is unclear, if this extensive herd protection effect can be extrapolated to the additional 6 serotypes included in the 13-valent pneumococcal conjugate ... Read more >>

Vaccine (Vaccine)
[2020, 38(5):1129-1136]

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Rate and Predictors of Bacteremia in Afebrile Community-Acquired Pneumonia.

Christina Forstner, Vladimir Patchev, Gernot Rohde, Jan Rupp, Martin Witzenrath, Tobias Welte, Heinz Burgmann, Mathias W Pletz, ,

BACKGROUND:Although blood cultures (BCs) are the "gold standard" for detecting bacteremia, the utility of BCs in patients with community-acquired pneumonia (CAP) is controversial. This study describes the proportion of patients with CAP and afebrile bacteremia and identifies the clinical characteristics predicting the necessity for BCs in patients who are afebrile. ... Read more >>

Chest (Chest)
[2020, 157(3):529-539]

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Cardiovascular sequelae of pneumonia.

Markus C Brack, Jasmin Lienau, Wolfgang M Kuebler, Martin Witzenrath,

PURPOSE OF REVIEW:In this brief review, we discuss the current epidemiological data and latest results from basic research on the cardiovascular sequelae after lower respiratory tract infection. RECENT FINDINGS:Novel epidemiological evidence substantiates the association between pneumonia and subsequent cardiovascular events (CVEs) in the short- and long-term after viral or bacterial ... Read more >>

Curr Opin Pulm Med (Current opinion in pulmonary medicine)
[2019, 25(3):257-262]

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Role of Ryanodine Type 2 Receptors in Elementary Ca2+ Signaling in Arteries and Vascular Adaptive Responses.

Mario Kaßmann, István András Szijártó, Concha F García-Prieto, Gang Fan, Johanna Schleifenbaum, Yoland-Marie Anistan, Christoph Tabeling, Yu Shi, Ferdinand le Noble, Martin Witzenrath, Yu Huang, Lajos Markó, Mark T Nelson, Maik Gollasch,

Background Hypertension is the major risk factor for cardiovascular disease, the most common cause of death worldwide. Resistance arteries are capable of adapting their diameter independently in response to pressure and flow-associated shear stress. Ryanodine receptors (RyRs) are major Ca2+-release channels in the sarcoplasmic reticulum membrane of myocytes that contribute ... Read more >>

J Am Heart Assoc (Journal of the American Heart Association)
[2019, 8(9):e010090]

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Mediastinal emphysema after long-distance flight with ketoacidosis and underlying diabetes mellitus type 1.

Gracia Lana Ardila Pardo, Wolfgang Michael Kübler, Martin Witzenrath, Jörg-Wilhelm Oestmann,

A 21-year old female with diabetes mellitus type 1 presented to our hospital's emergency department having suffered from shortness of breath, mild chest pain, and vomiting following her arrival after a long-distance flight two days earlier. Symptoms had since subsided and physical examination was normal. Blood analysis revealed increased D-dimers ... Read more >>

Respirol Case Rep (Respirology case reports)
[2019, 7(5):e00423]

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Sequential organ failure assessment score is an excellent operationalization of disease severity of adult patients with hospitalized community acquired pneumonia - results from the prospective observational PROGRESS study.

Peter Ahnert, Petra Creutz, Katrin Horn, Fabian Schwarzenberger, Michael Kiehntopf, Hamid Hossain, Michael Bauer, Frank Martin Brunkhorst, Konrad Reinhart, Uwe Völker, Trinad Chakraborty, Martin Witzenrath, Markus Löffler, Norbert Suttorp, Markus Scholz, ,

BACKGROUND:CAP (Community acquired pneumonia) is frequent, with a high mortality rate and a high burden on health care systems. Development of predictive biomarkers, new therapeutic concepts, and epidemiologic research require a valid, reproducible, and quantitative measure describing CAP severity. METHODS:Using time series data of 1532 patients enrolled in the PROGRESS ... Read more >>

Crit Care (Critical care (London, England))
[2019, 23(1):110]

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Acute Moraxella catarrhalis Airway Infection of Chronically Smoke-Exposed Mice Increases Mechanisms of Emphysema Development: A Pilot Study.

Katja Fischer, Jan-Moritz Doehn, Christian Herr, Carolin Lachner, Annina Heinrich, Olivia Kershaw, Meike Voss, Max H Jacobson, Achim D Gruber, Matthias Clauss, Martin Witzenrath, Robert Bals, Birgitt Gutbier, Hortense Slevogt,

In chronic obstructive pulmonary disease (COPD), acute exacerbations and emphysema development are characteristics for disease pathology. COPD is complicated by infectious exacerbations with acute worsening of respiratory symptoms with Moraxella catarrhalis as one of the most frequent pathogens. Although cigarette smoke (CS) is the primary risk factor, additional molecular mechanisms ... Read more >>

Eur J Microbiol Immunol (Bp) (European journal of microbiology & immunology)
[2018, 8(4):128-134]

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Delay in antibiotic therapy results in fatal disease outcome in murine pneumococcal pneumonia.

Sarah Berger, Cengiz Goekeri, Shishir K Gupta, Julio Vera, Kristina Dietert, Ulrike Behrendt, Jasmin Lienau, Sandra-Maria Wienhold, Achim D Gruber, Norbert Suttorp, Martin Witzenrath, Geraldine Nouailles,

BACKGROUND:Community-acquired pneumonia (CAP) remains a major cause of death worldwide. Mechanisms underlying the detrimental outcome despite adequate antibiotic therapy and comorbidity management are still not fully understood. METHODS:To model timely versus delayed antibiotic therapy in patients, mice with pneumococcal pneumonia received ampicillin twice a day starting early (24 h) or late ... Read more >>

Crit Care (Critical care (London, England))
[2018, 22(1):287]

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