Publikationen im NUM
Hier finden Sie eine Liste der Publikationen, die im Zusammenhang mit dem Netzwerk Universitätsmedizin in der ersten und zweiten Förderphase entstanden sind.
S. Mücke,
S. Kunze,
V. Kopfnagel,
B. Fösel,
I. Bernemann,
P. Christ,
C. Dolch,
N. Klopp,
B. Lorenz-Depiereux,
T. Illig,
G. Anton and
N. Lindemann,
"Dezentralisiertes Biobanking in NAPKON – nach dem Sammeln ist vor der Herausgabe“.",
05
2023.
G. Anton,
T. Bahmer,
S. Ciesek,
C. Dolch,
B. Fösel,
P. Heuschmann,
V. Kopfnagel,
S. Kunze,
B. Lorenz-Depiereux,
S. Mücke,
M. Nauck,
S. Pullamsetti,
M. Ralser,
J. Reese,
C. Schäfer,
M. Schattschneider,
S. Schreiber,
J. Vehreschild,
M. Witzenrath and
T. Illig,
"Systematische molekulare Analysen der NAPKON Kohorten – ein Überblick.",
05
2023.
B. Lorenz-Depiereux,
M. Scherer,
H. Valentin,
S. Berger,
M. Stecher,
A. Hermes,
M. Müller,
B. Balzuweit,
D. Stahl,
C. Schäfer,
S. Hanss,
J. Schaller,
M. Kraus and
E. Heim,
"Poster NAPKON.vention: Ethik-Koordination in NAPKON",
05
2023.
M. Lebedin,
C. V. García,
L. Spatt,
C. Ratswohl,
C. Thibeault,
L. Ostendorf,
T. Alexander,
F. Paul,
L. E. Sander,
F. Kurth and
K. Rosa,
"Discriminating promiscuous from target-specific autoantibodies in COVID-19. Eur J Immunol",
04
2023.
| DOI: | 10.1002/eji.202250210 |
[en]
K. S. Appel,
R. Geisler,
D. Maier,
O. Miljukov,
S. M. Hopff and
J. J. Vehreschild,
"A systematic review of predictor composition, outcomes, risk of
bias, and validation of COVID-19 prognostic scores",
Clin. Infect. Dis.,
Okt.
2023.
Oxford University Press (OUP).
Abstract:
BACKGROUND: Numerous prognostic scores have been published to support risk stratification for patients with Coronavirus disease 2019 (COVID-19). METHODS: We performed a systematic review to identify the scores for confirmed or clinically assumed COVID-19 cases. An in-depth assessment and risk of bias (ROB) analysis (Prediction model Risk Of Bias ASsessment Tool (PROBAST)) was conducted for scores fulfilling predefined criteria ((I) area under the curve (AUC) $\geq$ 0.75; (II) a separate validation cohort present; (III) training data from a multicenter setting ($\geq$ 2 centers); (IV) point-scale scoring system). RESULTS: Out of 1,522 studies extracted from MEDLINE/Web of Science (20/02/2023), we identified 242 scores for COVID-19 outcome prognosis (mortality 109, severity 116, hospitalization 14, long-term sequelae 3). Most scores were developed using retrospective (75.2%) or single-center (57.1%) cohorts. Predictor analysis revealed the primary use of laboratory data and sociodemographic information in mortality and severity scores. Forty-nine scores were included in the in-depth analysis. The results indicated heterogeneous quality and predictor selection, with only five scores featuring low ROB. Among those, based on the number and heterogeneity of validation studies, only the 4C Mortality Score can be recommended for clinical application so far. CONCLUSION: The application and translation of most existing COVID scores appear unreliable. Guided development and predictor selection would have improved the generalizability of the scores and may enhance pandemic preparedness in the future.
| DOI: | 10.1093/cid/ciad618 |
| Pubmed: | 37879096 |
Abstract:
BACKGROUND: Numerous prognostic scores have been published to support risk stratification for patients with Coronavirus disease 2019 (COVID-19). METHODS: We performed a systematic review to identify the scores for confirmed or clinically assumed COVID-19 cases. An in-depth assessment and risk of bias (ROB) analysis (Prediction model Risk Of Bias ASsessment Tool (PROBAST)) was conducted for scores fulfilling predefined criteria ((I) area under the curve (AUC) $\geq$ 0.75; (II) a separate validation cohort present; (III) training data from a multicenter setting ($\geq$ 2 centers); (IV) point-scale scoring system). RESULTS: Out of 1,522 studies extracted from MEDLINE/Web of Science (20/02/2023), we identified 242 scores for COVID-19 outcome prognosis (mortality 109, severity 116, hospitalization 14, long-term sequelae 3). Most scores were developed using retrospective (75.2%) or single-center (57.1%) cohorts. Predictor analysis revealed the primary use of laboratory data and sociodemographic information in mortality and severity scores. Forty-nine scores were included in the in-depth analysis. The results indicated heterogeneous quality and predictor selection, with only five scores featuring low ROB. Among those, based on the number and heterogeneity of validation studies, only the 4C Mortality Score can be recommended for clinical application so far. CONCLUSION: The application and translation of most existing COVID scores appear unreliable. Guided development and predictor selection would have improved the generalizability of the scores and may enhance pandemic preparedness in the future.
M. Krämer,
M. Ingwersen,
U. Teichgräber,
F. Güttler and
R. consortium,
"Added value of chest CT in a machine learning-based prediction model to rule out COVID-19 before inpatient admission: a retrospective university network study",
European Journal of Radiology,
pp. 110827,
2023.
| DOI: | 10.1016/j.ejrad.2023.110827 |
F. Meng,
J. Kottlors,
R. Shahzad,
H. Liu,
P. Fervers,
Y. Jin,
M. Rinneburger,
D. Le,
M. Weisthoff,
W. Liu,
M. Ni,
Y. Sun,
L. An,
X. Huai,
D. Móré,
A. Giannakis,
I. Kaltenborn,
A. Bucher,
D. Maintz,
L. Zhang,
F. Thiele,
M. Li,
M. Perkuhn,
H. Zhang and
T. Persigehl,
"AI support for accurate and fast radiological diagnosis of COVID-19: an international multicenter, multivendor CT study",
Eur Radiol,
vol. 33,
no. 6,
pp. 4280—91,
2023.
[en]
B. Salzberger,
A. Mellmann,
A. Bludau,
S. Ciesek,
V. Corman,
A. Dilthey,
T. Donker,
T. Eckmanns,
R. Egelkamp,
S. G. Gatermann,
H. Grundmann,
G. Häcker,
M. Kaase,
B. Lange,
M. Mielke,
M. W. Pletz,
T. Semmler,
A. Thürmer,
L. H. Wieler,
T. Wolff,
A. F. Widmer and
S. Scheithauer,
"An appeal for strengthening genomic pathogen surveillance to
improve pandemic preparedness and infection prevention: the
German perspective",
Infection,
vol. 51,
no. 4,
pp. 805—811,
Aug.
2023.
Springer Science and Business Media LLC.
Abstract:
The SARS-CoV-2 pandemic has highlighted the importance of viable infection surveillance and the relevant infrastructure. From a German perspective, an integral part of this infrastructure, genomic pathogen sequencing, was at best fragmentary and stretched to its limits due to the lack or inefficient use of equipment, human resources, data management and coordination. The experience in other countries has shown that the rate of sequenced positive samples and linkage of genomic and epidemiological data (person, place, time) represent important factors for a successful application of genomic pathogen surveillance. Planning, establishing and consistently supporting adequate structures for genomic pathogen surveillance will be crucial to identify and combat future pandemics as well as other challenges in infectious diseases such as multi-drug resistant bacteria and healthcare-associated infections. Therefore, the authors propose a multifaceted and coordinated process for the definition of procedural, legal and technical standards for comprehensive genomic pathogen surveillance in Germany, covering the areas of genomic sequencing, data collection and data linkage, as well as target pathogens. A comparative analysis of the structures established in Germany and in other countries is applied. This proposal aims to better tackle epi- and pandemics to come and take action from the "lessons learned" from the SARS-CoV-2 pandemic.
Abstract:
The SARS-CoV-2 pandemic has highlighted the importance of viable infection surveillance and the relevant infrastructure. From a German perspective, an integral part of this infrastructure, genomic pathogen sequencing, was at best fragmentary and stretched to its limits due to the lack or inefficient use of equipment, human resources, data management and coordination. The experience in other countries has shown that the rate of sequenced positive samples and linkage of genomic and epidemiological data (person, place, time) represent important factors for a successful application of genomic pathogen surveillance. Planning, establishing and consistently supporting adequate structures for genomic pathogen surveillance will be crucial to identify and combat future pandemics as well as other challenges in infectious diseases such as multi-drug resistant bacteria and healthcare-associated infections. Therefore, the authors propose a multifaceted and coordinated process for the definition of procedural, legal and technical standards for comprehensive genomic pathogen surveillance in Germany, covering the areas of genomic sequencing, data collection and data linkage, as well as target pathogens. A comparative analysis of the structures established in Germany and in other countries is applied. This proposal aims to better tackle epi- and pandemics to come and take action from the "lessons learned" from the SARS-CoV-2 pandemic.
[en]
F. Steinbeis,
C. Thibeault,
S. Steinbrecher,
Y. Ahlgrimm,
I. A. Haack,
D. August,
B. Balzuweit,
C. Bellinghausen,
S. Berger,
I. Chaplinskaya-Sobol,
O. Cornely,
P. Doeblin,
M. Endres,
C. Fink,
C. Finke,
S. Frank,
S. Hanß,
T. Hartung,
J. C. Hellmuth,
S. Herold,
P. Heuschmann,
J. Heyckendorf,
R. Heyder,
S. Hippenstiel,
W. Hoffmann,
S. U. Kelle,
P. Knape,
P. Koehler,
L. Kretzler,
D. M. Leistner,
J. Lienau,
R. Lorbeer,
B. Lorenz-Depiereux,
C. D. Lüttke,
K. Mai,
U. Merle,
L. A. Meyer-Arndt,
O. Miljukov,
M. Muenchhoff,
M. Müller-Plathe,
J. Neuhann,
H. Neuhauser,
A. Nieters,
C. Otte,
D. Pape,
R. M. Pinto,
C. Pley,
A. Pudszuhn,
P. Reuken,
S. Rieg,
P. Ritter,
G. Rohde,
M. Rönnefarth,
M. Ruzicka,
J. Schaller,
A. Schmidt,
S. Schmidt,
V. Schwachmeyer,
G. Schwanitz,
W. Seeger,
D. Stahl,
N. Stobäus,
H. C. Stubbe,
N. Suttorp,
B. Temmesfeld,
S. Thun,
P. Triller,
F. Trinkmann,
I. Vadasz,
H. Valentin,
M. Vehreschild,
C. Kalle,
M. Lilienfeld-Toal,
J. Weber,
T. Welte,
C. Wildberg,
R. Wizimirski,
S. Zvork,
L. E. Sander,
J. Vehreschild,
T. Zoller,
F. Kurth and
M. Witzenrath,
"Analysis of acute COVID-19 including chronic morbidity:
protocol for the deep phenotyping National Pandemic Cohort
Network in Germany (NAPKON-HAP)",
Infection,
vol. 52,
no. 1,
pp. 93-104,
Jul.
2023.
Abstract:
BACKGROUND: The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) pandemic causes a high burden of acute and long-term morbidity and mortality worldwide despite global efforts in containment, prophylaxis, and therapy. With unprecedented speed, the global scientific community has generated pivotal insights into the pathogen and the host response evoked by the infection. However, deeper characterization of the pathophysiology and pathology remains a high priority to reduce morbidity and mortality of coronavirus disease 2019 (COVID-19). METHODS: NAPKON-HAP is a multi-centered prospective observational study with a long-term follow-up phase of up to 36 months post-SARS-CoV-2 infection. It constitutes a central platform for harmonized data and biospecimen for interdisciplinary characterization of acute SARS-CoV-2 infection and long-term outcomes of diverging disease severities of hospitalized patients. RESULTS: Primary outcome measures include clinical scores and quality of life assessment captured during hospitalization and at outpatient follow-up visits to assess acute and chronic morbidity. Secondary measures include results of biomolecular and immunological investigations and assessment of organ-specific involvement during and post-COVID-19 infection. NAPKON-HAP constitutes a national platform to provide accessibility and usability of the comprehensive data and biospecimen collection to global research. CONCLUSION: NAPKON-HAP establishes a platform with standardized high-resolution data and biospecimen collection of hospitalized COVID-19 patients of different disease severities in Germany. With this study, we will add significant scientific insights and provide high-quality data to aid researchers to investigate COVID-19 pathophysiology, pathology, and chronic morbidity.
| DOI: | 10.1007/s15010-023-02057-0 |
| Pubmed: | 37434025 |
Abstract:
BACKGROUND: The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) pandemic causes a high burden of acute and long-term morbidity and mortality worldwide despite global efforts in containment, prophylaxis, and therapy. With unprecedented speed, the global scientific community has generated pivotal insights into the pathogen and the host response evoked by the infection. However, deeper characterization of the pathophysiology and pathology remains a high priority to reduce morbidity and mortality of coronavirus disease 2019 (COVID-19). METHODS: NAPKON-HAP is a multi-centered prospective observational study with a long-term follow-up phase of up to 36 months post-SARS-CoV-2 infection. It constitutes a central platform for harmonized data and biospecimen for interdisciplinary characterization of acute SARS-CoV-2 infection and long-term outcomes of diverging disease severities of hospitalized patients. RESULTS: Primary outcome measures include clinical scores and quality of life assessment captured during hospitalization and at outpatient follow-up visits to assess acute and chronic morbidity. Secondary measures include results of biomolecular and immunological investigations and assessment of organ-specific involvement during and post-COVID-19 infection. NAPKON-HAP constitutes a national platform to provide accessibility and usability of the comprehensive data and biospecimen collection to global research. CONCLUSION: NAPKON-HAP establishes a platform with standardized high-resolution data and biospecimen collection of hospitalized COVID-19 patients of different disease severities in Germany. With this study, we will add significant scientific insights and provide high-quality data to aid researchers to investigate COVID-19 pathophysiology, pathology, and chronic morbidity.
[en]
D. Hellwig,
N. C. Hellwig,
S. Boehner,
T. Fuchs,
R. Fischer and
D. Schmidt,
"Artificial intelligence and deep learning for advancing PET image reconstruction: State-of-the-art and future directions",
Nuklearmedizin,
vol. 62,
no. 6,
pp. 334—342,
2023.
Georg Thieme Verlag KG,
http://dx.doi.org/10.1055/a-2198-0358.
Abstract:
Positron emission tomography (PET) is vital for diagnosing diseases and monitoring treatments. Conventional image reconstruction (IR) techniques like filtered backprojection and iterative algorithms are powerful but face limitations. PET IR can be seen as an image-to-image translation. Artificial intelligence (AI) and deep learning (DL) using multilayer neural networks enable a new approach to this computer vision task. This review aims to provide mutual understanding for nuclear medicine professionals and AI researchers. We outline fundamentals of PET imaging as well as state-of-the-art in AI-based PET IR with its typical algorithms and DL architectures. Advances improve resolution and contrast recovery, reduce noise, and remove artifacts via inferred attenuation and scatter correction, sinogram inpainting, denoising, and super-resolution refinement. Kernel-priors support list-mode reconstruction, motion correction, and parametric imaging. Hybrid approaches combine AI with conventional IR. Challenges of AI-assisted PET IR include availability of training data, cross-scanner compatibility, and the risk of hallucinated lesions. The need for rigorous evaluations, including quantitative phantom validation and visual comparison of diagnostic accuracy against conventional IR, is highlighted along with regulatory issues. First approved AI-based applications are clinically available, and its impact is foreseeable. Emerging trends, such as the integration of multimodal imaging and the use of data from previous imaging visits, highlight future potentials. Continued collaborative research promises significant improvements in image quality, quantitative accuracy, and diagnostic performance, ultimately leading to the integration of AI-based IR into routine PET imaging protocols.
| DOI: | 10.1055/a-2198-0358 |
Abstract:
Positron emission tomography (PET) is vital for diagnosing diseases and monitoring treatments. Conventional image reconstruction (IR) techniques like filtered backprojection and iterative algorithms are powerful but face limitations. PET IR can be seen as an image-to-image translation. Artificial intelligence (AI) and deep learning (DL) using multilayer neural networks enable a new approach to this computer vision task. This review aims to provide mutual understanding for nuclear medicine professionals and AI researchers. We outline fundamentals of PET imaging as well as state-of-the-art in AI-based PET IR with its typical algorithms and DL architectures. Advances improve resolution and contrast recovery, reduce noise, and remove artifacts via inferred attenuation and scatter correction, sinogram inpainting, denoising, and super-resolution refinement. Kernel-priors support list-mode reconstruction, motion correction, and parametric imaging. Hybrid approaches combine AI with conventional IR. Challenges of AI-assisted PET IR include availability of training data, cross-scanner compatibility, and the risk of hallucinated lesions. The need for rigorous evaluations, including quantitative phantom validation and visual comparison of diagnostic accuracy against conventional IR, is highlighted along with regulatory issues. First approved AI-based applications are clinically available, and its impact is foreseeable. Emerging trends, such as the integration of multimodal imaging and the use of data from previous imaging visits, highlight future potentials. Continued collaborative research promises significant improvements in image quality, quantitative accuracy, and diagnostic performance, ultimately leading to the integration of AI-based IR into routine PET imaging protocols.
[en]
M. Harries,
V. K. Jaeger,
I. Rodiah,
M. J. Hassenstein,
J. Ortmann,
M. Dreier,
I. Holt,
M. Brinkmann,
A. Dulovic,
D. Gornyk,
O. Hovardovska,
C. Kuczewski,
M. A. Kurosinski,
M. Schlotz,
N. Schneiderhan-Marra,
M. Strengert,
G. Krause,
M. Sester,
F. Klein,
A. Petersmann,
A. Karch and
B. Lange,
"Bridging the gap - estimation of 2022/2023 SARS-CoV-2
healthcare burden in Germany based on multidimensional data from
a rapid epidemic panel",
Int. J. Infect. Dis.,
Nov.
2023.
Abstract:
INTRODUCTION: Throughout the SARS-CoV-2 pandemic, Germany like other countries lacked adaptive population-based panels to monitor the spread of epidemic diseases. METHODS: To fill a gap of population-based estimates needed for winter 2022/23 we resampled in the German SARS-CoV-2 cohort study MuSPAD in mid-2022, including characterization of systemic cellular and humoral immune responses by interferon-$\gamma$-release assay (IGRA) and CLIA/IVN assay. We were able to confirm categorization of our study population into four groups with differing protection levels against severe COVID-19 course based on literature synthesis. Using these estimates we assessed potential health care burden for winter 2022/23 in different scenarios with varying assumptions on transmissibility, pathogenicity, new variants, and vaccine booster campaigns in ordinary differential equation models. RESULTS: We included 9921 participants from eight German regions. While 85% of individuals were located in one of the two highest protection categories, hospitalization estimates from scenario modelling were highly dependent on viral variant characteristics ranging from 30-300% compared to the 02/2021 peak. Our results were openly communicated and published to an epidemic panel network and a newly established modelling network. CONCLUSION: We demonstrate feasibility of a rapid epidemic panel to provide complex immune protection levels for inclusion in dynamic disease burden modelling scenarios.
Abstract:
INTRODUCTION: Throughout the SARS-CoV-2 pandemic, Germany like other countries lacked adaptive population-based panels to monitor the spread of epidemic diseases. METHODS: To fill a gap of population-based estimates needed for winter 2022/23 we resampled in the German SARS-CoV-2 cohort study MuSPAD in mid-2022, including characterization of systemic cellular and humoral immune responses by interferon-$\gamma$-release assay (IGRA) and CLIA/IVN assay. We were able to confirm categorization of our study population into four groups with differing protection levels against severe COVID-19 course based on literature synthesis. Using these estimates we assessed potential health care burden for winter 2022/23 in different scenarios with varying assumptions on transmissibility, pathogenicity, new variants, and vaccine booster campaigns in ordinary differential equation models. RESULTS: We included 9921 participants from eight German regions. While 85% of individuals were located in one of the two highest protection categories, hospitalization estimates from scenario modelling were highly dependent on viral variant characteristics ranging from 30-300% compared to the 02/2021 peak. Our results were openly communicated and published to an epidemic panel network and a newly established modelling network. CONCLUSION: We demonstrate feasibility of a rapid epidemic panel to provide complex immune protection levels for inclusion in dynamic disease burden modelling scenarios.
V. Kopfnagel,
I. Bernemann,
G. Anton,
T. Illig,
S. Mücke,
C. Dolch,
N. Klopp,
D. Drobek and
M. Kersting,
"Centralized DNA Isolation in the National Pandemic Cohort Network (NAPKON).",
no. ISBN 978-3-8382-1841-0,
pp. 51-52,
2023.
F. Haag,
M. Pech and
A. Surov,
"Chronic-intermittent diffuse alveolar hemorrhage of unknown origin",
Rofo,
2023.
| DOI: | 10.1055/a-2018-3464 |
D. Gagiannis,
C. Hackenbroch,
W. Bloch,
F. Zech,
F. Kirchhoff,
S. Djudjaj,
S. Stillfried,
R. Bülow,
P. Boor and
K. Steinestel,
"Clinical, Imaging, and Histopathological Features of Pulmonary Sequelae Following Mild COVID-19",
American Journal of Respiratory and Critical Care Medicine,
Jun.
2023.
| DOI: | 10.1164/rccm.202302-0285LE |
| Datei: | https://www.atsjournals.org/doi/abs/10.1164/rccm.202302-0285LE |
S. Arasteh,
P. Isfort,
M. Saehn,
G. Mueller-Franzes,
F. Khader,
J. Kather,
C. Kuhl,
S. Nebelung and
D. Truhn,
"Collaborative training of medical artificial intelligence models with non-uniform labels",
Sci Rep,
vol. 13,
pp. 6046,
2023.
| DOI: | https://doi.org/10.1038/s41598-023-33303-y |
| Pubmed: | 37055456 |
I. Bernemann,
S. Haag,
B. Fösel,
C. Dolch,
N. Klopp,
V. Kopfnagel,
A. Kühn-Steven,
S. Kunze,
S. Mücke,
I. Ruhl,
M. Schieck,
T. Illig and
G. Anton,
"Compliance with study standards in multicentre studies using the example of NAPKON.",
no. ISBN 978-3-8382-1841-0,
pp. 61-62,
2023.
[eng]
K. Bräutigam,
S. Reinhard,
M. Wartenberg,
S. Forster,
K. Greif,
M. Granai,
H. Bösmüller,
K. Klingel and
C. M. Schürch,
"Comprehensive analysis of SARS-CoV-2 receptor proteins in human respiratory tissues identifies alveolar macrophages as potential virus entry site",
Histopathology,
vol. 82,
no. 6,
pp. 846—859,
Mai
2023.
Abstract:
AIMS: COVID-19 has had enormous consequences on global health-care and has resulted in millions of fatalities. The exact mechanism and site of SARS-CoV-2 entry into the body remains insufficiently understood. Recently, novel virus receptors were identified, and alveolar macrophages were suggested as a potential viral entry cell type and vector for intra-alveolar virus transmission. Here, we investigated the protein expression of 10 well-known and novel virus entry molecules along potential entry sites in humans using immunohistochemistry. METHODS AND RESULTS: Samples of different anatomical sites from up to 93 patients were incorporated into tissue microarrays. Protein expression of ACE2, TMPRSS2, furin, CD147, C-type lectin receptors (CD169, CD209, CD299), neuropilin-1, ASGR1 and KREMEN1 were analysed. In lung tissues, at least one of the three receptors ACE2, ASGR1 or KREMEN1 was expressed in the majority of cases. Moreover, all the investigated molecules were found to be expressed in alveolar macrophages, and co-localisation with SARS-CoV-2 N-protein was demonstrated using dual immunohistochemistry in lung tissue from a COVID-19 autopsy. While CD169 and CD209 showed consistent protein expression in sinonasal, conjunctival and bronchiolar tissues, neuropilin-1 and ASGR1 were mostly absent, suggesting a minor relevance of these two molecules at these specific sites. CONCLUSION: Our results extend recent discoveries indicating a role for these molecules in virus entry at different anatomical sites. Moreover, they support the notion of alveolar macrophages being a potential entry cell for SARS-CoV-2.
| DOI: | 10.1111/his.14871 |
Abstract:
AIMS: COVID-19 has had enormous consequences on global health-care and has resulted in millions of fatalities. The exact mechanism and site of SARS-CoV-2 entry into the body remains insufficiently understood. Recently, novel virus receptors were identified, and alveolar macrophages were suggested as a potential viral entry cell type and vector for intra-alveolar virus transmission. Here, we investigated the protein expression of 10 well-known and novel virus entry molecules along potential entry sites in humans using immunohistochemistry. METHODS AND RESULTS: Samples of different anatomical sites from up to 93 patients were incorporated into tissue microarrays. Protein expression of ACE2, TMPRSS2, furin, CD147, C-type lectin receptors (CD169, CD209, CD299), neuropilin-1, ASGR1 and KREMEN1 were analysed. In lung tissues, at least one of the three receptors ACE2, ASGR1 or KREMEN1 was expressed in the majority of cases. Moreover, all the investigated molecules were found to be expressed in alveolar macrophages, and co-localisation with SARS-CoV-2 N-protein was demonstrated using dual immunohistochemistry in lung tissue from a COVID-19 autopsy. While CD169 and CD209 showed consistent protein expression in sinonasal, conjunctival and bronchiolar tissues, neuropilin-1 and ASGR1 were mostly absent, suggesting a minor relevance of these two molecules at these specific sites. CONCLUSION: Our results extend recent discoveries indicating a role for these molecules in virus entry at different anatomical sites. Moreover, they support the notion of alveolar macrophages being a potential entry cell for SARS-CoV-2.
[en]
J. Schädler,
A. T. Azeke,
B. Ondruschka,
S. Steurer,
M. Lütgehetmann,
A. Fitzek and
D. Möbius,
"Concordance between MITS and conventional autopsies for pathological and virological diagnoses",
International Journal of Legal Medicine,
Okt.
2023.
Abstract:
In pandemics or to further study highly contagious infectious diseases, new strategies are needed for the collection of post-mortem tissue samples to identify the pathogen as well as its morphological impact. In this study, an ultrasound-guided minimally invasive tissue sampling (MITS) protocol was developed and validated for post-mortem use. The histological and microbiological qualities of post-mortem specimens were evaluated and compared between MITS and conventional autopsy (CA) in a series of COVID-19 deaths. Thirty-six ultrasound-guided MITS were performed. In five cases more, specimens for histological and virological examination were also obtained and compared during the subsequently performed CA. Summary statistics and qualitative interpretations (positive, negative) were calculated for each organ tissue sample from MITS and CA, and target genes were determined for both human cell count (beta-globin) and virus (SARS-CoV-2 specific E gene). There are no significant differences between MITS and CA with respect to the detectability of viral load in individual organs, which is why MITS can be of utmost importance and an useful alternative, especially during outbreaks of infectious diseases.
| DOI: | 10.1007/s00414-023-03088-w |
| Datei: | https://doi.org/10.1007/s00414-023-03088-w |
Abstract:
In pandemics or to further study highly contagious infectious diseases, new strategies are needed for the collection of post-mortem tissue samples to identify the pathogen as well as its morphological impact. In this study, an ultrasound-guided minimally invasive tissue sampling (MITS) protocol was developed and validated for post-mortem use. The histological and microbiological qualities of post-mortem specimens were evaluated and compared between MITS and conventional autopsy (CA) in a series of COVID-19 deaths. Thirty-six ultrasound-guided MITS were performed. In five cases more, specimens for histological and virological examination were also obtained and compared during the subsequently performed CA. Summary statistics and qualitative interpretations (positive, negative) were calculated for each organ tissue sample from MITS and CA, and target genes were determined for both human cell count (beta-globin) and virus (SARS-CoV-2 specific E gene). There are no significant differences between MITS and CA with respect to the detectability of viral load in individual organs, which is why MITS can be of utmost importance and an useful alternative, especially during outbreaks of infectious diseases.
K. O. Yusuf,
A. Schoneberg,
S. Hanß,
M. Wiesenfeldt,
M. Stecher,
L. Mitrov,
S. M. Hopff,
S. Steinbrecher,
F. Kurth,
T. Bahmer,
S. Schreiber,
D. Pape,
A. Hofmann,
M. Kohls,
S. Störk,
H. C. Stubbe,
J. J. Tebbe,
J. C. Hellmuth,
J. Erber,
L. Krist,
S. Rieg,
L. Pilgram,
J. J. Vehreschild,
J. Reese and
D. Krefting,
"Consistency as a Data Quality Measure for German Corona
Consensus Items Mapped from National Pandemic Cohort Network
Data Collections",
Methods Inf Med,
vol. 62,
no. S 01,
pp. e47—e56,
Jan.
2023.
Georg Thieme Verlag KG.
Abstract:
Background As a national effort to better understand the current pandemic, three cohorts collect sociodemographic and clinical data from coronavirus disease 2019 (COVID-19) patients from different target populations within the German National Pandemic Cohort Network (NAPKON). Furthermore, the German Corona Consensus Dataset (GECCO) was introduced as a harmonized basic information model for COVID-19 patients in clinical routine. To compare the cohort data with other GECCO-based studies, data items are mapped to GECCO. As mapping from one information model to another is complex, an additional consistency evaluation of the mapped items is recommended to detect possible mapping issues or source data inconsistencies.Objectives The goal of this work is to assure high consistency of research data mapped to the GECCO data model. In particular, it aims at identifying contradictions within interdependent GECCO data items of the German national COVID-19 cohorts to allow investigation of possible reasons for identified contradictions. We furthermore aim at enabling other researchers to easily perform data quality evaluation on GECCO-based datasets and adapt to similar data models.Methods All suitable data items from each of the three NAPKON cohorts are mapped to the GECCO items. A consistency assessment tool (dqGecco) is implemented, following the design of an existing quality assessment framework, retaining their-defined consistency taxonomies, including logical and empirical contradictions. Results of the assessment are verified independently on the primary data source.Results Our consistency assessment tool helped in correcting the mapping procedure and reveals remaining contradictory value combinations within COVID-19 symptoms, vital signs, and COVID-19 severity. Consistency rates differ between the different indicators and cohorts ranging from 95.84% up to 100%.Conclusion An efficient and portable tool capable of discovering inconsistencies in the COVID-19 domain has been developed and applied to three different cohorts. As the GECCO dataset is employed in different platforms and studies, the tool can be directly applied there or adapted to similar information models.
| DOI: | 10.1055/a-2006-1086 |
Abstract:
Background As a national effort to better understand the current pandemic, three cohorts collect sociodemographic and clinical data from coronavirus disease 2019 (COVID-19) patients from different target populations within the German National Pandemic Cohort Network (NAPKON). Furthermore, the German Corona Consensus Dataset (GECCO) was introduced as a harmonized basic information model for COVID-19 patients in clinical routine. To compare the cohort data with other GECCO-based studies, data items are mapped to GECCO. As mapping from one information model to another is complex, an additional consistency evaluation of the mapped items is recommended to detect possible mapping issues or source data inconsistencies.Objectives The goal of this work is to assure high consistency of research data mapped to the GECCO data model. In particular, it aims at identifying contradictions within interdependent GECCO data items of the German national COVID-19 cohorts to allow investigation of possible reasons for identified contradictions. We furthermore aim at enabling other researchers to easily perform data quality evaluation on GECCO-based datasets and adapt to similar data models.Methods All suitable data items from each of the three NAPKON cohorts are mapped to the GECCO items. A consistency assessment tool (dqGecco) is implemented, following the design of an existing quality assessment framework, retaining their-defined consistency taxonomies, including logical and empirical contradictions. Results of the assessment are verified independently on the primary data source.Results Our consistency assessment tool helped in correcting the mapping procedure and reveals remaining contradictory value combinations within COVID-19 symptoms, vital signs, and COVID-19 severity. Consistency rates differ between the different indicators and cohorts ranging from 95.84% up to 100%.Conclusion An efficient and portable tool capable of discovering inconsistencies in the COVID-19 domain has been developed and applied to three different cohorts. As the GECCO dataset is employed in different platforms and studies, the tool can be directly applied there or adapted to similar information models.
K. O. Yusuf,
O. Miljukov,
A. Schoneberg,
S. Hanß,
M. Wiesenfeldt,
M. Stecher,
L. Mitrov,
S. Hopff,
S. Steinbrecher,
F. Kurth,
T. Bahmer,
S. Schreiber,
D. Pape,
A. Hofmann,
M. Kohls,
S. Störk,
H. C. Stubbe,
J. J. Tebbe,
J. Hellmuth,
J. Erber,
L. Krist,
S. Rieg,
L. Pilgram,
J. J. Vehreschild,
J. Reese and
D. Krefting,
"Consistency as a Data Quality Measure for German Corona Consensus Items Mapped from National Pandemic Cohort Network Data Collections.",
01
2023.
| DOI: | 10.1055/a-2006-1086 |
H. Meyer,
H. Kardas,
C. Bär,
D. Schramm,
A. Wienke,
J. Borggrefe and
A. Surov,
"CT-defined pectoralis muscle mass and muscle density are associated with mortality in acute pulmonary embolism. A multicenter analysis",
Clinical Nutrition,
vol. 42,
no. 6,
pp. 1036—1040,
2023.
[en]
S. Stanelle-Bertram,
S. Beck,
N. K. Mounogou,
B. Schaumburg,
F. Stoll,
A. Al Jawazneh,
Z. Schmal,
T. Bai,
M. Zickler,
G. Beythien,
K. Becker,
M. Roi,
F. Heinrich,
C. Schulz,
M. Sauter,
S. Krasemann,
P. Lange,
A. Heinemann,
D. Riel,
L. Leijten,
L. Bauer,
T. P. P. Bosch,
B. Lopuhaä,
T. Busche,
D. Wibberg,
D. Schaudien,
T. Goldmann,
A. Lüttjohann,
J. Ruschinski,
H. Jania,
Z. Müller,
V. Reis,
V. Krupp-Buzimkic,
M. Wolff,
C. Fallerini,
M. Baldassarri,
S. Furini,
K. Norwood,
C. Käufer,
N. Schützenmeister,
M. Köckritz-Blickwede,
M. Schroeder,
D. Jarczak,
A. Nierhaus,
T. Welte,
S. Kluge,
A. C. McHardy,
F. Sommer,
J. Kalinowski,
S. Krauss-Etschmann,
F. Richter,
J. Thüsen,
W. Baumgärtner,
K. Klingel,
B. Ondruschka,
A. Renieri and
G. Gabriel,
"CYP19A1 mediates severe SARS-CoV-2 disease outcome in males",
Cell Reports Medicine,
pp. 101152,
Aug.
2023.
Abstract:
Male sex represents one of the major risk factors for severe COVID-19 outcome. However, underlying mechanisms that mediate sex-dependent disease outcome are as yet unknown. Here, we identify the CYP19A1 gene encoding for the testosterone-to-estradiol metabolizing enzyme CYP19A1 (also known as aromatase) as a host factor that contributes to worsened disease outcome in SARS-CoV-2-infected males. We analyzed exome sequencing data obtained from a human COVID-19 cohort (n = 2,866) using a machine-learning approach and identify a CYP19A1-activity-increasing mutation to be associated with the development of severe disease in men but not women. We further analyzed human autopsy-derived lungs (n = 86) and detect increased pulmonary CYP19A1 expression at the time point of death in men compared with women. In the golden hamster model, we show that SARS-CoV-2 infection causes increased CYP19A1 expression in the lung that is associated with dysregulated plasma sex hormone levels and reduced long-term pulmonary function in males but not females. Treatment of SARS-CoV-2-infected hamsters with a clinically approved CYP19A1 inhibitor (letrozole) improves impaired lung function and supports recovery of imbalanced sex hormones specifically in males. Our study identifies CYP19A1 as a contributor to sex-specific SARS-CoV-2 disease outcome in males. Furthermore, inhibition of CYP19A1 by the clinically approved drug letrozole may furnish a new therapeutic strategy for individualized patient management and treatment.
| DOI: | 10.1016/j.xcrm.2023.101152 |
| Datei: | https://www.sciencedirect.com/science/article/pii/S2666379123003051 |
Abstract:
Male sex represents one of the major risk factors for severe COVID-19 outcome. However, underlying mechanisms that mediate sex-dependent disease outcome are as yet unknown. Here, we identify the CYP19A1 gene encoding for the testosterone-to-estradiol metabolizing enzyme CYP19A1 (also known as aromatase) as a host factor that contributes to worsened disease outcome in SARS-CoV-2-infected males. We analyzed exome sequencing data obtained from a human COVID-19 cohort (n = 2,866) using a machine-learning approach and identify a CYP19A1-activity-increasing mutation to be associated with the development of severe disease in men but not women. We further analyzed human autopsy-derived lungs (n = 86) and detect increased pulmonary CYP19A1 expression at the time point of death in men compared with women. In the golden hamster model, we show that SARS-CoV-2 infection causes increased CYP19A1 expression in the lung that is associated with dysregulated plasma sex hormone levels and reduced long-term pulmonary function in males but not females. Treatment of SARS-CoV-2-infected hamsters with a clinically approved CYP19A1 inhibitor (letrozole) improves impaired lung function and supports recovery of imbalanced sex hormones specifically in males. Our study identifies CYP19A1 as a contributor to sex-specific SARS-CoV-2 disease outcome in males. Furthermore, inhibition of CYP19A1 by the clinically approved drug letrozole may furnish a new therapeutic strategy for individualized patient management and treatment.
S. Mücke,
S. Kunze,
V. Kopfnagel,
B. Fösel,
I. Bernemann,
C. Dolch,
N. Klopp,
D. Lindemann,
B. Lorenz-Depiereux,
T. Illig,
G. Anton and
P. Christ,
"Decentralized biobanking in NAPKON - 500 sample requests later.",
no. ISBN 978-3-8382-1841-0,
pp. 53-54,
2023.
C. Nürnberger,
K. S. Appel,
M. C. Polidori,
N. Hettich,
T. Bahmer,
C. Förster,
C. Lemhöfer and
On Behalf Of The Napkon Study Group,
"Der Post-COVID-Score ist zur Identifizierung von Betroffenen in der SÜP anwendbar. Die Einbeziehung von Assessmentinstrumenten kann zu einer detaillierteren Darstellung beitragen",
Poster NAPKON Vention 2023, Frankfurt,
2023.
M. Lebedin,
C. V. García,
L. Spatt,
C. Ratswohl,
C. Thibeault,
L. Ostendorf,
T. Alexander,
F. Paul,
L. E. Sander,
F. Kurth and
K. Rosa,
"Discriminating promiscuous from target-specific autoantibodies in COVID-19",
European Journal of Immunology,
vol. 53,
no. 5,
pp. 2250210,
2023.
Abstract:
Abstract Diverse autoantibodies were suggested to contribute to severe outcomes of COVID-19, but their functional implications are largely unclear. ACE2, the SARS-CoV-2 receptor and a key regulator of blood pressure, was described to be one of many targets of autoantibodies in COVID-19. ACE2 in its soluble form (sACE2) is highly elevated in the blood of critically ill patients, raising the question of whether sACE2:spike complexes induce ACE2 reactivity. Screening 247 COVID-19 patients, we observed elevated sACE2 and anti-ACE2 IgG that were poorly correlated. Interestingly, levels of IgGs recognizing ACE2, IFNα2, and CD26 strongly correlated in severe COVID-19, with 15% of sera showing polyreactivity versus 4.1% exhibiting target-directed autoimmunity. Promiscuous autoantibodies failed to impair the activity of ACE2 and IFNα2, while only specific anti-IFNα2 IgG compromised cytokine function. Our study suggests that the detection of autoantibodies in COVID-19 is often attributed to a promiscuous reactivity, potentially misinterpreted as target-specific autoimmunity with functional impact.
| DOI: | 10.1002/eji.202250210 |
| Pubmed: | 36856018 |
| Datei: | https://onlinelibrary.wiley.com/doi/abs/10.1002/eji.202250210 |
Abstract:
Abstract Diverse autoantibodies were suggested to contribute to severe outcomes of COVID-19, but their functional implications are largely unclear. ACE2, the SARS-CoV-2 receptor and a key regulator of blood pressure, was described to be one of many targets of autoantibodies in COVID-19. ACE2 in its soluble form (sACE2) is highly elevated in the blood of critically ill patients, raising the question of whether sACE2:spike complexes induce ACE2 reactivity. Screening 247 COVID-19 patients, we observed elevated sACE2 and anti-ACE2 IgG that were poorly correlated. Interestingly, levels of IgGs recognizing ACE2, IFNα2, and CD26 strongly correlated in severe COVID-19, with 15% of sera showing polyreactivity versus 4.1% exhibiting target-directed autoimmunity. Promiscuous autoantibodies failed to impair the activity of ACE2 and IFNα2, while only specific anti-IFNα2 IgG compromised cytokine function. Our study suggests that the detection of autoantibodies in COVID-19 is often attributed to a promiscuous reactivity, potentially misinterpreted as target-specific autoimmunity with functional impact.
[en]
Z. I. Kolabas,
L. B. Kuemmerle,
R. Perneczky,
B. Förstera,
S. Ulukaya,
M. Ali,
S. Kapoor,
L. M. Bartos,
M. Büttner,
O. S. Caliskan,
Z. Rong,
H. Mai,
L. Höher,
D. Jeridi,
M. Molbay,
I. Khalin,
I. K. Deligiannis,
M. Negwer,
K. Roberts,
A. Simats,
O. Carofiglio,
M. I. Todorov,
I. Horvath,
F. Ozturk,
S. Hummel,
G. Biechele,
A. Zatcepin,
M. Unterrainer,
J. Gnörich,
J. Roodselaar,
J. Shrouder,
P. Khosravani,
B. Tast,
L. Richter,
L. Díaz-Marugán,
D. Kaltenecker,
L. Lux,
Y. Chen,
S. Zhao,
B. Rauchmann,
M. Sterr,
I. Kunze,
K. Stanic,
V. W. Y. Kan,
S. Besson-Girard,
S. Katzdobler,
C. Palleis,
J. Schädler,
J. C. Paetzold,
S. Liebscher,
A. E. Hauser,
O. Gokce,
H. Lickert,
H. Steinke,
C. Benakis,
C. Braun,
C. P. Martinez-Jimenez,
K. Buerger,
N. L. Albert,
G. Höglinger,
J. Levin,
C. Haass,
A. Kopczak,
M. Dichgans,
J. Havla,
T. Kümpfel,
M. Kerschensteiner,
M. Schifferer,
M. Simons,
A. Liesz,
N. Krahmer,
O. A. Bayraktar,
N. Franzmeier,
N. Plesnila,
S. Erener,
V. G. Puelles,
C. Delbridge,
H. S. Bhatia,
F. Hellal,
M. Elsner,
I. Bechmann,
B. Ondruschka,
M. Brendel,
F. J. Theis and
A. Erturk,
"Distinct molecular profiles of skull bone marrow in health and neurological disorders",
Cell,
pp. S0092867423007420,
Aug.
2023.
| DOI: | 10.1016/j.cell.2023.07.009 |
| Datei: | https://linkinghub.elsevier.com/retrieve/pii/S0092867423007420 |
[en]
R. Mothes,
A. Pascual-Reguant,
R. Koehler,
J. Liebeskind,
A. Liebheit,
S. Bauherr,
L. Philipsen,
C. Dittmayer,
M. Laue,
R. Von Manitius,
S. Elezkurtaj,
P. Durek,
F. Heinrich,
G. A. Heinz,
G. M. Guerra,
B. Obermayer,
J. Meinhardt,
J. Ihlow,
J. Radke,
F. L. Heppner,
P. Enghard,
H. Stockmann,
T. Aschman,
J. Schneider,
V. M. Corman,
L. E. Sander,
M. Mashreghi,
T. Conrad,
A. C. Hocke,
R. A. Niesner,
H. Radbruch and
A. E. Hauser,
"Distinct tissue niches direct lung immunopathology via CCL18 and CCL21 in severe COVID-19",
Nature Communications,
vol. 14,
no. 1,
pp. 791,
Feb.
2023.
Abstract:
Abstract Prolonged lung pathology has been associated with COVID-19, yet the cellular and molecular mechanisms behind this chronic inflammatory disease are poorly understood. In this study, we combine advanced imaging and spatial transcriptomics to shed light on the local immune response in severe COVID-19. We show that activated adventitial niches are crucial microenvironments contributing to the orchestration of prolonged lung immunopathology. Up-regulation of the chemokines CCL21 and CCL18 associates to endothelial-to-mesenchymal transition and tissue fibrosis within these niches. CCL21 over-expression additionally links to the local accumulation of T cells expressing the cognate receptor CCR7. These T cells are imprinted with an exhausted phenotype and form lymphoid aggregates that can organize in ectopic lymphoid structures. Our work proposes immune-stromal interaction mechanisms promoting a self-sustained and non-resolving local immune response that extends beyond active viral infection and perpetuates tissue remodeling.
| DOI: | 10.1038/s41467-023-36333-2 |
| Datei: | https://www.nature.com/articles/s41467-023-36333-2 |
Abstract:
Abstract Prolonged lung pathology has been associated with COVID-19, yet the cellular and molecular mechanisms behind this chronic inflammatory disease are poorly understood. In this study, we combine advanced imaging and spatial transcriptomics to shed light on the local immune response in severe COVID-19. We show that activated adventitial niches are crucial microenvironments contributing to the orchestration of prolonged lung immunopathology. Up-regulation of the chemokines CCL21 and CCL18 associates to endothelial-to-mesenchymal transition and tissue fibrosis within these niches. CCL21 over-expression additionally links to the local accumulation of T cells expressing the cognate receptor CCR7. These T cells are imprinted with an exhausted phenotype and form lymphoid aggregates that can organize in ectopic lymphoid structures. Our work proposes immune-stromal interaction mechanisms promoting a self-sustained and non-resolving local immune response that extends beyond active viral infection and perpetuates tissue remodeling.
[en]
T. Fuchs,
L. Kaiser,
D. Müller,
L. Papp,
R. Fischer and
J. Tran-Gia,
"Enhancing interoperability and harmonisation of nuclear medicine image data and associated clinical data",
Nuklearmedizin,
vol. 62,
no. 6,
pp. 389-398,
2023.
Georg Thieme Verlag KG,
http://dx.doi.org/10.1055/a-2187-5701.
Abstract:
Nuclear imaging techniques such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) in combination with computed tomography (CT) are established imaging modalities in clinical practice, particularly for oncological problems. Due to a multitude of manufacturers, different measurement protocols, local demographic or clinical workflow variations as well as various available reconstruction and analysis software, very heterogeneous datasets are generated. This review article examines the current state of interoperability and harmonisation of image data and related clinical data in the field of nuclear medicine. Various approaches and standards to improve data compatibility and integration are discussed. These include, for example, structured clinical history, standardisation of image acquisition and reconstruction as well as standardised preparation of image data for evaluation. Approaches to improve data acquisition, storage and analysis will be presented. Furthermore, approaches are presented to prepare the datasets in such a way that they become usable for projects applying artificial intelligence (AI) (machine learning, deep learning, etc.). This review article concludes with an outlook on future developments and trends related to AI in nuclear medicine, including a brief research of commercial solutions.
| DOI: | 10.1055/a-2187-5701 |
Abstract:
Nuclear imaging techniques such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) in combination with computed tomography (CT) are established imaging modalities in clinical practice, particularly for oncological problems. Due to a multitude of manufacturers, different measurement protocols, local demographic or clinical workflow variations as well as various available reconstruction and analysis software, very heterogeneous datasets are generated. This review article examines the current state of interoperability and harmonisation of image data and related clinical data in the field of nuclear medicine. Various approaches and standards to improve data compatibility and integration are discussed. These include, for example, structured clinical history, standardisation of image acquisition and reconstruction as well as standardised preparation of image data for evaluation. Approaches to improve data acquisition, storage and analysis will be presented. Furthermore, approaches are presented to prepare the datasets in such a way that they become usable for projects applying artificial intelligence (AI) (machine learning, deep learning, etc.). This review article concludes with an outlook on future developments and trends related to AI in nuclear medicine, including a brief research of commercial solutions.
K. Tilch and
S. M. Hopff,
"Entscheidungsverhalten zur Einwilligung in Studienmodule bei Patient:innen des Nationalen Pandemie Kohorten Netzes.",
Poster KIT Kongress 2023, Leipzig,
2023.
[en]
B. Lange,
V. K. Jaeger,
M. Harries,
V. R"ucker,
H. Streeck,
S. Blaschke,
A. Petersmann,
N. Toepfner,
M. Nauck,
M. J. Hassenstein,
M. Dreier,
I. Holt,
A. Budde,
A. Bartz,
J. Ortmann,
M. Kurosinski,
R. Berner,
M. Borsche,
G. Brandhorst,
M. Brinkmann,
K. Budde,
M. Deckena,
G. Engels,
M. Fenzlaff,
C. Härtel,
O. Hovardovska,
A. Katalinic,
K. Kehl,
M. Kohls,
S. Krüger,
W. Lieb,
K. M. Meyer-Schlinkmann,
T. Pischon,
D. Rosenkranz,
N. R"ubsamen,
J. Rupp,
C. Schäfer,
M. Schattschneider,
A. Schlegtendal,
S. Schlinkert,
L. Schmidbauer,
K. Schulze-Wundling,
S. Störk,
C. Tiemann,
H. V"olzke,
T. Winter,
C. Klein,
J. Liese,
F. Brinkmann,
P. F. Ottensmeyer,
J. Reese,
P. Heuschmann and
A. Karch,
"Estimates of protection levels against SARS-CoV-2 infection and
severe COVID-19 in Germany before the 2022/2023 winter season:
the IMMUNEBRIDGE project",
Infection,
Aug.
2023.
Abstract:
PURPOSE: Despite the need to generate valid and reliable estimates of protection levels against SARS-CoV-2 infection and severe course of COVID-19 for the German population in summer 2022, there was a lack of systematically collected population-based data allowing for the assessment of the protection level in real time. METHODS: In the IMMUNEBRIDGE project, we harmonised data and biosamples for nine population-/hospital-based studies (total number of participants n = 33,637) to provide estimates for protection levels against SARS-CoV-2 infection and severe COVID-19 between June and November 2022. Based on evidence synthesis, we formed a combined endpoint of protection levels based on the number of self-reported infections/vaccinations in combination with nucleocapsid/spike antibody responses ("confirmed exposures"). Four confirmed exposures represented the highest protection level, and no exposure represented the lowest. RESULTS: Most participants were seropositive against the spike antigen; 37% of the participants $\geq$ 79 years had less than four confirmed exposures (highest level of protection) and 5% less than three. In the subgroup of participants with comorbidities, 46-56% had less than four confirmed exposures. We found major heterogeneity across federal states, with 4-28% of participants having less than three confirmed exposures. CONCLUSION: Using serological analyses, literature synthesis and infection dynamics during the survey period, we observed moderate to high levels of protection against severe COVID-19, whereas the protection against SARS-CoV-2 infection was low across all age groups. We found relevant protection gaps in the oldest age group and amongst individuals with comorbidities, indicating a need for additional protective measures in these groups.
| DOI: | https://doi.org/10.1007/s15010-023-02071-2 |
Abstract:
PURPOSE: Despite the need to generate valid and reliable estimates of protection levels against SARS-CoV-2 infection and severe course of COVID-19 for the German population in summer 2022, there was a lack of systematically collected population-based data allowing for the assessment of the protection level in real time. METHODS: In the IMMUNEBRIDGE project, we harmonised data and biosamples for nine population-/hospital-based studies (total number of participants n = 33,637) to provide estimates for protection levels against SARS-CoV-2 infection and severe COVID-19 between June and November 2022. Based on evidence synthesis, we formed a combined endpoint of protection levels based on the number of self-reported infections/vaccinations in combination with nucleocapsid/spike antibody responses ("confirmed exposures"). Four confirmed exposures represented the highest protection level, and no exposure represented the lowest. RESULTS: Most participants were seropositive against the spike antigen; 37% of the participants $\geq$ 79 years had less than four confirmed exposures (highest level of protection) and 5% less than three. In the subgroup of participants with comorbidities, 46-56% had less than four confirmed exposures. We found major heterogeneity across federal states, with 4-28% of participants having less than three confirmed exposures. CONCLUSION: Using serological analyses, literature synthesis and infection dynamics during the survey period, we observed moderate to high levels of protection against severe COVID-19, whereas the protection against SARS-CoV-2 infection was low across all age groups. We found relevant protection gaps in the oldest age group and amongst individuals with comorbidities, indicating a need for additional protective measures in these groups.
S. Scheithauer,
A. Dilthey,
A. Bludau,
S. Ciesek,
V. Corman,
T. Donker,
T. Eckmanns,
R. Egelkamp,
H. Grundmann,
G. Häcker,
M. Kaase,
B. Lange,
A. Mellmann,
M. Mielke,
M. Pletz,
B. Salzberger,
A. Thürmer,
A. Widmer,
L. H. Wieler,
T. Wolff,
S. Gatermann and
T. Semmler,
"Etablierung der Genomischen Erreger-Surveillance zur Stärkung des Pandemie- und Infektionsschutzes in Deutschland",
Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz,
vol. 66,
no. 4,
pp. 443—449,
2023.
Abstract:
The SARS-CoV\hbox-2 pandemic has shown a~deficit of essential epidemiological infrastructure, especially with regard to genomic pathogen surveillance in Germany. In order to prepare for future pandemics, the authors consider it urgently necessary to remedy this existing deficit by establishing an efficient infrastructure for genomic pathogen surveillance. Such a network can build on structures, processes, and interactions that have already been initiated regionally and further optimize them. It will be able to respond to current and future challenges with a~high degree of adaptability.The aim of this paper is to address the urgency and to outline proposed measures for establishing an efficient, adaptable, and responsive genomic pathogen surveillance network, taking into account external framework conditions and internal standards. The proposed measures are based on global and country-specific best practices and strategy papers. Specific next steps to achieve an integrated genomic pathogen surveillance include linking epidemiological data with pathogen genomic data; sharing and coordinating existing resources; making surveillance data available to relevant decision-makers, the public health service, and the scientific community; and engaging all stakeholders. The establishment of a~genomic pathogen surveillance network is essential for the continuous, stable, active surveillance of the infection situation in Germany, both during pandemic phases and beyond. Die SARS-CoV-2-Pandemie hat ein Defizit an essentieller infektionsepidemiologischer Infrastruktur, insbesondere in Bezug auf die Genomische Erreger-Surveillance (GES) in Deutschland, gezeigt. Zur Vorbereitung auf zukünftige pandemische Notlagen sehen es die Autor*innen als dringend erforderlich an, dieses bestehende Defizit durch den Aufbau einer leistungsfähigen Infrastruktur für GES zu beheben. Ein derartiges Netzwerk kann auf bereits regional initiierten Strukturen, Prozessen und Interaktionen aufbauen und diese weiter optimieren. Es kann zukünftig mit einer hohen Anpassungsfähigkeit auf aktuelle und kommende Herausforderungen reagieren.Ziele der vorliegenden Arbeit sind die Verdeutlichung der Dringlichkeit und Skizzierung von Vorschlägen zur Etablierung eines effizienten, anpassungsfähigen und reaktionsbereiten GES-Netzwerkes unter Berücksichtigung von externen Rahmenbedingungen und internen Standards. Die erarbeiteten Vorschläge basieren auf der Grundlage globaler und länderspezifischer Best Practices und Strategiepapiere. Zu den konkreten nächsten Schritten zur Realisierung einer integrierten GES zählen die Ermöglichung der Verknüpfung epidemiologischer Daten mit Genomdaten der Erreger, die gemeinsame und koordinierte Nutzung von vorhandenen Ressourcen, die Nutzbarmachung der so gewonnenen Surveillance-Daten für relevante Entscheidungstragende, den Öffentlichen Gesundheitsdienst und die wissenschaftliche Gemeinschaft sowie die Einbindung aller Stakeholder. Der Aufbau eines GES-Netzwerkes ist essentiell für die kontinuierliche, stabile, aktive Überwachung des Infektionsgeschehens in Deutschland sowohl während pandemischer Phasen als auch außerhalb dieser.
| DOI: | 10.1007/s00103-023-03680-w |
Abstract:
The SARS-CoV\hbox-2 pandemic has shown a~deficit of essential epidemiological infrastructure, especially with regard to genomic pathogen surveillance in Germany. In order to prepare for future pandemics, the authors consider it urgently necessary to remedy this existing deficit by establishing an efficient infrastructure for genomic pathogen surveillance. Such a network can build on structures, processes, and interactions that have already been initiated regionally and further optimize them. It will be able to respond to current and future challenges with a~high degree of adaptability.The aim of this paper is to address the urgency and to outline proposed measures for establishing an efficient, adaptable, and responsive genomic pathogen surveillance network, taking into account external framework conditions and internal standards. The proposed measures are based on global and country-specific best practices and strategy papers. Specific next steps to achieve an integrated genomic pathogen surveillance include linking epidemiological data with pathogen genomic data; sharing and coordinating existing resources; making surveillance data available to relevant decision-makers, the public health service, and the scientific community; and engaging all stakeholders. The establishment of a~genomic pathogen surveillance network is essential for the continuous, stable, active surveillance of the infection situation in Germany, both during pandemic phases and beyond. Die SARS-CoV-2-Pandemie hat ein Defizit an essentieller infektionsepidemiologischer Infrastruktur, insbesondere in Bezug auf die Genomische Erreger-Surveillance (GES) in Deutschland, gezeigt. Zur Vorbereitung auf zukünftige pandemische Notlagen sehen es die Autor*innen als dringend erforderlich an, dieses bestehende Defizit durch den Aufbau einer leistungsfähigen Infrastruktur für GES zu beheben. Ein derartiges Netzwerk kann auf bereits regional initiierten Strukturen, Prozessen und Interaktionen aufbauen und diese weiter optimieren. Es kann zukünftig mit einer hohen Anpassungsfähigkeit auf aktuelle und kommende Herausforderungen reagieren.Ziele der vorliegenden Arbeit sind die Verdeutlichung der Dringlichkeit und Skizzierung von Vorschlägen zur Etablierung eines effizienten, anpassungsfähigen und reaktionsbereiten GES-Netzwerkes unter Berücksichtigung von externen Rahmenbedingungen und internen Standards. Die erarbeiteten Vorschläge basieren auf der Grundlage globaler und länderspezifischer Best Practices und Strategiepapiere. Zu den konkreten nächsten Schritten zur Realisierung einer integrierten GES zählen die Ermöglichung der Verknüpfung epidemiologischer Daten mit Genomdaten der Erreger, die gemeinsame und koordinierte Nutzung von vorhandenen Ressourcen, die Nutzbarmachung der so gewonnenen Surveillance-Daten für relevante Entscheidungstragende, den Öffentlichen Gesundheitsdienst und die wissenschaftliche Gemeinschaft sowie die Einbindung aller Stakeholder. Der Aufbau eines GES-Netzwerkes ist essentiell für die kontinuierliche, stabile, aktive Überwachung des Infektionsgeschehens in Deutschland sowohl während pandemischer Phasen als auch außerhalb dieser.
[en]
K. Tilch,
S. M. Hopff,
K. S. Appel,
M. Kraus,
B. Lorenz-Depiereux,
L. Pilgram,
G. Anton,
S. Berger,
R. Geisler,
K. Haas,
T. Illig,
D. Krefting,
R. Lorbeer,
L. Mitrov,
M. Muenchhoff,
M. Nauck,
C. Pley,
J. Reese,
S. Rieg,
M. Scherer,
M. Stecher,
C. Stellbrink,
H. Valentin,
C. Winter,
M. Witzenrath and
J. J. Vehreschild,
"Ethical and coordinative challenges in setting up a national
cohort study during the COVID-19 pandemic in Germany",
BMC Med. Ethics,
vol. 24,
no. 1,
pp. 84,
Okt.
2023.
Abstract:
With the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), global researchers were confronted with major challenges. The German National Pandemic Cohort Network (NAPKON) was launched in fall 2020 to effectively leverage resources and bundle research activities in the fight against the coronavirus disease 2019 (COVID-19) pandemic. We analyzed the setup phase of NAPKON as an example for multicenter studies in Germany, highlighting challenges and optimization potential in connecting 59 university and nonuniversity study sites. We examined the ethics application process of 121 ethics submissions considering durations, annotations, and outcomes. Study site activation and recruitment processes were investigated and related to the incidence of SARS-CoV-2 infections. For all initial ethics applications, the median time to a positive ethics vote was less than two weeks and 30 of these study sites (65%) joined NAPKON within less than three weeks each. Electronic instead of postal ethics submission (9.5 days (Q1: 5.75, Q3: 17) vs. 14 days (Q1: 11, Q3: 26), p value = 0.01) and adoption of the primary ethics vote significantly accelerated the ethics application process. Each study center enrolled a median of 37 patients during the 14-month observation period, with large differences depending on the health sector. We found a positive correlation between recruitment performance and COVID-19 incidence as well as hospitalization incidence. Our analysis highlighted the challenges and opportunities of the federated system in Germany. Digital ethics application tools, adoption of a primary ethics vote and standardized formal requirements lead to harmonized and thus faster study initiation processes during a pandemic.
Abstract:
With the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), global researchers were confronted with major challenges. The German National Pandemic Cohort Network (NAPKON) was launched in fall 2020 to effectively leverage resources and bundle research activities in the fight against the coronavirus disease 2019 (COVID-19) pandemic. We analyzed the setup phase of NAPKON as an example for multicenter studies in Germany, highlighting challenges and optimization potential in connecting 59 university and nonuniversity study sites. We examined the ethics application process of 121 ethics submissions considering durations, annotations, and outcomes. Study site activation and recruitment processes were investigated and related to the incidence of SARS-CoV-2 infections. For all initial ethics applications, the median time to a positive ethics vote was less than two weeks and 30 of these study sites (65%) joined NAPKON within less than three weeks each. Electronic instead of postal ethics submission (9.5 days (Q1: 5.75, Q3: 17) vs. 14 days (Q1: 11, Q3: 26), p value = 0.01) and adoption of the primary ethics vote significantly accelerated the ethics application process. Each study center enrolled a median of 37 patients during the 14-month observation period, with large differences depending on the health sector. We found a positive correlation between recruitment performance and COVID-19 incidence as well as hospitalization incidence. Our analysis highlighted the challenges and opportunities of the federated system in Germany. Digital ethics application tools, adoption of a primary ethics vote and standardized formal requirements lead to harmonized and thus faster study initiation processes during a pandemic.
[en]
K. Schulze-Wundling,
P. F. Ottensmeyer,
K. M. Meyer-Schlinkmann,
M. Deckena,
S. Krüger,
S. Schlinkert,
A. Budde,
D. Münstermann,
N. Töpfner,
A. Petersmann,
M. Nauck,
A. Karch,
B. Lange,
S. Blaschke,
C. Tiemann and
H. Streeck,
"Immunity against SARS-CoV-2 in the German population",
Dtsch. Arztebl. Int.,
vol. 120,
no. 19,
pp. 337—344,
Mai
2023.
Abstract:
BACKGROUND: Early during the SARS-CoV-2 pandemic, national population-based seroprevalence surveys were conducted in some countries; however, this was not done in Germany. In particular, no seroprevalence surveys were planned for the summer of 2022. In the context of the IMMUNEBRIDGE project, the GUIDE study was carried out to estimate seroprevalence on the national and regional levels. METHODS: To obtain an overview of the population-wide immunity against SARS-CoV-2 among adults in Germany that would be as statistically robust as possible, serological tests were carried out using self-sampling dried blood spot cards in conjunction with surveys, one by telephone and one online. Blood samples were analyzed for the presence of antibodies to the S and N antigens of SARS-CoV-2. RESULTS: Among the 15 932 participants, antibodies to the S antigen were detected in 95.7%, and to the N antigen in 44.4%. In the higher-risk age groups of persons aged 65 and above and persons aged 80 and above, anti-S antibodies were found in 97,4% and 98.8%, respectively. Distinct regional differences in the distribution of anti-S and anti-N antibodies emerged. Immunity gaps were found both regionally and in particular subgroups of the population. High anti-N antibody levels were especially common in eastern German states, and high anti-S antibody levels in western German states. CONCLUSION: These findings indicate that a large percentage of the adult German population has formed antibodies against the SARS-CoV-2 virus. This will markedly lower the probability of an overburdening of the health care system by hospitalization and high occupancy of intensive care units due to future SARS-CoV-2 waves, depending on the viral characteristics of then prevailing variants.
| DOI: | https://doi.org/10.3238/arztebl.m2023.0072 |
Abstract:
BACKGROUND: Early during the SARS-CoV-2 pandemic, national population-based seroprevalence surveys were conducted in some countries; however, this was not done in Germany. In particular, no seroprevalence surveys were planned for the summer of 2022. In the context of the IMMUNEBRIDGE project, the GUIDE study was carried out to estimate seroprevalence on the national and regional levels. METHODS: To obtain an overview of the population-wide immunity against SARS-CoV-2 among adults in Germany that would be as statistically robust as possible, serological tests were carried out using self-sampling dried blood spot cards in conjunction with surveys, one by telephone and one online. Blood samples were analyzed for the presence of antibodies to the S and N antigens of SARS-CoV-2. RESULTS: Among the 15 932 participants, antibodies to the S antigen were detected in 95.7%, and to the N antigen in 44.4%. In the higher-risk age groups of persons aged 65 and above and persons aged 80 and above, anti-S antibodies were found in 97,4% and 98.8%, respectively. Distinct regional differences in the distribution of anti-S and anti-N antibodies emerged. Immunity gaps were found both regionally and in particular subgroups of the population. High anti-N antibody levels were especially common in eastern German states, and high anti-S antibody levels in western German states. CONCLUSION: These findings indicate that a large percentage of the adult German population has formed antibodies against the SARS-CoV-2 virus. This will markedly lower the probability of an overburdening of the health care system by hospitalization and high occupancy of intensive care units due to future SARS-CoV-2 waves, depending on the viral characteristics of then prevailing variants.
[en]
K. O. Yusuf,
I. Chaplinskaya-Sobol,
A. Schoneberg,
S. Hanß,
H. Valentin,
B. Lorenz-Depiereux,
S. Hansch,
K. Fiedler,
M. Scherer,
S. Sikdar,
O. Miljukov,
J. Reese,
P. Wagner,
I. Bröhl,
R. Geisler,
J. J. Vehreschild,
S. Blaschke,
C. Bellinghausen,
M. Milovanovic and
D. Krefting,
"Impact of clinical study implementation on data quality
assessments - using contradictions within interdependent health
data items as a pilot indicator",
Stud. Health Technol. Inform.,
vol. 307,
pp. 152—158,
Sep.
2023.
Abstract:
INTRODUCTION: Contradiction is a relevant data quality indicator to evaluate the plausibility of interdependent health data items. However, while contradiction assessment is achieved using domain-established contradictory dependencies, recent studies have shown the necessity for additional requirements to reach conclusive contradiction findings. For example, the oral or rectal methods used in measuring the body temperature will influence the thresholds of fever definition. The availability of this required information as explicit data items must be guaranteed during study design. In this work, we investigate the impact of activities related to study database implementation on contradiction assessment from two perspectives including: 1) additionally required metadata and 2) implementation of checks within electronic case report forms to prevent contradictory data entries. METHODS: Relevant information (timestamps, measurement methods, units, and interdependency rules) required for contradiction checks are identified. Scores are assigned to these parameters and two different studies are evaluated based on the fulfillment of the requirements by two selected interdependent data item sets. RESULTS: None of the studies have fulfilled all requirements. While timestamps and measurement units are found, missing information about measurement methods may impede conclusive contradiction assessment. Implemented checks are only found if data are directly entered. DISCUSSION: Conclusive contradiction assessment typically requires metadata in the context of captured data items. Consideration during study design and implementation of data capture systems may support better data quality in studies and could be further adopted in primary health information systems to enhance clinical anamnestic documentation.
| DOI: | 10.3233/SHTI230707 |
Abstract:
INTRODUCTION: Contradiction is a relevant data quality indicator to evaluate the plausibility of interdependent health data items. However, while contradiction assessment is achieved using domain-established contradictory dependencies, recent studies have shown the necessity for additional requirements to reach conclusive contradiction findings. For example, the oral or rectal methods used in measuring the body temperature will influence the thresholds of fever definition. The availability of this required information as explicit data items must be guaranteed during study design. In this work, we investigate the impact of activities related to study database implementation on contradiction assessment from two perspectives including: 1) additionally required metadata and 2) implementation of checks within electronic case report forms to prevent contradictory data entries. METHODS: Relevant information (timestamps, measurement methods, units, and interdependency rules) required for contradiction checks are identified. Scores are assigned to these parameters and two different studies are evaluated based on the fulfillment of the requirements by two selected interdependent data item sets. RESULTS: None of the studies have fulfilled all requirements. While timestamps and measurement units are found, missing information about measurement methods may impede conclusive contradiction assessment. Implemented checks are only found if data are directly entered. DISCUSSION: Conclusive contradiction assessment typically requires metadata in the context of captured data items. Consideration during study design and implementation of data capture systems may support better data quality in studies and could be further adopted in primary health information systems to enhance clinical anamnestic documentation.
[en]
E. Pappe,
R. Hammerich,
J. Saccomanno,
T. Sgarbossa,
A. Pohrt,
B. Schmidt,
C. Grah,
S. Eisenmann,
A. Holland,
S. Eggeling,
F. Stanzel,
M. Witzenrath and
R. Hübner,
"Impact of Coronavirus disease 2019 on hospital admissions,
health status, and behavioral changes of patients with COPD",
Chronic Obstr. Pulm. Dis.,
vol. 10,
no. 3,
pp. 211—223,
Jul.
2023.
COPD Foundation.
Abstract:
Introduction: Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of acquiring severe coronavirus disease 2019 (COVID-19), which is why self-isolation was recommended. However, long periods of social isolation, accompanied by limited access to health care systems, might influence the outcome of patients with severe COPD negatively. Methods: Data from COPD and pneumonia patients at Charité-Universit"atsmedizin Berlin and the volume of endoscopic lung volume reduction (ELVR) surgeries from the German Lung Emphysema Registry (Lungenemphysem Register e.V.) were analyzed from pre-pandemic (2012 to 2019) to the pandemic period (2020 and 2021). In addition, 52 patients with COPD Global initiative for chronic Obstructive Lung Disease (GOLD) stage 4 status included in the lung emphysema registry received questionnaires during lockdowns from June 2020 to April 2021. Results: Admissions and ventilation therapies administered to COPD patients significantly decreased during the COVID-19 pandemic. Likewise, there was a reduction in ELVR treatments and follow-ups registered in German emphysema centers. Mortality was slightly higher among patients hospitalized with COPD during the pandemic. Increasing proportions of COPD patients with GOLD stage 3 and GOLD stage 4 status reported behavioral changes and subjective feelings of increasing COPD symptoms the longer the lockdown lasted. However, COPD symptom questionnaires revealed stable COPD symptoms over the pandemic time period. Summary: This study reveals reduced COPD admissions and elective treatment procedures of COPD patients during the pandemic, but a slight increase in mortality among patients hospitalized with COPD, irrespective of COVID-19. Correspondingly, patients with severe COPD reported subjective deterioration of their health status, probably caused by their very strict compliance with lockdown measures.
| DOI: | 10.15326/jcopdf.2022.0383 |
Abstract:
Introduction: Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of acquiring severe coronavirus disease 2019 (COVID-19), which is why self-isolation was recommended. However, long periods of social isolation, accompanied by limited access to health care systems, might influence the outcome of patients with severe COPD negatively. Methods: Data from COPD and pneumonia patients at Charité-Universit"atsmedizin Berlin and the volume of endoscopic lung volume reduction (ELVR) surgeries from the German Lung Emphysema Registry (Lungenemphysem Register e.V.) were analyzed from pre-pandemic (2012 to 2019) to the pandemic period (2020 and 2021). In addition, 52 patients with COPD Global initiative for chronic Obstructive Lung Disease (GOLD) stage 4 status included in the lung emphysema registry received questionnaires during lockdowns from June 2020 to April 2021. Results: Admissions and ventilation therapies administered to COPD patients significantly decreased during the COVID-19 pandemic. Likewise, there was a reduction in ELVR treatments and follow-ups registered in German emphysema centers. Mortality was slightly higher among patients hospitalized with COPD during the pandemic. Increasing proportions of COPD patients with GOLD stage 3 and GOLD stage 4 status reported behavioral changes and subjective feelings of increasing COPD symptoms the longer the lockdown lasted. However, COPD symptom questionnaires revealed stable COPD symptoms over the pandemic time period. Summary: This study reveals reduced COPD admissions and elective treatment procedures of COPD patients during the pandemic, but a slight increase in mortality among patients hospitalized with COPD, irrespective of COVID-19. Correspondingly, patients with severe COPD reported subjective deterioration of their health status, probably caused by their very strict compliance with lockdown measures.
M. Granai,
V. Warm,
A. Vogelsberg,
J. Milla,
K. Greif,
U. Vogel,
T. Bakchoul,
P. Rosenberger,
L. Quintanilla-Martinez,
C. Schürch,
K. Klingel,
F. Fend and
H. Bösmüller,
"Impact of P-selectin-PSGL-1 Axis on Platelet-Endothelium-Leucocyte Interactions in Fatal COVID-19",
Laboratory Investigation; a Journal of Technical Methods and Pathology,
pp. 100179,
Mai
2023.
Abstract:
In critically ill SARS-CoV-2 infected patients, early leukocyte recruitment to the respiratory system was found to be orchestrated by leukocyte trafficking molecules accompanied by massive secretion of pro-inflammatory cytokines and hypercoagulability. Our study aimed to explore the interplay between leukocyte activation and pulmonary endothelium in different disease stages of fatal COVID-19. Our study comprised 10 COVID-19 post-mortem lung specimens and 20 control lung samples (5 ARDS, 2 viral pneumonia, 3 bacterial pneumonia, and 10 normal) which were stained for antigens representing the different steps of leucocyte migration: E-selectin, P-selectin, PSGL-1, ICAM1, VCAM1, and CD11b. Image analysis software QuPath was used for quantification of positive leukocytes (PSGL-1 and CD11b) and endothelium (E-selectin, P-selectin, ICAM1, VCAM1). Expression of IL-6 and IL-1ß was quantified by qRT-PCR. Expression of P-selectin and PSGL-1 was strongly increased in the COVID-19 cohort compared to all control groups (ratio =17,23, p\textless0,0001; ratio=2,75, p\textless0,0001 respectively). Importantly, P-selectin was found in endothelial cells and associated with aggregates of activated platelets adherent to the endothelial surface in COVID-19 cases. In addition, PSGL-1 staining disclosed positive perivascular leucocyte cuffs, reflecting capillaritis. Moreover, CD11b showed a strongly increased positivity in COVID-19 compared to all controls (ratio=2,89; p=0,0002), indicating a proinflammatory immune microenvironment. Of note, CD11b exhibited distinct staining patterns at different stages of COVID-19 disease. Only in cases with very short disease course, high levels of IL-1ß and IL-6 mRNA were observed in lung tissue. The striking upregulation of PSGL-1 and P-selectin reflects the activation of this receptor-ligand pair in COVID-19, increasing the efficiency of initial leucocyte recruitment, thus promoting tissue damage and immunothrombosis. Our results show that endothelial activation and unbalanced leukocyte migration play a central role in COVID-19 involving the P-selectin-PSGL-1 axis.
| DOI: | 10.1016/j.labinv.2023.100179 |
| Datei: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10202465/ |
Abstract:
In critically ill SARS-CoV-2 infected patients, early leukocyte recruitment to the respiratory system was found to be orchestrated by leukocyte trafficking molecules accompanied by massive secretion of pro-inflammatory cytokines and hypercoagulability. Our study aimed to explore the interplay between leukocyte activation and pulmonary endothelium in different disease stages of fatal COVID-19. Our study comprised 10 COVID-19 post-mortem lung specimens and 20 control lung samples (5 ARDS, 2 viral pneumonia, 3 bacterial pneumonia, and 10 normal) which were stained for antigens representing the different steps of leucocyte migration: E-selectin, P-selectin, PSGL-1, ICAM1, VCAM1, and CD11b. Image analysis software QuPath was used for quantification of positive leukocytes (PSGL-1 and CD11b) and endothelium (E-selectin, P-selectin, ICAM1, VCAM1). Expression of IL-6 and IL-1ß was quantified by qRT-PCR. Expression of P-selectin and PSGL-1 was strongly increased in the COVID-19 cohort compared to all control groups (ratio =17,23, p\textless0,0001; ratio=2,75, p\textless0,0001 respectively). Importantly, P-selectin was found in endothelial cells and associated with aggregates of activated platelets adherent to the endothelial surface in COVID-19 cases. In addition, PSGL-1 staining disclosed positive perivascular leucocyte cuffs, reflecting capillaritis. Moreover, CD11b showed a strongly increased positivity in COVID-19 compared to all controls (ratio=2,89; p=0,0002), indicating a proinflammatory immune microenvironment. Of note, CD11b exhibited distinct staining patterns at different stages of COVID-19 disease. Only in cases with very short disease course, high levels of IL-1ß and IL-6 mRNA were observed in lung tissue. The striking upregulation of PSGL-1 and P-selectin reflects the activation of this receptor-ligand pair in COVID-19, increasing the efficiency of initial leucocyte recruitment, thus promoting tissue damage and immunothrombosis. Our results show that endothelial activation and unbalanced leukocyte migration play a central role in COVID-19 involving the P-selectin-PSGL-1 axis.
[en]
Z. Liu,
C. Hollmann,
S. Kalanidhi,
A. Grothey,
S. Keating,
I. Mena-Palomo,
S. Lamer,
A. Schlosser,
A. Kaiping,
C. Scheller,
F. Sotzny,
A. Horn,
C. Nürnberger,
V. Cejka,
B. Afshar,
T. Bahmer,
S. Schreiber,
J. J. Vehreschild,
O. Miljukov,
C. Schäfer,
L. Kretzler,
T. Keil,
J. Reese,
F. A. Eichner,
L. Schmidbauer,
P. U. Heuschmann,
S. Störk,
C. Morbach,
G. Riemekasten,
N. Beyersdorf,
C. Scheibenbogen,
R. K. Naviaux,
M. Williams,
M. E. Ariza and
B. K. Prusty,
"Increased circulating fibronectin, depletion of natural IgM and
heightened EBV, HSV-1 reactivation in ME/CFS and long
COVID",
medRxiv,
vol. Online ahead of print,
Jun.
2023.
Abstract:
Myalgic Encephalomyelitis/ Chronic Fatigue syndrome (ME/CFS) is a complex, debilitating, long-term illness without a diagnostic biomarker. ME/CFS patients share overlapping symptoms with long COVID patients, an observation which has strengthened the infectious origin hypothesis of ME/CFS. However, the exact sequence of events leading to disease development is largely unknown for both clinical conditions. Here we show antibody response to herpesvirus dUTPases, particularly to that of Epstein-Barr virus (EBV) and HSV-1, increased circulating fibronectin (FN1) levels in serum and depletion of natural IgM against fibronectin ((n)IgM-FN1) are common factors for both severe ME/CFS and long COVID. We provide evidence for herpesvirus dUTPases-mediated alterations in host cell cytoskeleton, mitochondrial dysfunction and OXPHOS. Our data show altered active immune complexes, immunoglobulin-mediated mitochondrial fragmentation as well as adaptive IgM production in ME/CFS patients. Our findings provide mechanistic insight into both ME/CFS and long COVID development. Finding of increased circulating FN1 and depletion of (n)IgM-FN1 as a biomarker for the severity of both ME/CFS and long COVID has an immediate implication in diagnostics and development of treatment modalities.
| DOI: | 10.1101/2023.06.23.23291827 |
| Pubmed: | 37425897 |
Abstract:
Myalgic Encephalomyelitis/ Chronic Fatigue syndrome (ME/CFS) is a complex, debilitating, long-term illness without a diagnostic biomarker. ME/CFS patients share overlapping symptoms with long COVID patients, an observation which has strengthened the infectious origin hypothesis of ME/CFS. However, the exact sequence of events leading to disease development is largely unknown for both clinical conditions. Here we show antibody response to herpesvirus dUTPases, particularly to that of Epstein-Barr virus (EBV) and HSV-1, increased circulating fibronectin (FN1) levels in serum and depletion of natural IgM against fibronectin ((n)IgM-FN1) are common factors for both severe ME/CFS and long COVID. We provide evidence for herpesvirus dUTPases-mediated alterations in host cell cytoskeleton, mitochondrial dysfunction and OXPHOS. Our data show altered active immune complexes, immunoglobulin-mediated mitochondrial fragmentation as well as adaptive IgM production in ME/CFS patients. Our findings provide mechanistic insight into both ME/CFS and long COVID development. Finding of increased circulating FN1 and depletion of (n)IgM-FN1 as a biomarker for the severity of both ME/CFS and long COVID has an immediate implication in diagnostics and development of treatment modalities.
[en]
G. Lichtner,
T. Haese,
S. Brose,
L. Röhrig,
L. Lysyakova,
S. Rudolph,
M. Uebe,
J. Sass,
A. Bartschke,
D. Hillus,
F. Kurth,
L. E. Sander,
F. Eckart,
N. Toepfner,
R. Berner,
A. Frey,
M. Dörr,
J. J. Vehreschild,
C. Kalle and
S. Thun,
"Interoperable, domain-specific extensions for the German Corona Consensus (GECCO) COVID-19 research data set using an interdisciplinary, consensus-based workflow: Data set development study",
JMIR Med. Inform.,
vol. 11,
pp. e45496,
Jul.
2023.
Abstract:
Background: The COVID-19 pandemic has spurred large-scale, interinstitutional research efforts. To enable these efforts, researchers must agree on data set definitions that not only cover all elements relevant to the respective medical specialty but also are syntactically and semantically interoperable. Therefore, the German Corona Consensus (GECCO) data set was developed as a harmonized, interoperable collection of the most relevant data elements for COVID-19-related patient research. As the GECCO data set is a compact core data set comprising data across all medical fields, the focused research within particular medical domains demands the definition of extension modules that include data elements that are the most relevant to the research performed in those individual medical specialties. Objective: We aimed to (1) specify a workflow for the development of interoperable data set definitions that involves close collaboration between medical experts and information scientists and (2) apply the workflow to develop data set definitions that include data elements that are the most relevant to COVID-19-related patient research regarding immunization, pediatrics, and cardiology. Methods: We developed a workflow to create data set definitions that were (1) content-wise as relevant as possible to a specific field of study and (2) universally usable across computer systems, institutions, and countries (ie, interoperable). We then gathered medical experts from 3 specialties-infectious diseases (with a focus on immunization), pediatrics, and cardiology-to select data elements that were the most relevant to COVID-19-related patient research in the respective specialty. We mapped the data elements to international standardized vocabularies and created data exchange specifications, using Health Level Seven International (HL7) Fast Healthcare Interoperability Resources (FHIR). All steps were performed in close interdisciplinary collaboration with medical domain experts and medical information specialists. Profiles and vocabulary mappings were syntactically and semantically validated in a 2-stage process. Results: We created GECCO extension modules for the immunization, pediatrics, and cardiology domains according to pandemic-related requests. The data elements included in each module were selected, according to the developed consensus-based workflow, by medical experts from these specialties to ensure that the contents aligned with their research needs. We defined data set specifications for 48 immunization, 150 pediatrics, and 52 cardiology data elements that complement the GECCO core data set. We created and published implementation guides, example implementations, and data set annotations for each extension module. Conclusions: The GECCO extension modules, which contain data elements that are the most relevant to COVID-19-related patient research on infectious diseases (with a focus on immunization), pediatrics, and cardiology, were defined in an interdisciplinary, iterative, consensus-based workflow that may serve as a blueprint for developing further data set definitions. The GECCO extension modules provide standardized and harmonized definitions of specialty-related data sets that can help enable interinstitutional and cross-country COVID-19 research in these specialties.
| DOI: | 10.2196/45496 |
| Pubmed: | 37490312 |
Abstract:
Background: The COVID-19 pandemic has spurred large-scale, interinstitutional research efforts. To enable these efforts, researchers must agree on data set definitions that not only cover all elements relevant to the respective medical specialty but also are syntactically and semantically interoperable. Therefore, the German Corona Consensus (GECCO) data set was developed as a harmonized, interoperable collection of the most relevant data elements for COVID-19-related patient research. As the GECCO data set is a compact core data set comprising data across all medical fields, the focused research within particular medical domains demands the definition of extension modules that include data elements that are the most relevant to the research performed in those individual medical specialties. Objective: We aimed to (1) specify a workflow for the development of interoperable data set definitions that involves close collaboration between medical experts and information scientists and (2) apply the workflow to develop data set definitions that include data elements that are the most relevant to COVID-19-related patient research regarding immunization, pediatrics, and cardiology. Methods: We developed a workflow to create data set definitions that were (1) content-wise as relevant as possible to a specific field of study and (2) universally usable across computer systems, institutions, and countries (ie, interoperable). We then gathered medical experts from 3 specialties-infectious diseases (with a focus on immunization), pediatrics, and cardiology-to select data elements that were the most relevant to COVID-19-related patient research in the respective specialty. We mapped the data elements to international standardized vocabularies and created data exchange specifications, using Health Level Seven International (HL7) Fast Healthcare Interoperability Resources (FHIR). All steps were performed in close interdisciplinary collaboration with medical domain experts and medical information specialists. Profiles and vocabulary mappings were syntactically and semantically validated in a 2-stage process. Results: We created GECCO extension modules for the immunization, pediatrics, and cardiology domains according to pandemic-related requests. The data elements included in each module were selected, according to the developed consensus-based workflow, by medical experts from these specialties to ensure that the contents aligned with their research needs. We defined data set specifications for 48 immunization, 150 pediatrics, and 52 cardiology data elements that complement the GECCO core data set. We created and published implementation guides, example implementations, and data set annotations for each extension module. Conclusions: The GECCO extension modules, which contain data elements that are the most relevant to COVID-19-related patient research on infectious diseases (with a focus on immunization), pediatrics, and cardiology, were defined in an interdisciplinary, iterative, consensus-based workflow that may serve as a blueprint for developing further data set definitions. The GECCO extension modules provide standardized and harmonized definitions of specialty-related data sets that can help enable interinstitutional and cross-country COVID-19 research in these specialties.
S. Sikdar,
"Krankheitskostenanalyse der stationären Behandlung von COVID-19 Patient:innen.",
Poster KIT Kongress 2023, Leipzig,
2023.
[eng]
A. T. Azeke,
J. Schädler,
B. Ondruschka,
S. Steurer,
D. Möbius and
A. Fitzek,
"Minimally Invasive Tissue Sampling via Post Mortem Ultrasound: A Feasible Tool (Not Only) in Infectious Diseases-A Case Report",
Diagnostics (Basel, Switzerland),
vol. 13,
no. 16,
pp. 2643,
Aug.
2023.
Abstract:
In the past years the number of hospital autopsies have declined steadily, becoming almost excluded from medical training. Medicolegal (forensic) autopsies account for almost all autopsies, whereas hospital autopsies are becoming increasingly rare. Minimally invasive tissue sampling (MITS) using post mortem ultrasound offers the opportunity to increase the number of post mortem examinations in a clinical and even forensic context. MITS is a needle-based post mortem procedure that uses (radiological) imaging techniques to examine major organs of the body, acquire tissue samples and aspirate fluid from the body cavities or hollow organs. In this study, MITS was used to determine the presence of other co-existing diseases in a deceased infected 97-year-old woman with severe acute respiratory syndrome coronavirus 2. The examination of her body was carried out using ultrasound as an imaging tool and to gather ultrasound-guided biopsies as conventional autopsy was rejected by the next of kin. Ultrasound and histology identified an intravesical mass leading to an obstruction of the urinary outlet resulting in bilateral hydronephrosis and purulent pyelonephritis, which was unknown during her lifetime. Histopathological examination revealed the tumor mass to be a squamous cell carcinoma. This study has shown that MITS can be used to determine the cause of death and the presence of concomitant diseases in the infectious deceased.
| DOI: | 10.3390/diagnostics13162643 |
| Datei: | https://doi.org/10.3390%2Fdiagnostics13162643 |
Abstract:
In the past years the number of hospital autopsies have declined steadily, becoming almost excluded from medical training. Medicolegal (forensic) autopsies account for almost all autopsies, whereas hospital autopsies are becoming increasingly rare. Minimally invasive tissue sampling (MITS) using post mortem ultrasound offers the opportunity to increase the number of post mortem examinations in a clinical and even forensic context. MITS is a needle-based post mortem procedure that uses (radiological) imaging techniques to examine major organs of the body, acquire tissue samples and aspirate fluid from the body cavities or hollow organs. In this study, MITS was used to determine the presence of other co-existing diseases in a deceased infected 97-year-old woman with severe acute respiratory syndrome coronavirus 2. The examination of her body was carried out using ultrasound as an imaging tool and to gather ultrasound-guided biopsies as conventional autopsy was rejected by the next of kin. Ultrasound and histology identified an intravesical mass leading to an obstruction of the urinary outlet resulting in bilateral hydronephrosis and purulent pyelonephritis, which was unknown during her lifetime. Histopathological examination revealed the tumor mass to be a squamous cell carcinoma. This study has shown that MITS can be used to determine the cause of death and the presence of concomitant diseases in the infectious deceased.
J. Kottlors,
P. Fervers,
S. Geißen,
R. Gertz,
J. Bremm,
M. Rinneburger,
M. Weisthoff,
R. Shahzad,
D. Maintz and
T. Persigehl,
"Morphological appearance of the B.1.1.7 mutation of the novel coronavirus 2 (SARS-CoV-2) in chest CT",
Quant Imaging Med Surg,
vol. 13,
no. 2,
pp. 1058—70,
2023.
[eng]
F. Heinrich,
T. Huter,
S. Mertens,
P. Lange,
J. Vering,
A. Heinemann,
D. S. Nörz,
A. Hoffmann,
M. Aepfelbacher,
B. Ondruschka,
S. Krasemann and
M. Lütgehetmann,
"New Postmortem Perspective on Emerging SARS-CoV-2 Variants of Concern, Germany",
Emerging Infectious Diseases,
vol. 29,
no. 3,
pp. 652—656,
Mä.
2023.
Abstract:
We performed autopsies on persons in Germany who died from COVID-19 and observed higher nasopharyngeal SARS-CoV-2 viral loads for variants of concern (VOC) compared with non-VOC lineages. Pulmonary inflammation and damage appeared higher in non-VOC than VOC lineages until adjusted for vaccination status, suggesting COVID-19 vaccination may mitigate pulmonary damage.
| DOI: | 10.3201/eid2903.221297 |
Abstract:
We performed autopsies on persons in Germany who died from COVID-19 and observed higher nasopharyngeal SARS-CoV-2 viral loads for variants of concern (VOC) compared with non-VOC lineages. Pulmonary inflammation and damage appeared higher in non-VOC than VOC lineages until adjusted for vaccination status, suggesting COVID-19 vaccination may mitigate pulmonary damage.
L. Schmidbauer,
C. Nürnberger,
C. Fiessler,
K. Franzpötter,
J. Haug,
F. Haug,
A. Hermes,
S. Jiru-Hillmann,
O. Miljukov,
A. Ruß,
J. J. Vehreschild,
M. Krawczak,
M. Witzenrath,
W. Lieb,
S. Schmidt,
J. Reese,
P. Heuschmann and
C. Bauer,
"NUKLEUS – NUM Klinische Epidemiologie- und Studienplattform",
Poster NAPKON Vention 2023, Frankfurt,
2023.
L. Schmidbauer,
C. Nürnberger,
C. Fiessler,
K. Franzpötter,
F. Haug,
J. Haug,
A. Hermes,
S. Jiru-Hillmann,
K. Günther,
O. Miljukov,
A. Ruß,
J. J. Vehreschild,
M. Krawczak,
M. Witzenrath,
W. Lieb,
M. Rose,
S. Schmidt,
W. Hoffmann,
J. Schmitt,
P. Ihle,
J. Reese and
P. U. Heuschmann,
"NUKLEUS – NUM Klinische Epidemiologie- und Studienplattform Epidemiology Core Unit (ECU)",
Poster DGEpi 2023, Würzburg,
2023.
M. Hoffmann,
L. R. Wong,
P. Arora,
L. Zhang,
C. Rocha,
A. Odle,
I. Nehlmeier,
A. Kempf,
A. Richter,
N. J. Halwe,
J. Schön,
L. Ulrich,
D. Hoffmann,
M. Beer,
C. Drosten,
S. Perlman and
S. Pöhlmann,
"Omicron subvariant BA.5 efficiently infects lung cells",
Nature communications,
vol. 14,
no. 1,
pp. 3500,
2023.
Abstract:
The SARS-CoV-2 Omicron subvariants BA.1 and BA.2 exhibit reduced lung cell infection relative to previously circulating SARS-CoV-2 variants, which may account for their reduced pathogenicity. However, it is unclear whether lung cell infection by BA.5, which displaced these variants, remains attenuated. Here, we show that the spike (S) protein of BA.5 exhibits increased cleavage at the S1/S2 site and drives cell-cell fusion and lung cell entry with higher efficiency than its counterparts from BA.1 and BA.2. Increased lung cell entry depends on mutation H69\textgreekD/V70\textgreekD and is associated with efficient replication of BA.5 in cultured lung cells. Further, BA.5 replicates in the lungs of female Balb/c mice and the nasal cavity of female ferrets with much higher efficiency than BA.1. These results suggest that BA.5 has acquired the ability to efficiently infect lung cells, a prerequisite for causing severe disease, suggesting that evolution of Omicron subvariants can result in partial loss of attenuation.
| DOI: | 10.1038/s41467-023-39147-4 |
Abstract:
The SARS-CoV-2 Omicron subvariants BA.1 and BA.2 exhibit reduced lung cell infection relative to previously circulating SARS-CoV-2 variants, which may account for their reduced pathogenicity. However, it is unclear whether lung cell infection by BA.5, which displaced these variants, remains attenuated. Here, we show that the spike (S) protein of BA.5 exhibits increased cleavage at the S1/S2 site and drives cell-cell fusion and lung cell entry with higher efficiency than its counterparts from BA.1 and BA.2. Increased lung cell entry depends on mutation H69\textgreekD/V70\textgreekD and is associated with efficient replication of BA.5 in cultured lung cells. Further, BA.5 replicates in the lungs of female Balb/c mice and the nasal cavity of female ferrets with much higher efficiency than BA.1. These results suggest that BA.5 has acquired the ability to efficiently infect lung cells, a prerequisite for causing severe disease, suggesting that evolution of Omicron subvariants can result in partial loss of attenuation.
[en]
Y. Shi,
R. Strobl,
C. Apfelbacher,
T. Bahmer,
R. Geisler,
P. Heuschmann,
A. Horn,
H. Hoven,
T. Keil,
M. Krawczak,
L. Krist,
C. Lemhöfer,
W. Lieb,
B. Lorenz-Depiereux,
R. Mikolajczyk,
F. A. Montellano,
J. P. Reese,
S. Schreiber,
N. Skoetz,
S. Störk,
J. J. Vehreschild,
M. Witzenrath,
E. Grill and
NAPKON Study Group,
"Persistent symptoms and risk factors predicting prolonged time to symptom-free after SARS‑CoV‑2 infection: an analysis of the baseline examination of the German COVIDOM/NAPKON-POP cohort",
Infection,
vol. 51,
no. 6,
pp. 1679–1694,
Mai
2023.
Abstract:
PURPOSE: We aimed to assess symptoms in patients after SARS-CoV-2 infection and to identify factors predicting prolonged time to symptom-free. METHODS: COVIDOM/NAPKON-POP is a population-based prospective cohort of adults whose first on-site visits were scheduled $\geq$ 6 months after a positive SARS-CoV-2 PCR test. Retrospective data including self-reported symptoms and time to symptom-free were collected during the survey before a site visit. In the survival analyses, being symptom-free served as the event and time to be symptom-free as the time variable. Data were visualized with Kaplan-Meier curves, differences were tested with log-rank tests. A stratified Cox proportional hazard model was used to estimate adjusted hazard ratios (aHRs) of predictors, with aHR < 1 indicating a longer time to symptom-free. RESULTS: Of 1175 symptomatic participants included in the present analysis, 636 (54.1%) reported persistent symptoms after 280 days (SD 68) post infection. 25% of participants were free from symptoms after 18 days [quartiles: 14, 21]. Factors associated with prolonged time to symptom-free were age 49-59 years compared to < 49 years (aHR 0.70, 95% CI 0.56-0.87), female sex (aHR 0.78, 95% CI 0.65-0.93), lower educational level (aHR 0.77, 95% CI 0.64-0.93), living with a partner (aHR 0.81, 95% CI 0.66-0.99), low resilience (aHR 0.65, 95% CI 0.47-0.90), steroid treatment (aHR 0.22, 95% CI 0.05-0.90) and no medication (aHR 0.74, 95% CI 0.62-0.89) during acute infection. CONCLUSION: In the studied population, COVID-19 symptoms had resolved in one-quarter of participants within 18 days, and in 34.5% within 28 days. Over half of the participants reported COVID-19-related symptoms 9 months after infection. Symptom persistence was predominantly determined by participant's characteristics that are difficult to modify.
| DOI: | 10.1007/s15010-023-02043-6 |
| Pubmed: | 37231313 |
Abstract:
PURPOSE: We aimed to assess symptoms in patients after SARS-CoV-2 infection and to identify factors predicting prolonged time to symptom-free. METHODS: COVIDOM/NAPKON-POP is a population-based prospective cohort of adults whose first on-site visits were scheduled $\geq$ 6 months after a positive SARS-CoV-2 PCR test. Retrospective data including self-reported symptoms and time to symptom-free were collected during the survey before a site visit. In the survival analyses, being symptom-free served as the event and time to be symptom-free as the time variable. Data were visualized with Kaplan-Meier curves, differences were tested with log-rank tests. A stratified Cox proportional hazard model was used to estimate adjusted hazard ratios (aHRs) of predictors, with aHR < 1 indicating a longer time to symptom-free. RESULTS: Of 1175 symptomatic participants included in the present analysis, 636 (54.1%) reported persistent symptoms after 280 days (SD 68) post infection. 25% of participants were free from symptoms after 18 days [quartiles: 14, 21]. Factors associated with prolonged time to symptom-free were age 49-59 years compared to < 49 years (aHR 0.70, 95% CI 0.56-0.87), female sex (aHR 0.78, 95% CI 0.65-0.93), lower educational level (aHR 0.77, 95% CI 0.64-0.93), living with a partner (aHR 0.81, 95% CI 0.66-0.99), low resilience (aHR 0.65, 95% CI 0.47-0.90), steroid treatment (aHR 0.22, 95% CI 0.05-0.90) and no medication (aHR 0.74, 95% CI 0.62-0.89) during acute infection. CONCLUSION: In the studied population, COVID-19 symptoms had resolved in one-quarter of participants within 18 days, and in 34.5% within 28 days. Over half of the participants reported COVID-19-related symptoms 9 months after infection. Symptom persistence was predominantly determined by participant's characteristics that are difficult to modify.
[en]
S. Winkelmann,
A. Korth,
B. Voss,
M. A. Nasr,
N. Behrend,
A. Pudszuhn,
V. M. Hofmann,
P. Schendzielorz,
C. Maetzler,
A. Hermes,
C. Borzikowsky,
T. Bahmer,
W. Lieb,
S. Schreiber,
S. Störk,
F. A. Montellano,
M. Witzenrath,
T. Keil,
M. Krawczak,
M. Laudien and
On Behalf Of The Napkon Study Group,
"Persisting chemosensory dysfunction in COVID-19 - a cross-sectional population-based survey",
Rhinology,
vol. 61,
no. 1,
pp. 12—23,
Feb.
2023.
Stichting Nase.
Abstract:
BACKGROUND: Chemosensory dysfunction (CD) has been reported as a common symptom of SARS-CoV-2 infection, but it is not well understood whether and for how long changes of smell, taste and chemesthesis persist in infected individuals. METHODOLOGY: Unselected adult residents of the German federal state of Schleswig-Holstein with Polymerase Chain Reaction (PCR)-test-confirmed SARS-CoV-2 infection were invited to participate in this large cross-sectional study. Data on the medical history and subjective chemosensory function of participants were obtained through questionnaires and visual analogue scales (VAS). Olfactory function (OF) was objectified with the Sniffin Sticks test (SST), including threshold (T), discrimination (D) and identification (I) test as well as summarized TDI score, and compared to that in healthy controls. Gustatory function (GF) was evaluated with the suprathreshold taste strips (TS) test, and trigeminal function was tested with an ampoule containing ammonia. RESULTS: Between November 2020 and June 2021, 667 infected individuals (mean age: 48.2 years) were examined 9.1 months, on average, after positive PCR testing. Of these, 45.6% had persisting subjective olfactory dysfunction (OD), 36.2% had subjective gustatory dysfunction (GD). Tested OD, tested GD and impaired trigeminal function were observed in 34.6%, 7.3% and 1.8% of participants, respectively. The mean TDI score of participants was significantly lower compared to healthy subjects. Significant associations were observed between subjective OD and GD, and between tested OD and GD. CONCLUSION: Nine months after SARS-CoV-2 infection, OD prevalence is significantly increased among infected members of the general population. Therefore, OD should be included in the list of symptoms collectively defining Long-COVID.
| DOI: | 10.4193/Rhin22.176 |
Abstract:
BACKGROUND: Chemosensory dysfunction (CD) has been reported as a common symptom of SARS-CoV-2 infection, but it is not well understood whether and for how long changes of smell, taste and chemesthesis persist in infected individuals. METHODOLOGY: Unselected adult residents of the German federal state of Schleswig-Holstein with Polymerase Chain Reaction (PCR)-test-confirmed SARS-CoV-2 infection were invited to participate in this large cross-sectional study. Data on the medical history and subjective chemosensory function of participants were obtained through questionnaires and visual analogue scales (VAS). Olfactory function (OF) was objectified with the Sniffin Sticks test (SST), including threshold (T), discrimination (D) and identification (I) test as well as summarized TDI score, and compared to that in healthy controls. Gustatory function (GF) was evaluated with the suprathreshold taste strips (TS) test, and trigeminal function was tested with an ampoule containing ammonia. RESULTS: Between November 2020 and June 2021, 667 infected individuals (mean age: 48.2 years) were examined 9.1 months, on average, after positive PCR testing. Of these, 45.6% had persisting subjective olfactory dysfunction (OD), 36.2% had subjective gustatory dysfunction (GD). Tested OD, tested GD and impaired trigeminal function were observed in 34.6%, 7.3% and 1.8% of participants, respectively. The mean TDI score of participants was significantly lower compared to healthy subjects. Significant associations were observed between subjective OD and GD, and between tested OD and GD. CONCLUSION: Nine months after SARS-CoV-2 infection, OD prevalence is significantly increased among infected members of the general population. Therefore, OD should be included in the list of symptoms collectively defining Long-COVID.
P. Fervers,
F. Fervers,
M. Rinneburger,
M. Weisthoff,
J. Kottlors,
R. Reimer,
D. Zopfs,
E. Celik,
D. Maintz,
N. Große-Hokamp and
T. Persigehl,
"Physiological iodine uptake of the spine’s bone marrow in dual-energy computed tomography – using artificial intelligence to define reference values based on 678 CT examinations of 189 individuals",
Front Endocrinol (Lausanne),
vol. 14,
pp. 1365,
2023.
A. Surov,
H. Kardas,
G. Besutti,
M. Pellegrini,
M. Ottone,
M. Onur,
F. Atak,
A. Erdemir,
E. Hocaoglu,
Ö. Yıldız,
E. Inci,
E. Cingöz,
M. Cingöz,
M. Dursun,
İ. Korkmaz,
Ç. Orhan,
A. Strobel,
A. Wienke and
M. Pech,
"Prognostic Role of the Pectoralis Musculature in Patients with COVID-19. A Multicenter Study",
Acad Radiol,
vol. 30,
no. 1,
pp. 77—82,
2023.
| DOI: | 10.1016/j.acra.2022.05.003 |
[de]
M. Lutter,
I. Kniep,
B. Ondruschka and
A. Heinemann,
"Pulmonale Befunde in der postmortalen Computertomographie bei COVID-19-assoziierten Todesfällen",
Rechtsmedizin,
vol. 34,
pp. 17—23,
Dez.
2023.
Abstract:
Es gibt keine größeren Vergleichsstudien zu der Anwendbarkeit etablierter klinisch-diagnostischer Computertomographie (CT)-Kriterien für „Coronavirus Disease 2019“ (COVID-19)-Infektionen auf die postmortale Computertomographie (PMCT).
| DOI: | 10.1007/s00194-023-00667-4 |
| Datei: | https://doi.org/10.1007/s00194-023-00667-4 |
Abstract:
Es gibt keine größeren Vergleichsstudien zu der Anwendbarkeit etablierter klinisch-diagnostischer Computertomographie (CT)-Kriterien für „Coronavirus Disease 2019“ (COVID-19)-Infektionen auf die postmortale Computertomographie (PMCT).