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.
A. Kühnapfel,
K. Horn,
U. Klotz,
M. Kiehntopf,
M. Rosolowski,
M. Loeffler,
N. Suttorp,
M. Witzenrath and
M. Scholz,
"Genetic Regulation of Cytokine Response in Patients with Acute Community-Acquired Pneumonia",
Genes (Basel),
vol. 13,
no. 1,
pp. 111,
2022.
| DOI: | 10.3390/genes13010111 |
A. Kühnapfel,
K. Horn,
U. Klotz,
M. Kiehntopf,
M. Rosolowski,
M. Loeffler,
N. Suttorp,
M. Witzenrath and
M. Scholz,
"Genetic Regulation of Cytokine Response in Patients with Acute Community-Acquired Pneumonia. Genes (Basel).",
2022.
[en]
K. Hirschbühl,
T. Schaller,
B. Märkl,
R. Claus,
E. Sipos,
L. Rentschler,
A. Maccagno,
B. Grosser,
E. Kling,
M. Neidig,
T. Kröncke,
O. Spring,
G. Braun,
H. Bösmüller,
M. Seidl,
I. Esposito,
J. Pablik,
J. Hilsenbeck,
P. Boor,
M. Beer,
S. Dintner and
C. Wylezich,
"High viral loads: what drives fatal cases of COVID-19 in vaccinees? – an autopsy study",
Modern Pathology,
vol. 35,
no. 8,
pp. 1013—1021,
Aug.
2022.
Abstract:
The rate of SARS-CoV-2 infections in vaccinees has become a relevant serious issue. This study aimed to determine the causes of death, histological organ alteration, and viral spread in relation to demographic, clinical-pathological, viral variants, and vaccine types for deceased individuals with proven SARS-CoV-2 infection after vaccination who died between January and November 2021. Twenty-nine consecutively collected cases were analyzed and compared to 141 nonvaccinated control cases. Autopsies were performed on 16 partially and 13 fully vaccinated individuals. Most patients were elderly and suffered from several relevant comorbidities. Real-time RT-PCR (RT-qPCR) identified a significantly increased rate of generalized viral dissemination within organ systems in vaccinated cases versus nonvaccinated cases (45% vs. 16%, respectively; P = 0.008) mainly with Ct-values of higher than 25 in non-respiratory samples. However, vaccinated cases also showed high viral loads, reaching Ct-values below 10, especially in the upper airways and lungs. This was accompanied by high rates of pulmonal bacterial or mycotic superinfections and the occurrence of immunocompromising factors, such as malignancies, immunosuppressive drug intake, or decreased immunoglobulin levels. All these findings were particularly accentuated in partially vaccinated patients compared to fully vaccinated individuals. The virus dissemination observed in our case study may indicate that patients with an impaired immune system have a decreased ability to eliminate the virus. However, the potential role of antibody-dependent enhancement must also be ruled out in future studies. Fatal cases of COVID-19 in vaccinees were rare and often associated with severe comorbidities or other immunosuppressive conditions.
| DOI: | 10.1038/s41379-022-01069-9 |
| Datei: | https://www.nature.com/articles/s41379-022-01069-9 |
Abstract:
The rate of SARS-CoV-2 infections in vaccinees has become a relevant serious issue. This study aimed to determine the causes of death, histological organ alteration, and viral spread in relation to demographic, clinical-pathological, viral variants, and vaccine types for deceased individuals with proven SARS-CoV-2 infection after vaccination who died between January and November 2021. Twenty-nine consecutively collected cases were analyzed and compared to 141 nonvaccinated control cases. Autopsies were performed on 16 partially and 13 fully vaccinated individuals. Most patients were elderly and suffered from several relevant comorbidities. Real-time RT-PCR (RT-qPCR) identified a significantly increased rate of generalized viral dissemination within organ systems in vaccinated cases versus nonvaccinated cases (45% vs. 16%, respectively; P = 0.008) mainly with Ct-values of higher than 25 in non-respiratory samples. However, vaccinated cases also showed high viral loads, reaching Ct-values below 10, especially in the upper airways and lungs. This was accompanied by high rates of pulmonal bacterial or mycotic superinfections and the occurrence of immunocompromising factors, such as malignancies, immunosuppressive drug intake, or decreased immunoglobulin levels. All these findings were particularly accentuated in partially vaccinated patients compared to fully vaccinated individuals. The virus dissemination observed in our case study may indicate that patients with an impaired immune system have a decreased ability to eliminate the virus. However, the potential role of antibody-dependent enhancement must also be ruled out in future studies. Fatal cases of COVID-19 in vaccinees were rare and often associated with severe comorbidities or other immunosuppressive conditions.
R. Dannebaum,
P. Suwalski,
H. Asgharian,
Z. G. Du,
H. Lin,
J. Weiner,
M. Holtgrewe,
C. Thibeault,
M. Müller,
X. Wang and
D. Stahl,
"Highly multiplexed immune repertoire sequencing links multiple lymphocyte classes with severity of response to COVID-19",
EClinicalMedicine,
vol. 48,
pp. 101438,
2022.
| DOI: | 10.1016/j.eclinm.2022.101438 |
R. Dannebaum,
P. Suwalski,
H. Asgharian,
Z. G. Du,
J. Weiner,
M. Holtgrewe,
C. Thibeault,
M. Müller,
X. Wang,
J. Saccomanno,
J. Doehn,
R. Hübner,
N. Suttorp,
M. Witzenrath,
S. Hippenstiel,
L. E. Sander,
F. Kurth,
P. Group,
H. Lin,
Z. Karadeniz,
B. Hinzmann,
A. Blüher,
S. Siemann,
D. Telman,
C. Skurk,
W. Poller,
D. Beule,
T. Guettouche,
U. Landmesser,
J. Berka,
K. Luong,
F. Rubelt and
B. Heidecker,
"Highly multiplexed immune repertoire sequencing links multiple lymphocyte classes with severity of response to COVID-19.",
EClinicalMedicine.2022;48:101438,
2022.
K. Hönzke,
B. Obermayer,
C. Mache,
D. Fathykova,
M. Kessler,
S. Dökel,
E. Wyler,
M. Baumgardt,
A. Löwa,
K. Hoffmann and
D. Stahl,
"Human lungs show limited permissiveness for SARS-CoV-2 due to scarce ACE2 levels but virus-induced expansion of inflammatory macrophages",
Eur Respir J,
vol. 60,
no. 6,
pp. 2102725,
2022.
| DOI: | 10.1183/13993003.02725-2021 |
K. Hönzke,
B. Obermayer,
C. Mache,
D. Fathykova,
M. Kessler and
e. a. Dökel,
"Human lungs show limited permissiveness for SARS-CoV-2 due to scarce ACE2 levels but virus-induced expansion of inflammatory macrophages",
Eur Respir J,
vol. 60,
no. 6,
pp. 2102725,
2022.
| DOI: | 10.1183/13993003.02725-2021 |
[en]
A. W. Wolff,
B. Haller,
A. F. Demleitner,
E. Westenberg and
P. Lingor,
"Impact of the COVID-19 pandemic on patients with Parkinson's
Disease from the perspective of treating physicians-A nationwide
cross-sectional study",
Brain Sci.,
vol. 12,
no. 3,
pp. 353,
Mä.
2022.
MDPI AG.
Abstract:
The COVID-19 pandemic has posed challenges to maintaining medical care for patients with Parkinson's disease (PD). The Parkinson's Disease during the COVID-19 Pandemic (ParCoPa) survey was conducted as an online, nationwide, cross-sectional survey from December 2020 to March 2021 and aimed to assess the impact of the pandemic on the medical care of PD patients from the physicians' perspective. Invitations containing a randomly generated registration code were mailed to healthcare professionals from sixty-seven specialty centers in Germany. Confounders for the worsening of subjective treatment quality, perceived health risk due to the profession, and adequate protective measures against SARS-CoV-2 were assessed using logistic regression analysis. Of all forty physicians who responded, 87.5% reported a worsening of motor and nonmotor symptoms in their patients, 97.5% experienced cancellation of appointments, and difficulties in organizing advanced and supplementary therapies were reported by over 95%. Participants offered alternative consultation options, mostly in the form of telephone (77.5%) or online (64.1%) consultations, but telephone consultations were the most accepted by patients ("broadly accepted", 40.0%). We identified pandemic-related deficits in providing care for patients with PD and areas of improvement to ensure continued care for this vulnerable patient population.
Abstract:
The COVID-19 pandemic has posed challenges to maintaining medical care for patients with Parkinson's disease (PD). The Parkinson's Disease during the COVID-19 Pandemic (ParCoPa) survey was conducted as an online, nationwide, cross-sectional survey from December 2020 to March 2021 and aimed to assess the impact of the pandemic on the medical care of PD patients from the physicians' perspective. Invitations containing a randomly generated registration code were mailed to healthcare professionals from sixty-seven specialty centers in Germany. Confounders for the worsening of subjective treatment quality, perceived health risk due to the profession, and adequate protective measures against SARS-CoV-2 were assessed using logistic regression analysis. Of all forty physicians who responded, 87.5% reported a worsening of motor and nonmotor symptoms in their patients, 97.5% experienced cancellation of appointments, and difficulties in organizing advanced and supplementary therapies were reported by over 95%. Participants offered alternative consultation options, mostly in the form of telephone (77.5%) or online (64.1%) consultations, but telephone consultations were the most accepted by patients ("broadly accepted", 40.0%). We identified pandemic-related deficits in providing care for patients with PD and areas of improvement to ensure continued care for this vulnerable patient population.
B. Sedlmayr,
M. Sedlmayr,
C. Schüttler and
et al,
"Improving collaborative COVID-19 research of University Hospitals in Germany: Formative usability evaluation of the CODEX-Feasibility Portal",
Appl Clin Inform,
vol. 13,
pp. 400—409,
2022.
| DOI: | 10.1055/s-0042-1744549 |
P. R. Wratil,
N. A. Schmacke,
A. Osterman and
et al,
"In-depth profiling of COVID-19 risk factors and preventive measures in healthcare workers",
Infection,
vol. 50,
2022.
| DOI: | 10.1007/s15010-021-01672-z |
N. Dragano,
M. Reuter,
A. Peters,
M. Engels,
B. Schmidt,
K. Greiser,
B. Bohn,
S. Riedel-Heller,
A. Karch,
R. Mikolajczyk,
G. Krause,
O. Lang,
L. Panreck,
M. Rietschel,
H. Brenner,
B. Fischer,
C. Franzke,
S. Gastell,
B. Holleczek,
K. Jöckel,
R. Kaaks,
T. Keil,
A. Kluttig,
O. Kuß,
N. Legath,
M. Leitzmann,
W. Lieb,
C. Meinke-Franze,
K. Michels,
N. Obi,
T. Pischon,
I. Feinkohl,
S. Rospleszcz,
T. Schikowski,
M. Schulze,
A. Stang,
H. Völzke,
S. Willlich,
K. Wirkner,
H. Zeeb and
K. Berger,
"Increase in mental disorders during the COVID-19 pandemic - the role of occupational and financial strains. An analysis of the German National Cohort (NAKO) Study",
Deutsches Ärzteblatt International,
vol. 119,
pp. 179–187,
2022.
| DOI: | 10.3238/arztebl.m2022.0133 |
A. Bludau,
S. Heinemann,
A. A. Mardiko,
H. E. J. Kaba,
A. Leha,
N. Maltzahn,
N. T. Mutters,
R. Leistner,
F. Mattner and
S. Scheithauer,
"Infection control strategies for patients and accompanying persons during the COVID-19 pandemic in German hospitals: a cross-sectional study in March-April 2021",
The Journal of hospital infection,
vol. 125,
pp. 28—36,
2022.
Abstract:
BACKGROUND Patients are at risk of nosocomial COVID-19 infection. The role of accompanying persons/visitors as potential infection donors is not yet well researched, but the risk will be influenced by prevention measures recommended by infection control practitioners. AIM To collect information about COVID-19 infection control strategies for patients and accompanying persons from infection control practitioners in German hospitals. METHODS A cross-sectional questionnaire was developed, ethically approved, pre-tested and formatted as an online tool. Infection control practitioners in 987 randomly selected German hospitals were invited to participate in March and April 2021. For statistical analysis, the hospitals were categorized as small (0-499 beds) or large ($\geq$500 beds). FINDINGS One hundred surveys were completed (response rate: 10%). A higher proportion of large (71%) than small (49%) hospitals let patients decide freely whether to wear medical or FFP2 masks. Most hospitals reported spatial separation for COVID-19 patients and non-COVID-19 cases (38%) or additionally for suspected COVID-19 cases (53%). A separation of healthcare teams for these areas existed in 54% of the hospitals. Accompaniment bans were more prevalent in large (52%) than in small hospitals (29%), but large hospitals granted more exemptions. CONCLUSION The decision as to whether to separate areas and teams seemed to depend on the hospital's structural conditions, therefore impairing the implementation of recommendations. Accompaniment regulations differ between hospital sizes and may depend on patient numbers, case type/severity and patients' requirements. In the dynamic situation of a pandemic, it can be difficult to stay up to date with findings and recommendations on infection control.
| DOI: | 10.1016/j.jhin.2022.03.014 |
Abstract:
BACKGROUND Patients are at risk of nosocomial COVID-19 infection. The role of accompanying persons/visitors as potential infection donors is not yet well researched, but the risk will be influenced by prevention measures recommended by infection control practitioners. AIM To collect information about COVID-19 infection control strategies for patients and accompanying persons from infection control practitioners in German hospitals. METHODS A cross-sectional questionnaire was developed, ethically approved, pre-tested and formatted as an online tool. Infection control practitioners in 987 randomly selected German hospitals were invited to participate in March and April 2021. For statistical analysis, the hospitals were categorized as small (0-499 beds) or large ($\geq$500 beds). FINDINGS One hundred surveys were completed (response rate: 10%). A higher proportion of large (71%) than small (49%) hospitals let patients decide freely whether to wear medical or FFP2 masks. Most hospitals reported spatial separation for COVID-19 patients and non-COVID-19 cases (38%) or additionally for suspected COVID-19 cases (53%). A separation of healthcare teams for these areas existed in 54% of the hospitals. Accompaniment bans were more prevalent in large (52%) than in small hospitals (29%), but large hospitals granted more exemptions. CONCLUSION The decision as to whether to separate areas and teams seemed to depend on the hospital's structural conditions, therefore impairing the implementation of recommendations. Accompaniment regulations differ between hospital sizes and may depend on patient numbers, case type/severity and patients' requirements. In the dynamic situation of a pandemic, it can be difficult to stay up to date with findings and recommendations on infection control.
T. Houwaart,
S. Belhaj,
E. Tawalbeh,
D. Nagels,
Y. Fröhlich,
P. Finzer,
P. Ciruela,
A. Sabrià,
M. Herrero,
C. Andrés,
A. Antón,
A. Benmoumene,
D. Asskali,
H. Haidar,
J. Dahlen,
J. Nicolai,
M. Stiller,
J. Blum,
C. Lange,
B. Schroer,
U. Osmers,
C. Grice,
P. P. Kirfel,
H. Jomaa,
D. Strelow,
L. Hülse,
M. Pigulla,
P. Kreuzer,
A. Tyshaieva,
J. Weber,
T. Wienemann,
M. Kohns Vasconcelos,
K. Hoffmann,
N. Lübke,
S. Hauka,
C. J. Scholz,
N. Jazmati,
K. Göbels,
R. Zotz,
K. Pfeffer,
J. Timm,
L. Ehlkes,
A. Walker and
A. T. Dilthey,
"Integrated genomic surveillance enables tracing of person-to-person SARS-CoV-2 transmission chains during community transmission and reveals extensive onward transmission of travel-imported infections, Germany, June to July 2021",
Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,
vol. 27,
no. 43,
2022.
Abstract:
BackgroundTracking person-to-person SARS-CoV-2 transmission in the population is important to understand the epidemiology of community transmission and may contribute to the containment of SARS-CoV-2. Neither contact tracing nor genomic surveillance alone, however, are typically sufficient to achieve this objective.AimWe demonstrate the successful application of the integrated genomic surveillance (IGS) system of the German city of Düsseldorf for tracing SARS-CoV-2 transmission chains in the population as well as detecting and investigating travel-associated SARS-CoV-2 infection clusters.MethodsGenomic surveillance, phylogenetic analysis, and structured case interviews were integrated to elucidate two genetically defined clusters of SARS-CoV-2 isolates detected by IGS in Düsseldorf in July 2021.ResultsCluster 1 (n = 67 Düsseldorf cases) and Cluster 2 (n = 36) were detected in a surveillance dataset of 518 high-quality SARS-CoV-2 genomes from Düsseldorf (53% of total cases, sampled mid-June to July 2021). Cluster 1 could be traced back to a complex pattern of transmission in nightlife venues following a putative importation by a SARS-CoV-2-infected return traveller (IP) in late June; 28 SARS-CoV-2 cases could be epidemiologically directly linked to IP. Supported by viral genome data from Spain, Cluster 2 was shown to represent multiple independent introduction events of a viral strain circulating in Catalonia and other European countries, followed by diffuse community transmission in Düsseldorf.ConclusionIGS enabled high-resolution tracing of SARS-CoV-2 transmission in an internationally connected city during community transmission and provided infection chain-level evidence of the downstream propagation of travel-imported SARS-CoV-2 cases.
| DOI: | 10.2807/1560-7917.ES.2022.27.43.2101089 |
Abstract:
BackgroundTracking person-to-person SARS-CoV-2 transmission in the population is important to understand the epidemiology of community transmission and may contribute to the containment of SARS-CoV-2. Neither contact tracing nor genomic surveillance alone, however, are typically sufficient to achieve this objective.AimWe demonstrate the successful application of the integrated genomic surveillance (IGS) system of the German city of Düsseldorf for tracing SARS-CoV-2 transmission chains in the population as well as detecting and investigating travel-associated SARS-CoV-2 infection clusters.MethodsGenomic surveillance, phylogenetic analysis, and structured case interviews were integrated to elucidate two genetically defined clusters of SARS-CoV-2 isolates detected by IGS in Düsseldorf in July 2021.ResultsCluster 1 (n = 67 Düsseldorf cases) and Cluster 2 (n = 36) were detected in a surveillance dataset of 518 high-quality SARS-CoV-2 genomes from Düsseldorf (53% of total cases, sampled mid-June to July 2021). Cluster 1 could be traced back to a complex pattern of transmission in nightlife venues following a putative importation by a SARS-CoV-2-infected return traveller (IP) in late June; 28 SARS-CoV-2 cases could be epidemiologically directly linked to IP. Supported by viral genome data from Spain, Cluster 2 was shown to represent multiple independent introduction events of a viral strain circulating in Catalonia and other European countries, followed by diffuse community transmission in Düsseldorf.ConclusionIGS enabled high-resolution tracing of SARS-CoV-2 transmission in an internationally connected city during community transmission and provided infection chain-level evidence of the downstream propagation of travel-imported SARS-CoV-2 cases.
A. Müller,
H. Haneke,
V. Kirchberger,
G. Mastella,
M. Dommasch,
U. Merle,
O. Heinze,
A. Siegmann,
C. Spinner,
A. Buiatti,
K. Laugwitz,
G. Schmidt and
E. Martens,
"Integration of mobile sensors in a telemedicine hospital system: Remote-monitoring in COVID-19 patients",
Journal of Public Health,
vol. 30,
no. 1,
pp. 93—97,
2022.
| DOI: | 10.1007/s10389-021-01655-2 |
M. Kantauskaite and
et al,
"Intensity of mycophenolate mofetil treatment is associated with an impaired immune response to SARS-CoV-2 vaccination in kidney transplant recipients",
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons,
vol. 22,
pp. 634–639,
2022.
| DOI: | 10.1111/ajt.16851 |
Oorschot and
D. Stahl,
"Interaktive Homepage für Trauernde in Pandemiezeiten",
Schmerz, Nervenarzt, Forum DKG, Urologe, Onkologe,
2022.
P. Dönges,
J. Wagner,
S. Contreras,
E. N. Iftekhar,
S. Bauer,
S. B. Mohr,
J. Dehning,
A. C. Valdez,
M. Kretzschmar,
M. Mäs,
K. Nagel and
V. Priesemann,
"Interplay Between Risk Perception, Behavior, and COVID-19 Spread",
Frontiers in Physics,
vol. 10,
pp. 842180,
2022.
| DOI: | 10.3389/fphy.2022.842180 |
[eng]
S. Stillfried,
R. D. Bülow,
R. Röhrig,
P. Meybohm,
P. Boor and
D. C. COVID-19 Autopsies (DeRegCOVID),
"Intracranial hemorrhage in COVID-19 patients during extracorporeal membrane oxygenation for acute respiratory failure: a nationwide register study report",
Critical Care (London, England),
vol. 26,
no. 1,
pp. 83,
Mä.
2022.
Abstract:
BACKGROUND: In severe cases, SARS-CoV-2 infection leads to acute respiratory distress syndrome (ARDS), often treated by extracorporeal membrane oxygenation (ECMO). During ECMO therapy, anticoagulation is crucial to prevent device-associated thrombosis and device failure, however, it is associated with bleeding complications. In COVID-19, additional pathologies, such as endotheliitis, may further increase the risk of bleeding complications. To assess the frequency of bleeding events, we analyzed data from the German COVID-19 autopsy registry (DeRegCOVID). METHODS: The electronic registry uses a web-based electronic case report form. In November 2021, the registry included N = 1129 confirmed COVID-19 autopsy cases, with data on 63 ECMO autopsy cases and 1066 non-ECMO autopsy cases, contributed from 29 German sites. FINDINGS: The registry data showed that ECMO was used in younger male patients and bleeding events occurred much more frequently in ECMO cases compared to non-ECMO cases (56% and 9%, respectively). Similarly, intracranial bleeding (ICB) was documented in 21% of ECMO cases and 3% of non-ECMO cases and was classified as the immediate or underlying cause of death in 78% of ECMO cases and 37% of non-ECMO cases. In ECMO cases, the three most common immediate causes of death were multi-organ failure, ARDS and ICB, and in non-ECMO cases ARDS, multi-organ failure and pulmonary bacterial ± fungal superinfection, ordered by descending frequency. INTERPRETATION: Our study suggests the potential value of autopsies and a joint interdisciplinary multicenter (national) approach in addressing fatal complications in COVID-19.
| DOI: | 10.1186/s13054-022-03945-x |
Abstract:
BACKGROUND: In severe cases, SARS-CoV-2 infection leads to acute respiratory distress syndrome (ARDS), often treated by extracorporeal membrane oxygenation (ECMO). During ECMO therapy, anticoagulation is crucial to prevent device-associated thrombosis and device failure, however, it is associated with bleeding complications. In COVID-19, additional pathologies, such as endotheliitis, may further increase the risk of bleeding complications. To assess the frequency of bleeding events, we analyzed data from the German COVID-19 autopsy registry (DeRegCOVID). METHODS: The electronic registry uses a web-based electronic case report form. In November 2021, the registry included N = 1129 confirmed COVID-19 autopsy cases, with data on 63 ECMO autopsy cases and 1066 non-ECMO autopsy cases, contributed from 29 German sites. FINDINGS: The registry data showed that ECMO was used in younger male patients and bleeding events occurred much more frequently in ECMO cases compared to non-ECMO cases (56% and 9%, respectively). Similarly, intracranial bleeding (ICB) was documented in 21% of ECMO cases and 3% of non-ECMO cases and was classified as the immediate or underlying cause of death in 78% of ECMO cases and 37% of non-ECMO cases. In ECMO cases, the three most common immediate causes of death were multi-organ failure, ARDS and ICB, and in non-ECMO cases ARDS, multi-organ failure and pulmonary bacterial ± fungal superinfection, ordered by descending frequency. INTERPRETATION: Our study suggests the potential value of autopsies and a joint interdisciplinary multicenter (national) approach in addressing fatal complications in COVID-19.
S. Stillfried,
R. Bülow,
R. Röhrig,
P. Meybohm and
P. Boor,
"Intracranial hemorrhage in COVID-19 patients during extracorporeal membrane oxygenation for acute respiratory failure: a nationwide register study report",
Critical care (London, England),
vol. 26,
pp. 83,
2022.
| DOI: | 10.1186/s13054-022-03945-x |
B. Pauli,
J. Strupp,
K. Schloesser and
D. Stahl,
"It’s like standing in front of a prison fence – Dying during the SARS-CoV2 pandemic: A qualitative study of bereaved relatives’ experiences",
Palliative Medicine,
2022.
| DOI: | 10.1177/02692163221076355 |
[en]
E. Wyler,
K. Eschke,
G. Teixeira Alves,
S. Peidli,
F. Pott,
J. Kazmierski,
L. Michalick,
O. Kershaw,
J. Bushe,
P. Pennitz,
D. Postmus,
C. Goffinet,
J. Kreye,
S. M. Reincke,
H. Prüss,
N. Blüthgen,
A. D. Gruber,
W. M. Kuebler,
M. Witzenrath,
M. Landthaler,
G. Nouailles and
J. Trimpert,
"Key benefits of dexamethasone and antibody treatment in COVID-19 hamster models revealed by single-cell transcriptomics",
Mol. Ther.,
vol. 30,
no. 5,
pp. 1952—1965,
Mai
2022.
Elsevier BV.
Abstract:
For coronavirus disease 2019 (COVID-19), effective and well-understood treatment options are still scarce. Since vaccine efficacy is challenged by novel variants, short-lasting immunity, and vaccine hesitancy, understanding and optimizing therapeutic options remains essential. We aimed at better understanding the effects of two standard-of-care drugs, dexamethasone and anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies, on infection and host responses. By using two COVID-19 hamster models, pulmonary immune responses were analyzed to characterize effects of single or combinatorial treatments. Pulmonary viral burden was reduced by anti-SARS-CoV-2 antibody treatment and unaltered or increased by dexamethasone alone. Dexamethasone exhibited strong anti-inflammatory effects and prevented fulminant disease in a severe disease model. Combination therapy showed additive benefits with both anti-viral and anti-inflammatory potency. Bulk and single-cell transcriptomic analyses confirmed dampened inflammatory cell recruitment into lungs upon dexamethasone treatment and identified a specifically responsive subpopulation of neutrophils, thereby indicating a potential mechanism of action. Our analyses confirm the anti-inflammatory properties of dexamethasone and suggest possible mechanisms, validate anti-viral effects of anti-SARS-CoV-2 antibody treatment, and reveal synergistic effects of a combination therapy, thus informing more effective COVID-19 therapies.
| DOI: | 10.1016/j.ymthe.2022.03.014 |
| Pubmed: | 35339689 |
Abstract:
For coronavirus disease 2019 (COVID-19), effective and well-understood treatment options are still scarce. Since vaccine efficacy is challenged by novel variants, short-lasting immunity, and vaccine hesitancy, understanding and optimizing therapeutic options remains essential. We aimed at better understanding the effects of two standard-of-care drugs, dexamethasone and anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies, on infection and host responses. By using two COVID-19 hamster models, pulmonary immune responses were analyzed to characterize effects of single or combinatorial treatments. Pulmonary viral burden was reduced by anti-SARS-CoV-2 antibody treatment and unaltered or increased by dexamethasone alone. Dexamethasone exhibited strong anti-inflammatory effects and prevented fulminant disease in a severe disease model. Combination therapy showed additive benefits with both anti-viral and anti-inflammatory potency. Bulk and single-cell transcriptomic analyses confirmed dampened inflammatory cell recruitment into lungs upon dexamethasone treatment and identified a specifically responsive subpopulation of neutrophils, thereby indicating a potential mechanism of action. Our analyses confirm the anti-inflammatory properties of dexamethasone and suggest possible mechanisms, validate anti-viral effects of anti-SARS-CoV-2 antibody treatment, and reveal synergistic effects of a combination therapy, thus informing more effective COVID-19 therapies.
F. P,
K. J,
P. T,
L. S,
M. V,
F. S,
S. H,
D. C,
S. M,
Z. S,
S. M,
M. D,
F. GR and
A. N,
"Meaningful use of imaging resources to rule out cerebral venous sinus thrombosis after ChAdOx1 COVID-19 vaccination: Evaluation of the AHA diagnostic algorithm with a clinical cohort and a systematic data review.",
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia,
Aug.
2022.
Abstract:
Vaccin-induzierte immunthrombotische Thrombozytopenie (VITT) mit cerebraler venöser Thrombose (CVST) ist eine unwahrscheinliche (0.0005%), aber möglicherweise tödliche Komplikation nach ChAdOx1 Impfung. Andererseits gehört Kopfschmerzen zu den häufigsten Nebenwirkungen von ChAdOx1 (29,3%). Im September 2021 schlug die American Heart Association (AHA) einen diagnostischen Workflow vor, um die risikoadaptierte Verwendung von bildgebenden Ressourcen für Patienten mit neurologischen Symptomen nach ChAdOx1 zu erleichtern. Wir wollten den AHA-Workflow in einem retrospektiven Patientenkohort bewerten, der nach ChAdOx1 an vier primären Pflegekrankenhäusern in Deutschland präsentiert. Wissenschaftliche Literatur wurde für Fallberichte von VITT mit CVST nach ChAdOx1, veröffentlicht bis 1. September 2021. Einhundertdreizehn aufeinanderfolgende Patienten (77 weiblich, mittleres Alter 38,7 +/- 11,9 Jahre) wurden an unseren Instituten bewertet, darunter ein Fall von VITT mit CVST. Weitere 228 Fallberichte von VITT mit CVST werden in jüngster Literatur veröffentlicht, die Thrombozyten-Thema (225/227 berichtet) und erhöhte d-Dimer-Spiegel (100/101 berichtet) teilen. Der AHA-Workflow hätte alle VITT-Fälle mit CVST (100% Empfindlichkeit) erkannt, die für die Diagnose (NND) benötigte Anzahl betrug 1:113. Die anfängliche Auswertung von Thrombocytopenie oder erhöhten d-Dimer-Spiegeln hätte den NND auf 1:68 reduziert, ohne dass die Empfindlichkeit gekostet wäre. Daher schlagen wir vor, dass bei normalen Thrombozyten- und d-Dimerenspiegeln der Zugang zu weiteren Diagnostiken durch die etablierten klinischen Überlegungen unabhängig von der Impfungsgeschichte begrenzt werden sollte.
| DOI: | 10.1016/j.jocn.2022.05.031 |
Abstract:
Vaccin-induzierte immunthrombotische Thrombozytopenie (VITT) mit cerebraler venöser Thrombose (CVST) ist eine unwahrscheinliche (0.0005%), aber möglicherweise tödliche Komplikation nach ChAdOx1 Impfung. Andererseits gehört Kopfschmerzen zu den häufigsten Nebenwirkungen von ChAdOx1 (29,3%). Im September 2021 schlug die American Heart Association (AHA) einen diagnostischen Workflow vor, um die risikoadaptierte Verwendung von bildgebenden Ressourcen für Patienten mit neurologischen Symptomen nach ChAdOx1 zu erleichtern. Wir wollten den AHA-Workflow in einem retrospektiven Patientenkohort bewerten, der nach ChAdOx1 an vier primären Pflegekrankenhäusern in Deutschland präsentiert. Wissenschaftliche Literatur wurde für Fallberichte von VITT mit CVST nach ChAdOx1, veröffentlicht bis 1. September 2021. Einhundertdreizehn aufeinanderfolgende Patienten (77 weiblich, mittleres Alter 38,7 +/- 11,9 Jahre) wurden an unseren Instituten bewertet, darunter ein Fall von VITT mit CVST. Weitere 228 Fallberichte von VITT mit CVST werden in jüngster Literatur veröffentlicht, die Thrombozyten-Thema (225/227 berichtet) und erhöhte d-Dimer-Spiegel (100/101 berichtet) teilen. Der AHA-Workflow hätte alle VITT-Fälle mit CVST (100% Empfindlichkeit) erkannt, die für die Diagnose (NND) benötigte Anzahl betrug 1:113. Die anfängliche Auswertung von Thrombocytopenie oder erhöhten d-Dimer-Spiegeln hätte den NND auf 1:68 reduziert, ohne dass die Empfindlichkeit gekostet wäre. Daher schlagen wir vor, dass bei normalen Thrombozyten- und d-Dimerenspiegeln der Zugang zu weiteren Diagnostiken durch die etablierten klinischen Überlegungen unabhängig von der Impfungsgeschichte begrenzt werden sollte.
S. Krishnaratne,
H. Littlecott,
K. Sell,
J. Burns,
J. E. Rabe,
J. M. Stratil,
T. Litwin,
C. Kreutz,
M. Coenen,
K. Geffert,
A. H. Boger,
A. Movsisyan,
S. Kratzer,
C. Klinger,
K. Wabnitz,
B. Strahwald,
B. Verboom,
E. Rehfuess,
R. L. Biallas,
C. Jung-Sievers,
S. Voss and
L. M. Pfadenhauer,
"Measures implemented in the school setting to contain the COVID-19 pandemic: a rapid review",
Cochrane Database of Systematic Reviews,
vol. 2022,
pp. CD015029,
2022.
| DOI: | 10.1002/14651858.CD015029 |
D. Jonigk,
"Microvascular placental alterations in maternal COVID-19",
American Journal of Obstetrics & Gynecology,
vol. 226,
pp. 135-136,
Jan.
2022.
| DOI: | https://doi.org/10.1016/j.ajog.2021.06.098 |
J. Schwartz,
M. C. Reuters,
M. Schallenburger,
S. Meier,
C. Roch,
L. Werner,
B. Oorschot and
M. Neukirchen,
"Modelle guter Praxis: Alleine sterben ist ethisch nicht vertretbar",
Praxis Palliative Care,
vol. 54,
pp. 29-36,
2022.
N. Wanner,
G. Andrieux,
P. Badia-i-Mompel and
et al,
"Molecular consequences of SARS-CoV-2 liver tropism",
Nat Metab,
vol. 4,
pp. 310-319,
2022.
| DOI: | 10.1038/s42255-022-00552-6 |
H. Gruell and
et al,
"mRNA booster immunization elicits potent neutralizing serum activity against the SARS-CoV-2 Omicron variant",
Nature Medicine,
2022.
| DOI: | 10.1038/s41591-021-01676-0 |
Z. Liu and
et al,
"Multi-Omics Integration Reveals Only Minor Long-Term Molecular and Functional Sequelae in Immune Cells of Individuals Recovered From COVID-19",
Frontiers in immunology,
vol. 13,
pp. 838132,
2022.
| DOI: | 10.3389/fimmu.2022.838132 |
T. Illig,
"NAPKON- Eine Erfolgsgeschichte",
Plenarvortrag, Nationales Biobanken Symposium,
2022.
C. Bausewein,
F. Hodiamont,
N. Berges,
A. Ullrich,
C. Gerlach,
K. Oechsle,
B. Pauli,
J. Weber,
S. Stiel,
N. Schneider and
D. Stahl,
"National strategy for palliative care of severely ill and dying people and their relatives in pandemics (PallPan) in Germany - study protocol of a mixed-methods project",
BMC palliative care,
vol. 21,
no. 1,
pp. 10,
2022.
| DOI: | 10.1186/s12904-021-00898-w |
[eng]
F. Heinrich,
K. Roedl,
D. Jarczak,
H. Goebels,
A. Heinemann,
U. Schäfer,
F. Ludwig,
M. Bachmann,
B. Bein,
C. F. Weber,
K. Sydow,
M. Bota,
H. Paschen,
A. Weerth,
C. Veit,
O. Detsch,
P. Brand,
S. Kluge,
B. Ondruschka and
D. Wichmann,
"New Insights in the Occurrence of Venous Thromboembolism in Critically Ill Patients with COVID-19-A Large Postmortem and Clinical Analysis",
Viruses,
vol. 14,
no. 4,
pp. 811,
Apr.
2022.
Abstract:
Critically ill COVID-19 patients are at high risk for venous thromboembolism (VTE), namely deep vein thrombosis (DVT) and/or pulmonary embolism (PE), and death. The optimal anticoagulation strategy in critically ill patients with COVID-19 remains unknown. This study investigated the ante mortem incidence as well as postmortem prevalence of VTE, the factors predictive of VTE, and the impact of changed anticoagulation practice on patient survival. We conducted a consecutive retrospective analysis of postmortem COVID-19 (n = 64) and non-COVID-19 (n = 67) patients, as well as ante mortem COVID-19 (n = 170) patients admitted to the University Medical Center Hamburg-Eppendorf (Hamburg, Germany). Baseline patient characteristics, parameters related to the intensive care unit (ICU) stay, and the clinical and autoptic presence of VTE were evaluated and statistically compared between groups. The occurrence of VTE in critically ill COVID-19 patients is confirmed in both ante mortem (17%) and postmortem (38%) cohorts. Accordingly, comparing the postmortem prevalence of VTE between age- and sex-matched COVID-19 (43%) and non-COVID-19 (0%) cohorts, we found the statistically significant increased prevalence of VTE in critically ill COVID-19 cohorts (p = 0.001). A change in anticoagulation practice was associated with the statistically significant prolongation of survival time (HR: 2.55, [95% CI 1.41-4.61], p = 0.01) and a reduction in VTE occurrence (54% vs. 25%; p = 0.02). In summary, in the autopsy as well as clinical cohort of critically ill patients with COVID-19, we found that VTE was a frequent finding. A change in anticoagulation practice was associated with a statistically significantly prolonged survival time.
| DOI: | 10.3390/v14040811 |
Abstract:
Critically ill COVID-19 patients are at high risk for venous thromboembolism (VTE), namely deep vein thrombosis (DVT) and/or pulmonary embolism (PE), and death. The optimal anticoagulation strategy in critically ill patients with COVID-19 remains unknown. This study investigated the ante mortem incidence as well as postmortem prevalence of VTE, the factors predictive of VTE, and the impact of changed anticoagulation practice on patient survival. We conducted a consecutive retrospective analysis of postmortem COVID-19 (n = 64) and non-COVID-19 (n = 67) patients, as well as ante mortem COVID-19 (n = 170) patients admitted to the University Medical Center Hamburg-Eppendorf (Hamburg, Germany). Baseline patient characteristics, parameters related to the intensive care unit (ICU) stay, and the clinical and autoptic presence of VTE were evaluated and statistically compared between groups. The occurrence of VTE in critically ill COVID-19 patients is confirmed in both ante mortem (17%) and postmortem (38%) cohorts. Accordingly, comparing the postmortem prevalence of VTE between age- and sex-matched COVID-19 (43%) and non-COVID-19 (0%) cohorts, we found the statistically significant increased prevalence of VTE in critically ill COVID-19 cohorts (p = 0.001). A change in anticoagulation practice was associated with the statistically significant prolongation of survival time (HR: 2.55, [95% CI 1.41-4.61], p = 0.01) and a reduction in VTE occurrence (54% vs. 25%; p = 0.02). In summary, in the autopsy as well as clinical cohort of critically ill patients with COVID-19, we found that VTE was a frequent finding. A change in anticoagulation practice was associated with a statistically significantly prolonged survival time.
F. Heinrich,
K. Roedl,
D. Jarczak and
et al,
"New Insights in the Occurrence of Venous Thromboembolism in Critically Ill Patients with COVID-19—A Large Postmortem and Clinical Analysis",
Viruses,
vol. 14,
pp. 811,
2022.
| DOI: | 10.3390/v14040811 |
P. Arora and
et al,
"No evidence for increased cell entry or antibody evasion by Delta sublineage AY.4.2",
Cellular & Molecular Immunology,
2022.
| DOI: | 10.1038/s41423-021-00811-8 |
M. S. Ercanoglu and
et al,
"No substantial preexisting B cell immunity against SARS-CoV-2 in healthy adults",
iScience,
vol. 25,
pp. 103951,
2022.
| DOI: | 10.1016/j.isci.2022.103951 |
S. Zellmer,
E. Bachmann,
A. Muzalyova and
et al,
"One year of the COVID-19 pandemic in dental medical facilities in Germany: A questionnaire-based analysis",
Int J Environ Res Public Health,
vol. 19,
no. 1,
2022.
| DOI: | 10.3390/ijerph19010175 |
D. Jonigk,
C. Werlein and
et al,
"Organ manifestations of COVID-19: what have we learned so far (not only) from autopsies?",
Virchows Arch,
2022.
| DOI: | 10.1007/s00428-022-03319-2 |
[eng]
D. Jonigk,
C. Werlein,
G. Baretton,
P. Barth,
R. M. Bohle,
A. Büttner,
R. Büttner,
R. Dettmeyer,
P. Eichhorn,
S. Elezkurtaj,
I. Esposito,
K. Evert,
M. Evert,
F. Fend,
N. Gaßler,
S. Gattenlöhner,
M. Glatzel,
H. Göbel,
E. Gradhand,
T. Hansen,
A. Hartmann,
A. Heinemann,
F. L. Heppner,
J. Hilsenbeck,
D. Horst,
J. C. Kamp,
G. Mall,
B. Märkl,
B. Ondruschka,
J. Pablik,
S. Pfefferle,
A. Quaas,
H. Radbruch,
C. Röcken,
A. Rosenwald,
W. Roth,
M. Rudelius,
P. Schirmacher,
J. Slotta-Huspenina,
K. Smith,
L. Sommer,
K. Stock,
P. Ströbel,
S. Strobl,
U. Titze,
G. Weirich,
J. Weis,
M. Werner,
C. Wickenhauser,
T. Wiech,
P. Wild,
T. Welte,
S. Stillfried and
P. Boor,
"Organ manifestations of COVID-19: what have we learned so far (not only) from autopsies?",
Virchows Archiv: An International Journal of Pathology,
vol. 481,
no. 2,
pp. 139—159,
Aug.
2022.
Abstract:
The use of autopsies in medicine has been declining. The COVID-19 pandemic has documented and rejuvenated the importance of autopsies as a tool of modern medicine. In this review, we discuss the various autopsy techniques, the applicability of modern analytical methods to understand the pathophysiology of COVID-19, the major pathological organ findings, limitations or current studies, and open questions. This article summarizes published literature and the consented experience of the nationwide network of clinical, neuro-, and forensic pathologists from 27 German autopsy centers with more than 1200 COVID-19 autopsies. The autopsy tissues revealed that SARS-CoV-2 can be found in virtually all human organs and tissues, and the majority of cells. Autopsies have revealed the organ and tissue tropism of SARS-CoV-2, and the morphological features of COVID-19. This is characterized by diffuse alveolar damage, combined with angiocentric disease, which in turn is characterized by endothelial dysfunction, vascular inflammation, (micro-) thrombosis, vasoconstriction, and intussusceptive angiogenesis. These findings explained the increased pulmonary resistance in COVID-19 and supported the recommendations for antithrombotic treatment in COVID-19. In contrast, in extra-respiratory organs, pathological changes are often nonspecific and unclear to which extent these changes are due to direct infection vs. indirect/secondary mechanisms of organ injury, or a combination thereof. Ongoing research using autopsies aims at answering questions on disease mechanisms, e.g., focusing on variants of concern, and future challenges, such as post-COVID conditions. Autopsies are an invaluable tool in medicine and national and international interdisciplinary collaborative autopsy-based research initiatives are essential.
| DOI: | 10.1007/s00428-022-03319-2 |
Abstract:
The use of autopsies in medicine has been declining. The COVID-19 pandemic has documented and rejuvenated the importance of autopsies as a tool of modern medicine. In this review, we discuss the various autopsy techniques, the applicability of modern analytical methods to understand the pathophysiology of COVID-19, the major pathological organ findings, limitations or current studies, and open questions. This article summarizes published literature and the consented experience of the nationwide network of clinical, neuro-, and forensic pathologists from 27 German autopsy centers with more than 1200 COVID-19 autopsies. The autopsy tissues revealed that SARS-CoV-2 can be found in virtually all human organs and tissues, and the majority of cells. Autopsies have revealed the organ and tissue tropism of SARS-CoV-2, and the morphological features of COVID-19. This is characterized by diffuse alveolar damage, combined with angiocentric disease, which in turn is characterized by endothelial dysfunction, vascular inflammation, (micro-) thrombosis, vasoconstriction, and intussusceptive angiogenesis. These findings explained the increased pulmonary resistance in COVID-19 and supported the recommendations for antithrombotic treatment in COVID-19. In contrast, in extra-respiratory organs, pathological changes are often nonspecific and unclear to which extent these changes are due to direct infection vs. indirect/secondary mechanisms of organ injury, or a combination thereof. Ongoing research using autopsies aims at answering questions on disease mechanisms, e.g., focusing on variants of concern, and future challenges, such as post-COVID conditions. Autopsies are an invaluable tool in medicine and national and international interdisciplinary collaborative autopsy-based research initiatives are essential.
Oorschot and
D. Stahl,
"PallPan Richtig handeln in der Betreuung Schwerkranker und Sterbender in Pandemiezeiten",
Der Ophthalmologe,
2022.
J. Ebler,
P. Ebert,
W. E. Clarke,
T. Rausch,
P. A. Audano,
T. Houwaart,
Y. Mao,
J. O. Korbel,
E. E. Eichler,
M. C. Zody,
A. T. Dilthey and
T. Marschall,
"Pangenome-based genome inference allows efficient and accurate genotyping across a wide spectrum of variant classes",
Nature genetics,
vol. 54,
no. 4,
pp. 518—525,
2022.
Abstract:
Typical genotyping workflows map reads to a reference genome before identifying genetic variants. Generating such alignments introduces reference biases and comes with substantial computational burden. Furthermore, short-read lengths limit the ability to characterize repetitive genomic regions, which are particularly challenging for fast k-mer-based genotypers. In the present study, we propose a new algorithm, PanGenie, that leverages a haplotype-resolved pangenome reference together with k-mer counts from short-read sequencing data to genotype a wide spectrum of genetic variation-a process we refer to as genome inference. Compared with mapping-based approaches, PanGenie is more than 4 times faster at 30-fold coverage and achieves better genotype concordances for almost all variant types and coverages tested. Improvements are especially pronounced for large insertions ($\geq$50 bp) and variants in repetitive regions, enabling the inclusion of these classes of variants in genome-wide association studies. PanGenie efficiently leverages the increasing amount of haplotype-resolved assemblies to unravel the functional impact of previously inaccessible variants while being faster compared with alignment-based workflows.
| DOI: | 10.1038/s41588-022-01043-w |
Abstract:
Typical genotyping workflows map reads to a reference genome before identifying genetic variants. Generating such alignments introduces reference biases and comes with substantial computational burden. Furthermore, short-read lengths limit the ability to characterize repetitive genomic regions, which are particularly challenging for fast k-mer-based genotypers. In the present study, we propose a new algorithm, PanGenie, that leverages a haplotype-resolved pangenome reference together with k-mer counts from short-read sequencing data to genotype a wide spectrum of genetic variation-a process we refer to as genome inference. Compared with mapping-based approaches, PanGenie is more than 4 times faster at 30-fold coverage and achieves better genotype concordances for almost all variant types and coverages tested. Improvements are especially pronounced for large insertions ($\geq$50 bp) and variants in repetitive regions, enabling the inclusion of these classes of variants in genome-wide association studies. PanGenie efficiently leverages the increasing amount of haplotype-resolved assemblies to unravel the functional impact of previously inaccessible variants while being faster compared with alignment-based workflows.
C. Lemhöfer,
K. S. Appel,
W. Häuser,
N. Hettich,
M. Kohls and
M. C. Polidori,
"Post-COVID: Alles eine Frage der Definition?",
Dtsch Med Wochenschr,
vol. 147,
no. 21,
pp. 1391—1397,
Okt.
2022.
Georg Thieme Verlag KG.
Abstract:
Die Pr"avalenz des Post-COVID-Syndroms (PCS) ist noch nicht abschließend gekl"art. Die bisherigen Definitionen bilden vorrangig zeitliche Aspekte ab, lassen jedoch funktionelle Defizite sowie die Objektivierung von Symptomen außer Acht. Dies f"uhrt zu diagnostischen sowie therapeutischen Unklarheiten. In Pubmed wurde daher nach systematischen Reviews gesucht, die sich mit den Folgen einer SARS-CoV-2-Infektion befassten. Die zugrunde liegenden Definitionen sowie zeitlichen Einschlusskriterien wurden extrahiert. 16 systematische Reviews wurden eingeschlossen, davon 11 mit einer Definition des PCS. In 58 % der analysierten Einzelstudien wurden Patienten mit einer Symptomatik > 12 Wochen und damit entsprechend der Definition des PCS inkludiert. Fazit: Eine weitere Pr"azisierung der Definition des PCS ist notwendig, um Diagnostik und eine multimodale Behandlung zu erleichtern und die knappen therapeutischen Ressourcen entsprechend zu nutzen.
Abstract:
Die Pr"avalenz des Post-COVID-Syndroms (PCS) ist noch nicht abschließend gekl"art. Die bisherigen Definitionen bilden vorrangig zeitliche Aspekte ab, lassen jedoch funktionelle Defizite sowie die Objektivierung von Symptomen außer Acht. Dies f"uhrt zu diagnostischen sowie therapeutischen Unklarheiten. In Pubmed wurde daher nach systematischen Reviews gesucht, die sich mit den Folgen einer SARS-CoV-2-Infektion befassten. Die zugrunde liegenden Definitionen sowie zeitlichen Einschlusskriterien wurden extrahiert. 16 systematische Reviews wurden eingeschlossen, davon 11 mit einer Definition des PCS. In 58 % der analysierten Einzelstudien wurden Patienten mit einer Symptomatik > 12 Wochen und damit entsprechend der Definition des PCS inkludiert. Fazit: Eine weitere Pr"azisierung der Definition des PCS ist notwendig, um Diagnostik und eine multimodale Behandlung zu erleichtern und die knappen therapeutischen Ressourcen entsprechend zu nutzen.
F. Heinrich,
A. Schröder,
A. Gerberding and
et al,
"Postmortem Antigen-Detecting Rapid Diagnostic Tests to Predict Infectivity of SARS-CoV-2-Associated Deaths",
Emerg Infect Dis,
vol. 28,
pp. 244-247,
2022.
| DOI: | 10.3201/eid2801.211749 |
T. Schwarz and
et al,
"Preserved T cell responses to SARS-CoV-2 in anti-CD20 treated multiple sclerosis",
Multiple Sclerosis Journal,
2022.
| DOI: | 10.1101/2021.10.11.21264694 |
H. Gorji,
N. Stauffer,
I. Lunati and
et al,
"Projection of healthcare demand in Germany and Switzerland urged by omicron wave (January-March 2022)",
MedRxiv,
2022.
| DOI: | 10.1101/2022.01.24.22269676 |
C. Dächert,
M. Muenchhoff,
A. Graf and
et al,
"Rapid and sensitive identification of omicron by variant-specific PCR and nanopore sequencing: paradigm for diagnostics of emerging SARS-CoV-2 variants",
Med Microbiol Immunol,
vol. 211,
no. 1,
2022.
| DOI: | 10.1007/s00430-022-00728-7 |
| Datei: | https://doi.org/10.1007/s00430-022-00728-7 |
M. Zickler,
S. Stanelle-Bertram,
S. Ehret and
et al,
"Replication of SARS-CoV-2 in adipose tissue determines organ and systemic lipid metabolism in hamsters and humans",
Cell Metab,
vol. 34,
pp. 1-2,
2022.
| DOI: | 10.1016/j.cmet.2021.12.002 |
M. Neidhardt,
S. Gerlach,
R. Mieling and
et al,
"Robotic Tissue Sampling for Safe Post-Mortem Biopsy in Infectious Corpses",
IEEE Trans. Med. Robot. Bionics,
vol. 4,
pp. 94-105,
2022.
| DOI: | 10.1109/TMRB.2022.3146440 |
S. I. Hammerschmidt,
C. Thurm,
B. Bošnjak and
et al,
"Robust induction of neutralizing antibodies against the SARS‐CoV‐2 Delta variant after homologous Spikevax or heterologous Vaxzevria‐Spikevax vaccination",
Eur J Immunol,
vol. 52,
no. 2,
2022.
| DOI: | 10.1002/eji.202149645 |
S. Momsen Reincke and
et al,
"SARS-CoV-2 Beta variant infection elicits potent lineage-specific and cross-reactive antibodies",
Science (New York, N.Y.),
2022.
| DOI: | 10.1126/science.abm5835 |
[eng]
J. Jansen,
K. C. Reimer,
J. S. Nagai,
F. S. Varghese,
G. J. Overheul,
M. Beer,
R. Roverts,
D. Daviran,
L. A. S. Fermin,
B. Willemsen,
M. Beukenboom,
S. Djudjaj,
S. Stillfried,
L. E. Eijk,
M. Mastik,
M. Bulthuis,
W. d. Dunnen,
H. Goor,
J. Hillebrands,
S. H. Triana,
M. Timm,
B. T. Berge,
M. Broek,
Q. Nlandu,
J. Heijnert,
E. M. J. Bindels,
R. M. Hoogenboezem,
F. Mooren,
C. Kuppe,
P. Miesen,
K. Grünberg,
T. Ijzermans,
E. J. Steenbergen,
J. Czogalla,
M. F. Schreuder,
N. Sommerdijk,
P. Boor,
V. G. Puelles,
J. Floege,
T. B. Huber,
C. M. consortium,
R. P. Rij,
I. G. Costa,
R. K. Schneider,
B. Smeets and
R. Kramann,
"SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids",
Cell Stem Cell,
vol. 29,
no. 2,
pp. 217—231.e8,
Feb.
2022.
Abstract:
Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human-induced pluripotent stem-cell-derived kidney organoids with SARS-CoV-2. Single-cell RNA sequencing indicated injury and dedifferentiation of infected cells with activation of profibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in long COVID.
| DOI: | 10.1016/j.stem.2021.12.010 |
Abstract:
Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human-induced pluripotent stem-cell-derived kidney organoids with SARS-CoV-2. Single-cell RNA sequencing indicated injury and dedifferentiation of infected cells with activation of profibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in long COVID.
E. Layer,
S. Hoehl,
M. Widera,
D. Bojkova,
T. Westphal,
R. Gottschalk,
B. Boeddinghaus,
J. Schork,
S. Ciesek and
U. Goetsch,
"SARS-CoV-2 screening strategies for returning international travellers: Evaluation of a rapid antigen test approach",
International Journal of Infectious Diseases,
vol. 118,
pp. 126—131,
2022.
| DOI: | 10.1016/j.ijid.2022.02.045 |