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  1. Article ; Online: Contamination of personal protective equipment during COVID-19 autopsies.

    Brandner, Johanna M / Boor, Peter / Borcherding, Lukas / Edler, Carolin / Gerber, Sven / Heinemann, Axel / Hilsenbeck, Julia / Kasajima, Atsuko / Lohner, Larissa / Märkl, Bruno / Pablik, Jessica / Schröder, Ann Sophie / Slotta-Huspenina, Julia / Sommer, Linna / Sperhake, Jan-Peter / von Stillfried, Saskia / Dintner, Sebastian

    Virchows Archiv : an international journal of pathology

    2022  Volume 480, Issue 3, Page(s) 519–528

    Abstract: Confronted with an emerging infectious disease at the beginning of the COVID-19 pandemic, the medical community faced concerns regarding the safety of autopsies on those who died of the disease. This attitude has changed, and autopsies are now recognized ...

    Abstract Confronted with an emerging infectious disease at the beginning of the COVID-19 pandemic, the medical community faced concerns regarding the safety of autopsies on those who died of the disease. This attitude has changed, and autopsies are now recognized as indispensable tools for understanding COVID-19, but the true risk of infection to autopsy staff is nevertheless still debated. To clarify the rate of SARS-CoV-2 contamination in personal protective equipment (PPE), swabs were taken at nine points in the PPE of one physician and one assistant after each of 11 full autopsies performed at four centers. Swabs were also obtained from three minimally invasive autopsies (MIAs) conducted at a fifth center. Lung/bronchus swabs of the deceased served as positive controls, and SARS-CoV-2 RNA was detected by real-time RT-PCR. In 9 of 11 full autopsies, PPE samples tested RNA positive through PCR, accounting for 41 of the 198 PPE samples taken (21%). The main contaminated items of the PPE were gloves (64% positive), aprons (50% positive), and the tops of shoes (36% positive) while the fronts of safety goggles, for example, were positive in only 4.5% of the samples, and all the face masks were negative. In MIAs, viral RNA was observed in one sample from a glove but not in other swabs. Infectious virus isolation in cell culture was performed on RNA-positive swabs from the full autopsies. Of all the RNA-positive PPE samples, 21% of the glove samples, taken in 3 of 11 full autopsies, tested positive for infectious virus. In conclusion, PPE was contaminated with viral RNA in 82% of autopsies. In 27% of autopsies, PPE was found to be contaminated even with infectious virus, representing a potential risk of infection to autopsy staff. Adequate PPE and hygiene measures, including appropriate waste deposition, are therefore essential to ensure a safe work environment.
    MeSH term(s) Autopsy ; COVID-19/prevention & control ; Humans ; Pandemics/prevention & control ; Personal Protective Equipment ; RNA, Viral/genetics ; SARS-CoV-2
    Chemical Substances RNA, Viral
    Language English
    Publishing date 2022-01-06
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1184867-4
    ISSN 1432-2307 ; 0945-6317
    ISSN (online) 1432-2307
    ISSN 0945-6317
    DOI 10.1007/s00428-021-03263-7
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  2. Article: Impaired Dendritic Cell Homing in COVID-19.

    Borcherding, Lukas / Teksen, Alime Sema / Grosser, Bianca / Schaller, Tina / Hirschbühl, Klaus / Claus, Rainer / Spring, Oliver / Wittmann, Michael / Römmele, Christoph / Sipos, Éva / Märkl, Bruno

    Frontiers in medicine

    2021  Volume 8, Page(s) 761372

    Abstract: The high mortality of COVID-19 is mostly attributed to acute respiratory distress syndrome (ARDS), whose histopathological correlate is diffuse alveolar damage (DAD). Furthermore, severe COVID-19 is often accompanied by a cytokine storm and a disrupted ... ...

    Abstract The high mortality of COVID-19 is mostly attributed to acute respiratory distress syndrome (ARDS), whose histopathological correlate is diffuse alveolar damage (DAD). Furthermore, severe COVID-19 is often accompanied by a cytokine storm and a disrupted response of the adaptive immune system. Studies aiming to depict this dysregulation have mostly investigated the peripheral cell count as well as the functionality of immune cells. We investigated the impact of SARS-CoV-2 on antigen-presenting cells using multiplexed immunofluorescence. Similar to MERS-CoV and SARS-CoV, SARS-CoV-2 appears to be impairing the maturation of dendritic cells (DCs). DC maturation involves a switch in surface antigen expression, which enables the cells' homing to lymph nodes and the subsequent activation of T-cells. As quantitative descriptions of the local inflammatory infiltrate are still scarce, we compared the cell population of professional antigen-presenting cells (APC) in the lungs of COVID-19 autopsy cases in different stages of DAD. We found an increased count of myeloid dendritic cells (mDCs) in later stages. Interestingly, mDCs also showed no significant upregulation of maturation markers in DAD-specimens with high viral load. Accumulation of immature mDCs, which are unable to home to lymph nodes, ultimately results in an inadequate T-cell response.
    Language English
    Publishing date 2021-11-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2021.761372
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  3. Article ; Online: Impaired Dendritic Cell Homing in COVID-19

    Lukas Borcherding / Alime Sema Teksen / Bianca Grosser / Tina Schaller / Klaus Hirschbühl / Rainer Claus / Oliver Spring / Michael Wittmann / Christoph Römmele / Éva Sipos / Bruno Märkl

    Frontiers in Medicine, Vol

    2021  Volume 8

    Abstract: The high mortality of COVID-19 is mostly attributed to acute respiratory distress syndrome (ARDS), whose histopathological correlate is diffuse alveolar damage (DAD). Furthermore, severe COVID-19 is often accompanied by a cytokine storm and a disrupted ... ...

    Abstract The high mortality of COVID-19 is mostly attributed to acute respiratory distress syndrome (ARDS), whose histopathological correlate is diffuse alveolar damage (DAD). Furthermore, severe COVID-19 is often accompanied by a cytokine storm and a disrupted response of the adaptive immune system. Studies aiming to depict this dysregulation have mostly investigated the peripheral cell count as well as the functionality of immune cells. We investigated the impact of SARS-CoV-2 on antigen-presenting cells using multiplexed immunofluorescence. Similar to MERS-CoV and SARS-CoV, SARS-CoV-2 appears to be impairing the maturation of dendritic cells (DCs). DC maturation involves a switch in surface antigen expression, which enables the cells' homing to lymph nodes and the subsequent activation of T-cells. As quantitative descriptions of the local inflammatory infiltrate are still scarce, we compared the cell population of professional antigen-presenting cells (APC) in the lungs of COVID-19 autopsy cases in different stages of DAD. We found an increased count of myeloid dendritic cells (mDCs) in later stages. Interestingly, mDCs also showed no significant upregulation of maturation markers in DAD-specimens with high viral load. Accumulation of immature mDCs, which are unable to home to lymph nodes, ultimately results in an inadequate T-cell response.
    Keywords dendritic cells ; maturation ; homing ; SARS-CoV-2 ; COVID-19 ; diffuse alveolar damage (DAD) ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2021-11-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Viral mapping in COVID-19 deceased in the Augsburg autopsy series of the first wave: A multiorgan and multimethodological approach.

    Hirschbühl, Klaus / Dintner, Sebastian / Beer, Martin / Wylezich, Claudia / Schlegel, Jürgen / Delbridge, Claire / Borcherding, Lukas / Lippert, Jirina / Schiele, Stefan / Müller, Gernot / Moiraki, Dimitra / Spring, Oliver / Wittmann, Michael / Kling, Elisabeth / Braun, Georg / Kröncke, Thomas / Claus, Rainer / Märkl, Bruno / Schaller, Tina

    PloS one

    2021  Volume 16, Issue 7, Page(s) e0254872

    Abstract: Background: COVID-19 is only partly understood, and the level of evidence available in terms of pathophysiology, epidemiology, therapy, and long-term outcome remains limited. During the early phase of the pandemic, it was necessary to effectively ... ...

    Abstract Background: COVID-19 is only partly understood, and the level of evidence available in terms of pathophysiology, epidemiology, therapy, and long-term outcome remains limited. During the early phase of the pandemic, it was necessary to effectively investigate all aspects of this new disease. Autopsy can be a valuable procedure to investigate the internal organs with special techniques to obtain information on the disease, especially the distribution and type of organ involvement.
    Methods: During the first wave of COVID-19 in Germany, autopsies of 19 deceased patients were performed. Besides gross examination, the organs were analyzed with standard histology and polymerase-chain-reaction for SARS-CoV-2. Polymerase chain reaction positive localizations were further analyzed with immunohistochemistry and RNA-in situ hybridization for SARS-CoV-2.
    Results: Eighteen of 19 patients were found to have died due to COVID-19. Clinically relevant histological changes were only observed in the lungs. Diffuse alveolar damage in considerably different degrees was noted in 18 cases. Other organs, including the central nervous system, did not show specific micromorphological alterations. In terms of SARS-CoV-2 detection, the focus remains on the upper airways and lungs. This is true for both the number of positive samples and the viral load. A highly significant inverse correlation between the stage of diffuse alveolar damage and viral load was found on a case and a sample basis. Mediastinal lymph nodes and fat were also affected by the virus at high frequencies. By contrast, other organs rarely exhibited a viral infection. Moderate to strong correlations between the methods for detecting SARS-CoV-2 were observed for the lungs and for other organs.
    Conclusions: The lung is the most affected organ in gross examination, histology and polymerase chain reaction. SARS-CoV-2 detection in other organs did not reveal relevant or specific histological changes. Moreover, we did not find CNS involvement.
    MeSH term(s) Aged ; Aged, 80 and over ; Autopsy/statistics & numerical data ; COVID-19/epidemiology ; COVID-19/pathology ; COVID-19/virology ; Central Nervous System/pathology ; Central Nervous System/virology ; Female ; Humans ; Lung/pathology ; Lung/virology ; Lymph Nodes/pathology ; Lymph Nodes/virology ; Male ; Middle Aged ; Viral Load
    Language English
    Publishing date 2021-07-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0254872
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Viral mapping in COVID-19 deceased in the Augsburg autopsy series of the first wave

    Klaus Hirschbühl / Sebastian Dintner / Martin Beer / Claudia Wylezich / Jürgen Schlegel / Claire Delbridge / Lukas Borcherding / Jirina Lippert / Stefan Schiele / Gernot Müller / Dimitra Moiraki / Oliver Spring / Michael Wittmann / Elisabeth Kling / Georg Braun / Thomas Kröncke / Rainer Claus / Bruno Märkl / Tina Schaller

    PLoS ONE, Vol 16, Iss 7, p e

    A multiorgan and multimethodological approach.

    2021  Volume 0254872

    Abstract: Background COVID-19 is only partly understood, and the level of evidence available in terms of pathophysiology, epidemiology, therapy, and long-term outcome remains limited. During the early phase of the pandemic, it was necessary to effectively ... ...

    Abstract Background COVID-19 is only partly understood, and the level of evidence available in terms of pathophysiology, epidemiology, therapy, and long-term outcome remains limited. During the early phase of the pandemic, it was necessary to effectively investigate all aspects of this new disease. Autopsy can be a valuable procedure to investigate the internal organs with special techniques to obtain information on the disease, especially the distribution and type of organ involvement. Methods During the first wave of COVID-19 in Germany, autopsies of 19 deceased patients were performed. Besides gross examination, the organs were analyzed with standard histology and polymerase-chain-reaction for SARS-CoV-2. Polymerase chain reaction positive localizations were further analyzed with immunohistochemistry and RNA-in situ hybridization for SARS-CoV-2. Results Eighteen of 19 patients were found to have died due to COVID-19. Clinically relevant histological changes were only observed in the lungs. Diffuse alveolar damage in considerably different degrees was noted in 18 cases. Other organs, including the central nervous system, did not show specific micromorphological alterations. In terms of SARS-CoV-2 detection, the focus remains on the upper airways and lungs. This is true for both the number of positive samples and the viral load. A highly significant inverse correlation between the stage of diffuse alveolar damage and viral load was found on a case and a sample basis. Mediastinal lymph nodes and fat were also affected by the virus at high frequencies. By contrast, other organs rarely exhibited a viral infection. Moderate to strong correlations between the methods for detecting SARS-CoV-2 were observed for the lungs and for other organs. Conclusions The lung is the most affected organ in gross examination, histology and polymerase chain reaction. SARS-CoV-2 detection in other organs did not reveal relevant or specific histological changes. Moreover, we did not find CNS involvement.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Contamination of personal protective equipment during COVID-19 autopsies

    Brandner, Johanna M / Boor, Peter / Borcherding, Lukas S / Edler, Carolin / Gerber, Sven / Heinemann, Axel / Hilsenbeck, Julia / Kasajima, Atsuko / Lohner, Larissa / Märkl, Bruno / Pablik, Jessica / Schröder, Ann Sophie / Sommer, Linna / Slotta-Huspenina, Julia / Sperhake, Jan-Peter / von Stillfried, Saskia / Dintner, Sebastian

    medRxiv

    Abstract: Confronted with an emerging infectious disease, the medical community faced relevant concerns regarding the performance of autopsies of COVID-19 deceased at the beginning of the pandemic. This attitude has changed, and autopsies are now recognized as ... ...

    Abstract Confronted with an emerging infectious disease, the medical community faced relevant concerns regarding the performance of autopsies of COVID-19 deceased at the beginning of the pandemic. This attitude has changed, and autopsies are now recognized as indispensable tools for elucidating COVID-19; despite this, the true risk of infection for autopsy staff is still debated. To elucidate the rate of SARS-CoV-2 contamination in personal protective equipment (PPE), swabs were taken at nine locations of the PPE of one physician and an assistant each from 11 full autopsies performed at four different centers. Further samples were obtained for three minimally invasive autopsies (MIA) conducted at a fifth center. Lung/bronchus swabs of the deceased served as positive controls. SARS-CoV-2 RNA was detected by RT-qPCR. In 9/11 full autopsies PPE samples were tested RNA positive with PCR, in total 21% of all PPE samples taken. The main contaminated parts of the PPE were the gloves (64% positive), the aprons (50% positive), and the upper sides of shoes (36% positive) while for example the fronts of safety goggles were only positive in 4.5% of the samples and all face masks were negative. In MIA, viral RNA was observed in one sample from a glove, but not in other swabs. Infectious virus isolation in cell culture was performed in RNA positive swabs from full autopsies. Of all RNA positive PPE samples, 21% of the glove samples were positive for infectious virus taken in 3/11 full autopsies. In conclusion, in >80% of autopsies, PPE was contaminated with viral RNA. In >25% of autopsies, PPE was found to be even contaminated with infectious virus, signifying a potential risk of infection among autopsy staff. Adequate PPE and hygiene measures, including appropriate waste deposition, are therefore mandatory to enable safe work environment.
    Keywords covid19
    Language English
    Publishing date 2021-07-15
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2021.07.12.21260357
    Database COVID19

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  7. Article ; Online: Viral mapping in COVID-19 deceased in the Augsburg autopsy series of the first wave

    Hirschbühl, Klaus / Dintner, Sebastian / Beer, Martin / Wylezich, Claudia / Schlegel, Jürgen / Delbridge, Claire / Borcherding, Lukas / Lippert, Jirina / Schiele, Stefan / Müller, Gernot / Moiraki, Dimitra / Spring, Oliver / Wittmann, Michael / Kling, Elisabeth / Braun, Georg / Kröncke, Thomas / Claus, Rainer / Märkl, Bruno / Schaller, Tina

    A multiorgan and multimethodological approach

    2021  

    Abstract: Background: COVID-19 is only partly understood, and the level of evidence available in terms of pathophysiology, epidemiology, therapy, and long-term outcome remains limited. During the early phase of the pandemic, it was necessary to effectively ... ...

    Abstract Background: COVID-19 is only partly understood, and the level of evidence available in terms of pathophysiology, epidemiology, therapy, and long-term outcome remains limited. During the early phase of the pandemic, it was necessary to effectively investigate all aspects of this new disease. Autopsy can be a valuable procedure to investigate the internal organs with special techniques to obtain information on the disease, especially the distribution and type of organ involvement. Methods: During the first wave of COVID-19 in Germany, autopsies of 19 deceased patients were performed. Besides gross examination, the organs were analyzed with standard histology and polymerase-chain-reaction for SARS-CoV-2. Polymerase chain reaction positive localizations were further analyzed with immunohistochemistry and RNA-in situ hybridization for SARS-CoV-2. Results: Eighteen of 19 patients were found to have died due to COVID-19. Clinically relevant histological changes were only observed in the lungs. Diffuse alveolar damage in considerably different degrees was noted in 18 cases. Other organs, including the central nervous system, did not show specific micromorphological alterations. In terms of SARS-CoV-2 detection, the focus remains on the upper airways and lungs. This is true for both the number of positive samples and the viral load. A highly significant inverse correlation between the stage of diffuse alveolar damage and viral load was found on a case and a sample basis. Mediastinal lymph nodes and fat were also affected by the virus at high frequencies. By contrast, other organs rarely exhibited a viral infection. Moderate to strong correlations between the methods for detecting SARS-CoV-2 were observed for the lungs and for other organs. Conclusions: The lung is the most affected organ in gross examination, histology and polymerase chain reaction. SARS-CoV-2 detection in other organs did not reveal relevant or specific histological changes. Moreover, we did not find CNS involvement.
    Keywords Text ; ddc:570 ; COVID 19 -- Autopsy -- Histology -- SARS CoV 2 -- Lungs -- Central nervous system -- Diabetes mellitus -- RNA hybridization
    Subject code 610
    Language English
    Publishing date 2021-07-19
    Publishing country de
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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