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Assessing and improving the validity of COVID-19 autopsy studies - A multicentre approach to establish essential standards for immunohistochemical and ultrastructural analyses

Standard

Assessing and improving the validity of COVID-19 autopsy studies - A multicentre approach to establish essential standards for immunohistochemical and ultrastructural analyses. / Krasemann, Susanne; Dittmayer, Carsten; von Stillfried, Saskia; Meinhardt, Jenny; Heinrich, Fabian; Hartmann, Kristin; Pfefferle, Susanne; Thies, Edda; von Manitius, Regina; Aschman, Tom Alex David; Radke, Josefine; Osterloh, Anja; Schmid, Simone; Buhl, Eva Miriam; Ihlow, Jana; Dubois, Frank; Arnhold, Viktor; Elezkurtaj, Sefer; Horst, David; Hocke, Andreas; Timm, Sara; Bachmann, Sebastian; Corman, Victor; Goebel, Hans-Hilmar; Matschke, Jakob; Stanelle-Bertram, Stephanie; Gabriel, Gülsah; Seilhean, Danielle; Adle-Biassette, Homa; Ondruschka, Benjamin; Ochs, Matthias; Stenzel, Werner; Heppner, Frank L; Boor, Peter; Radbruch, Helena; Laue, Michael; Glatzel, Markus.

in: EBIOMEDICINE, Jahrgang 83, 104193, 09.2022.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Krasemann, S, Dittmayer, C, von Stillfried, S, Meinhardt, J, Heinrich, F, Hartmann, K, Pfefferle, S, Thies, E, von Manitius, R, Aschman, TAD, Radke, J, Osterloh, A, Schmid, S, Buhl, EM, Ihlow, J, Dubois, F, Arnhold, V, Elezkurtaj, S, Horst, D, Hocke, A, Timm, S, Bachmann, S, Corman, V, Goebel, H-H, Matschke, J, Stanelle-Bertram, S, Gabriel, G, Seilhean, D, Adle-Biassette, H, Ondruschka, B, Ochs, M, Stenzel, W, Heppner, FL, Boor, P, Radbruch, H, Laue, M & Glatzel, M 2022, 'Assessing and improving the validity of COVID-19 autopsy studies - A multicentre approach to establish essential standards for immunohistochemical and ultrastructural analyses', EBIOMEDICINE, Jg. 83, 104193. https://doi.org/10.1016/j.ebiom.2022.104193

APA

Krasemann, S., Dittmayer, C., von Stillfried, S., Meinhardt, J., Heinrich, F., Hartmann, K., Pfefferle, S., Thies, E., von Manitius, R., Aschman, T. A. D., Radke, J., Osterloh, A., Schmid, S., Buhl, E. M., Ihlow, J., Dubois, F., Arnhold, V., Elezkurtaj, S., Horst, D., ... Glatzel, M. (2022). Assessing and improving the validity of COVID-19 autopsy studies - A multicentre approach to establish essential standards for immunohistochemical and ultrastructural analyses. EBIOMEDICINE, 83, [104193]. https://doi.org/10.1016/j.ebiom.2022.104193

Vancouver

Krasemann S, Dittmayer C, von Stillfried S, Meinhardt J, Heinrich F, Hartmann K et al. Assessing and improving the validity of COVID-19 autopsy studies - A multicentre approach to establish essential standards for immunohistochemical and ultrastructural analyses. EBIOMEDICINE. 2022 Sep;83. 104193. https://doi.org/10.1016/j.ebiom.2022.104193

Bibtex

@article{40db68b24a6f49b1ac2b8ec019c774fa,
title = "Assessing and improving the validity of COVID-19 autopsy studies - A multicentre approach to establish essential standards for immunohistochemical and ultrastructural analyses",
abstract = "BACKGROUND: Autopsy studies have provided valuable insights into the pathophysiology of COVID-19. Controversies remain about whether the clinical presentation is due to direct organ damage by SARS-CoV-2 or secondary effects, such as overshooting immune response. SARS-CoV-2 detection in tissues by RT-qPCR and immunohistochemistry (IHC) or electron microscopy (EM) can help answer these questions, but a comprehensive evaluation of these applications is missing.METHODS: We assessed publications using IHC and EM for SARS-CoV-2 detection in autopsy tissues. We systematically evaluated commercially available antibodies against the SARS-CoV-2 proteins in cultured cell lines and COVID-19 autopsy tissues. In a multicentre study, we evaluated specificity, reproducibility, and inter-observer variability of SARS-CoV-2 IHC. We correlated RT-qPCR viral tissue loads with semiquantitative IHC scoring. We used qualitative and quantitative EM analyses to refine criteria for ultrastructural identification of SARS-CoV-2.FINDINGS: Publications show high variability in detection and interpretation of SARS-CoV-2 abundance in autopsy tissues by IHC or EM. We show that IHC using antibodies against SARS-CoV-2 nucleocapsid yields the highest sensitivity and specificity. We found a positive correlation between presence of viral proteins by IHC and RT-qPCR-determined SARS-CoV-2 viral RNA load (N= 35; r=-0.83, p-value <0.0001). For EM, we refined criteria for virus identification and provide recommendations for optimized sampling and analysis. 135 of 144 publications misinterpret cellular structures as virus using EM or show only insufficient data. We provide publicly accessible digitized EM sections as a reference and for training purposes.INTERPRETATION: Since detection of SARS-CoV-2 in human autopsy tissues by IHC and EM is difficult and frequently incorrect, we propose criteria for a re-evaluation of available data and guidance for further investigations of direct organ effects by SARS-CoV-2.FUNDING: German Federal Ministry of Health, German Federal Ministry of Education and Research, Berlin University Alliance, German Research Foundation, German Center for Infectious Research.",
author = "Susanne Krasemann and Carsten Dittmayer and {von Stillfried}, Saskia and Jenny Meinhardt and Fabian Heinrich and Kristin Hartmann and Susanne Pfefferle and Edda Thies and {von Manitius}, Regina and Aschman, {Tom Alex David} and Josefine Radke and Anja Osterloh and Simone Schmid and Buhl, {Eva Miriam} and Jana Ihlow and Frank Dubois and Viktor Arnhold and Sefer Elezkurtaj and David Horst and Andreas Hocke and Sara Timm and Sebastian Bachmann and Victor Corman and Hans-Hilmar Goebel and Jakob Matschke and Stephanie Stanelle-Bertram and G{\"u}lsah Gabriel and Danielle Seilhean and Homa Adle-Biassette and Benjamin Ondruschka and Matthias Ochs and Werner Stenzel and Heppner, {Frank L} and Peter Boor and Helena Radbruch and Michael Laue and Markus Glatzel",
note = "Copyright {\textcopyright} 2022 The Author(s). Published by Elsevier B.V. All rights reserved.",
year = "2022",
month = sep,
doi = "10.1016/j.ebiom.2022.104193",
language = "English",
volume = "83",
journal = "EBIOMEDICINE",
issn = "2352-3964",
publisher = "Elsevier BV",

}

RIS

TY - JOUR

T1 - Assessing and improving the validity of COVID-19 autopsy studies - A multicentre approach to establish essential standards for immunohistochemical and ultrastructural analyses

AU - Krasemann, Susanne

AU - Dittmayer, Carsten

AU - von Stillfried, Saskia

AU - Meinhardt, Jenny

AU - Heinrich, Fabian

AU - Hartmann, Kristin

AU - Pfefferle, Susanne

AU - Thies, Edda

AU - von Manitius, Regina

AU - Aschman, Tom Alex David

AU - Radke, Josefine

AU - Osterloh, Anja

AU - Schmid, Simone

AU - Buhl, Eva Miriam

AU - Ihlow, Jana

AU - Dubois, Frank

AU - Arnhold, Viktor

AU - Elezkurtaj, Sefer

AU - Horst, David

AU - Hocke, Andreas

AU - Timm, Sara

AU - Bachmann, Sebastian

AU - Corman, Victor

AU - Goebel, Hans-Hilmar

AU - Matschke, Jakob

AU - Stanelle-Bertram, Stephanie

AU - Gabriel, Gülsah

AU - Seilhean, Danielle

AU - Adle-Biassette, Homa

AU - Ondruschka, Benjamin

AU - Ochs, Matthias

AU - Stenzel, Werner

AU - Heppner, Frank L

AU - Boor, Peter

AU - Radbruch, Helena

AU - Laue, Michael

AU - Glatzel, Markus

N1 - Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.

PY - 2022/9

Y1 - 2022/9

N2 - BACKGROUND: Autopsy studies have provided valuable insights into the pathophysiology of COVID-19. Controversies remain about whether the clinical presentation is due to direct organ damage by SARS-CoV-2 or secondary effects, such as overshooting immune response. SARS-CoV-2 detection in tissues by RT-qPCR and immunohistochemistry (IHC) or electron microscopy (EM) can help answer these questions, but a comprehensive evaluation of these applications is missing.METHODS: We assessed publications using IHC and EM for SARS-CoV-2 detection in autopsy tissues. We systematically evaluated commercially available antibodies against the SARS-CoV-2 proteins in cultured cell lines and COVID-19 autopsy tissues. In a multicentre study, we evaluated specificity, reproducibility, and inter-observer variability of SARS-CoV-2 IHC. We correlated RT-qPCR viral tissue loads with semiquantitative IHC scoring. We used qualitative and quantitative EM analyses to refine criteria for ultrastructural identification of SARS-CoV-2.FINDINGS: Publications show high variability in detection and interpretation of SARS-CoV-2 abundance in autopsy tissues by IHC or EM. We show that IHC using antibodies against SARS-CoV-2 nucleocapsid yields the highest sensitivity and specificity. We found a positive correlation between presence of viral proteins by IHC and RT-qPCR-determined SARS-CoV-2 viral RNA load (N= 35; r=-0.83, p-value <0.0001). For EM, we refined criteria for virus identification and provide recommendations for optimized sampling and analysis. 135 of 144 publications misinterpret cellular structures as virus using EM or show only insufficient data. We provide publicly accessible digitized EM sections as a reference and for training purposes.INTERPRETATION: Since detection of SARS-CoV-2 in human autopsy tissues by IHC and EM is difficult and frequently incorrect, we propose criteria for a re-evaluation of available data and guidance for further investigations of direct organ effects by SARS-CoV-2.FUNDING: German Federal Ministry of Health, German Federal Ministry of Education and Research, Berlin University Alliance, German Research Foundation, German Center for Infectious Research.

AB - BACKGROUND: Autopsy studies have provided valuable insights into the pathophysiology of COVID-19. Controversies remain about whether the clinical presentation is due to direct organ damage by SARS-CoV-2 or secondary effects, such as overshooting immune response. SARS-CoV-2 detection in tissues by RT-qPCR and immunohistochemistry (IHC) or electron microscopy (EM) can help answer these questions, but a comprehensive evaluation of these applications is missing.METHODS: We assessed publications using IHC and EM for SARS-CoV-2 detection in autopsy tissues. We systematically evaluated commercially available antibodies against the SARS-CoV-2 proteins in cultured cell lines and COVID-19 autopsy tissues. In a multicentre study, we evaluated specificity, reproducibility, and inter-observer variability of SARS-CoV-2 IHC. We correlated RT-qPCR viral tissue loads with semiquantitative IHC scoring. We used qualitative and quantitative EM analyses to refine criteria for ultrastructural identification of SARS-CoV-2.FINDINGS: Publications show high variability in detection and interpretation of SARS-CoV-2 abundance in autopsy tissues by IHC or EM. We show that IHC using antibodies against SARS-CoV-2 nucleocapsid yields the highest sensitivity and specificity. We found a positive correlation between presence of viral proteins by IHC and RT-qPCR-determined SARS-CoV-2 viral RNA load (N= 35; r=-0.83, p-value <0.0001). For EM, we refined criteria for virus identification and provide recommendations for optimized sampling and analysis. 135 of 144 publications misinterpret cellular structures as virus using EM or show only insufficient data. We provide publicly accessible digitized EM sections as a reference and for training purposes.INTERPRETATION: Since detection of SARS-CoV-2 in human autopsy tissues by IHC and EM is difficult and frequently incorrect, we propose criteria for a re-evaluation of available data and guidance for further investigations of direct organ effects by SARS-CoV-2.FUNDING: German Federal Ministry of Health, German Federal Ministry of Education and Research, Berlin University Alliance, German Research Foundation, German Center for Infectious Research.

U2 - 10.1016/j.ebiom.2022.104193

DO - 10.1016/j.ebiom.2022.104193

M3 - SCORING: Journal article

C2 - 35930888

VL - 83

JO - EBIOMEDICINE

JF - EBIOMEDICINE

SN - 2352-3964

M1 - 104193

ER -