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2022-08-02Zeitschriftenartikel
Assessing and improving the validity of COVID-19 autopsy studies - A multicentre approach to establish essential standards for immunohistochemical and ultrastructural analyses
dc.contributor.authorKrasemann, Susanne
dc.contributor.authorDittmayer, Carsten
dc.contributor.authorvon Stillfried, Saskia
dc.contributor.authorMeinhardt, Jenny
dc.contributor.authorHeinrich, Fabian
dc.contributor.authorHartmann, Kristin
dc.contributor.authorPfefferle, Susanne
dc.contributor.authorThies, Edda
dc.contributor.authorvon Manitius, Regina
dc.contributor.authorAschman, Tom Alex David
dc.contributor.authorRadke, Josefine
dc.contributor.authorOsterloh, Anja
dc.contributor.authorSchmid, Simone
dc.contributor.authorBuhl, Eva Miriam
dc.contributor.authorIhlow, Jana
dc.contributor.authorDubois, Frank
dc.contributor.authorArnhold, Viktor
dc.contributor.authorElezkurtaj, Sefer
dc.contributor.authorHorst, David
dc.contributor.authorHocke, Andreas
dc.contributor.authorGlatzel, Markus
dc.date.accessioned2024-09-12T15:30:39Z
dc.date.available2024-09-12T15:30:39Z
dc.date.issued2022-08-02none
dc.identifier.other10.1016/j.ebiom.2022.104193
dc.identifier.urihttp://edoc.rki.de/176904/12161
dc.description.abstractBackground 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.eng
dc.language.isoengnone
dc.publisherRobert Koch-Institut
dc.rights(CC BY-NC-ND 3.0 DE) Namensnennung - Nicht-kommerziell - Keine Bearbeitung 3.0 Deutschlandger
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/de/
dc.subjectSARS-CoV-2eng
dc.subjectCOVID-19eng
dc.subjectautopsyeng
dc.subjectimmunohistochemistryeng
dc.subjectelectron microscopyeng
dc.subjectpathologyeng
dc.subject.ddc610 Medizin und Gesundheitnone
dc.titleAssessing and improving the validity of COVID-19 autopsy studies - A multicentre approach to establish essential standards for immunohistochemical and ultrastructural analysesnone
dc.typearticle
dc.identifier.urnurn:nbn:de:0257-176904/12161-1
dc.type.versionpublishedVersionnone
local.edoc.container-titleeBio Medicinenone
local.edoc.container-issn2352-3964none
local.edoc.pages16none
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttps://www.sciencedirect.com/journal/ebiomedicinenone
local.edoc.container-publisher-nameElseviernone
local.edoc.container-volume83none
local.edoc.container-reportyear2022none
dc.description.versionPeer Reviewednone

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