High viral loads: what drives fatal cases of COVID-19 in vaccinees? – an autopsy study

  1. Klaus Hirschbühl
  2. Tina Schaller
  3. Bruno Märkl
  4. Rainer Claus
  5. Eva Sipos
  6. Lukas Rentschler
  7. Andrea Maccagno
  8. Bianca Grosser
  9. Elisabeth Kling
  10. Michael Neidig
  11. Thomas Kröncke
  12. Oliver Spring
  13. Georg Braun
  14. Hans Bösmüller
  15. Maximilian Seidl
  16. Irene Esposito
  17. Jessica Pablik
  18. Julia Hilsenbeck
  19. Peter Boor
  20. Martin Beer
  21. Sebastian Dintner
  22. Claudia Wylezich

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Abstract

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  1. Version published to 10.1038/s41379-022-01069-9
  2. ScreenIT

    SciScore for 10.1101/2021.12.03.21267155: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: Written consent was obtained from the next of kin.
    IRB: This study was approved by the internal review board of the medical center-Augsburg (BKF No. 2020–18) and the ethics committee of the University of Munich (Project number 20–426, COVID-19 registry of the University hospital Augsburg, the ethics committee of University Dresden (BO-EK-175052020), the ethics committee of University Düsseldorf (2020-971), and the ethics committee of University Tübingen (236/2021BO2).
    Field Sample Permit: Autopsy, Sample Collection, and Histology: The techniques of autopsy and histology workup have been described previously (17).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    In addition, the obtained SARS-CoV-2 genome sequences were aligned together and with sequences retrieved from GenBank using MAFFT version 7.388 (37) as implemented in Geneious version 10.2.3 (Biomatters, Auckland, New Zealand).
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)
    Geneious
    suggested: (Geneious, RRID:SCR_010519)
    Phylogenetic trees were constructed using PhyML version 3.0 (38), using the GTR + GAMMA + I model with 100 bootstrap replications, and MrBayes version 3.2.6 (39), using the GTR model with eight rate categories and a proportion of invariable sites in the Geneious software package.
    PhyML
    suggested: (PhyML, RRID:SCR_014629)
    MrBayes
    suggested: (MrBayes, RRID:SCR_012067)
    All tests were performed using the Sigma Plot software package 13.0 (Systat, San Jose, CA, USA).
    Sigma Plot
    suggested: (SigmaPlot, RRID:SCR_003210)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    A general limitation of autopsy studies like ours is the rather small case number. In an ongoing pandemic, inhomogeneities regarding the included variants might further weaken the study. Nevertheless, the consecutively collected cases with an appropriate rate can be assumed to be representative enough to draw relevant conclusions. Overall, this is the first series of fatal courses of COVID-19 after vaccination that was analyzed in detail using a broad range of diagnostic techniques. As a major outcome, it can be concluded that most of the deceased were elderly patients with a high number of comorbidities. Lethal SARS-CoV-2 infection in vaccinated individuals therefore seems to be a very rare event and is mainly connected with a high age and additional underlying factors, such as chronic diseases. A high viral affection, both in terms of the spread within the organism and viral load, together with high rates of immunocompromising conditions, are the most striking findings of this study that were accentuated in cases with an incomplete vaccination status.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.12.03.21267155 on medRxiv