High estradiol and low testosterone levels are associated with critical illness in male but not in female COVID-19 patients: a retrospective cohort study

  1. Maria Schroeder
  2. Berfin Schaumburg
  3. Zacharias Mueller
  4. Ann Parplys
  5. Dominik Jarczak
  6. Kevin Roedl
  7. Axel Nierhaus
  8. Geraldine de Heer
  9. Joern Grensemann
  10. Bettina Schneider
  11. Fabian Stoll
  12. Tian Bai
  13. Henning Jacobsen
  14. Martin Zickler
  15. Stephanie Stanelle-Bertram
  16. Kristin Klaetschke
  17. Thomas Renné
  18. Andreas Meinhardt
  19. Jens Aberle
  20. Jens Hiller
  21. Sven Peine
  22. Lothar Kreienbrock
  23. Karin Klingel
  24. Stefan Kluge
  25. Guelsah Gabriel

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Abstract

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  1. Version published to 10.1080/22221751.2021.1969869
  2. ScreenIT

    SciScore for 10.1101/2020.05.07.20073817: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethics statement: Sampling from laboratory-confirmed Covid-19 patients was reviewed and approved by the ethics committee at the Hamburg State Chamber of Physicians (registration no.: WF-053/20).
    Consent: The need for an informed consent for healthy blood donors (HC) and patients with coronary heart diseases (CHD) was waived by the ethics committee because data were retrieved retrospectively from electronic health records.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableA total of 39 male and 11 female patients were included in this study.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Pathway analysis was done using the KEGG database as provided by the Metaboanalyst implementation, using a hypergeometric test.
    KEGG
    suggested: (KEGG, RRID:SCR_012773)
    Metaboanalyst
    suggested: (MetaboAnalyst, RRID:SCR_015539)
    All statistical evaluations mentioned above were performed with SAS®, version 9.4 TS level 1M5 (SAS Institute Inc.
    SAS®
    suggested: (SASqPCR, RRID:SCR_003056)
    SAS Institute
    suggested: (Statistical Analysis System, RRID:SCR_008567)
    2 (GraphPad Software, Inc.).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    However, the low female Covid-19 cohort size in our study is a potential limitation with respect to conclusions on female Covid-19 outcome. This was due to the fact that more men than women were admitted to the ICU in the time period of recruitment further highlighting the importance of sex on critical Covid-19 outcome. Despite these limitations in the female Covid-19 cohort, other postulated an elevated Covid-19 risk for women with polycystic ovary syndrome (PCOS), a condition characterized by increased androgen levels 26. This highlights the need for further investigations to understand the impact of elevated testosterone levels in women in the context of Covid-19. Second, we found that similar to males, female Covid-19 patients also present elevated estradiol levels. This is in contrast to the findings in the female SARS-CoV-2 golden hamster model using young, lean and comorbidity-free animals 4. Thus, future in depth investigations are required to understand the role of estradiol in postmenopausal Covid-19 patients. One possible investigation line might be to analyze whether elevated female testosterone levels might provide a substrate for the CYP19A1 aromatase resulting in elevated estradiol levels in at-risk postmenopausal women upon SARS-CoV-2 infection. However, elevated estradiol levels seem to be a risk factor for severe Covid-19 outcome in male and female patients. Male Covid-19 patients on the other hand, additionally suffer from severely depleted testosterone and...

    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.

    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 10.1101/2020.05.07.20073817 on medRxiv