Two distinct immunopathological profiles in autopsy lungs of COVID-19

  1. Ronny Nienhold
  2. Yari Ciani
  3. Viktor H. Koelzer
  4. Alexandar Tzankov
  5. Jasmin D. Haslbauer
  6. Thomas Menter
  7. Nathalie Schwab
  8. Maurice Henkel
  9. Angela Frank
  10. Veronika Zsikla
  11. Niels Willi
  12. Werner Kempf
  13. Thomas Hoyler
  14. Mattia Barbareschi
  15. Holger Moch
  16. Markus Tolnay
  17. Gieri Cathomas
  18. Francesca Demichelis
  19. Tobias Junt
  20. Kirsten D. Mertz

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Abstract

Coronavirus Disease 19 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has grown to a worldwide pandemic with substantial mortality. Immune mediated damage has been proposed as a pathogenic factor, but immune responses in lungs of COVID-19 patients remain poorly characterized. Here we show transcriptomic, histologic and cellular profiles of post mortem COVID-19 ( n  = 34 tissues from 16 patients) and normal lung tissues ( n  = 9 tissues from 6 patients). Two distinct immunopathological reaction patterns of lethal COVID-19 are identified. One pattern shows high local expression of interferon stimulated genes (ISG high ) and cytokines, high viral loads and limited pulmonary damage, the other pattern shows severely damaged lungs, low ISGs (ISG low ), low viral loads and abundant infiltrating activated CD8 + T cells and macrophages. ISG high patients die significantly earlier after hospitalization than ISG low patients. Our study may point to distinct stages of progression of COVID-19 lung disease and highlights the need for peripheral blood biomarkers that inform about patient lung status and guide treatment.

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    SciScore for 10.1101/2020.06.17.20133637: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethics approval was obtained from the Ethics Committee of Northwestern and Central Switzerland (Project-ID 2020-00629).
    Consent: For all patients, either personal and/or family consent was obtained for autopsy and sample collection.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Our study has several limitations. The fact that patients with the innate / ISGhigh stage die early while patients with the lymphocytic / ISGlow profile die late after hospitalization, together with knowledge about the immune reaction against other coronaviruses, strongly suggests that COVID-19 lung disease progresses from an ISGhigh to an ISGlow stage. However, an autopsy study is, by design, not longitudinal. Therefore we do not have formal proof that all COVID-19 infected ISGlow lungs have undergone a previous ISGhigh stage. Also, it is unknown why some patients die early and others late. In addition, our focus on the lung only allowed us to investigate pulmonary factors of patient mortality, i.e. an overshooting innate immune activation with IAH in both ISGhigh and ISGlow cases and DAD in ISGlow cases. No reported cause of death was enriched in ISGhigh or ISGlow patients, and multi-organ failure was reported as a cause of death only for two of our patients. Another limitation is that we lack gene expression data from blood of autopsy patients or serological data at the time of death. Therefore we were not able to identify peripheral biomarkers predicting specific immunological profiles in the lung. Finally, we analyzed our lungs with a focused gene expression set since quality and quantity of autopsy-derived RNA is often insufficient for unbiased methods. In spite of this technical limitation, which restricted our analysis, we were able to uncover two novel and distinct i...

    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.

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  2. Version published to 10.1038/s41467-020-18854-2
  3. Version published to 10.1101/2020.06.17.20133637v2 on medRxiv
  4. Version published to 10.1101/2020.06.17.20133637v1 on medRxiv