Human kidney is a target for novel severe acute respiratory syndrome coronavirus 2 infection

  1. Bo Diao
  2. Chenhui Wang
  3. Rongshuai Wang
  4. Zeqing Feng
  5. Ji Zhang
  6. Han Yang
  7. Yingjun Tan
  8. Huiming Wang
  9. Changsong Wang
  10. Liang Liu
  11. Ying Liu
  12. Yueping Liu
  13. Gang Wang
  14. Zilin Yuan
  15. Xiaotao Hou
  16. Liang Ren
  17. Yuzhang Wu
  18. Yongwen Chen

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Abstract

It is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly infect human kidney, thus leading to acute kidney injury (AKI). Here, we perform a retrospective analysis of clinical parameters from 85 patients with laboratory-confirmed coronavirus disease 2019 (COVID-19); moreover, kidney histopathology from six additional COVID-19 patients with post-mortem examinations was performed. We find that 27% (23/85) of patients exhibited AKI. The elderly patients and cases with comorbidities (hypertension and heart failure) are more prone to develop AKI. Haematoxylin & eosin staining shows that the kidneys from COVID-19 autopsies have moderate to severe tubular damage. In situ hybridization assays illustrate that viral RNA accumulates in tubules. Immunohistochemistry shows nucleocapsid and spike protein deposits in the tubules, and immunofluorescence double staining shows that both antigens are restricted to the angiotensin converting enzyme-II-positive tubules. SARS-CoV-2 infection triggers the expression of hypoxic damage-associated molecules, including DP2 and prostaglandin D synthase in infected tubules. Moreover, it enhances CD68+ macrophages infiltration into the tubulointerstitium, and complement C5b-9 deposition on tubules is also observed. These results suggest that SARS-CoV-2 directly infects human kidney to mediate tubular pathogenesis and AKI.

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  1. Version published to 10.1038/s41467-021-22781-1
  2. ScreenIT

    SciScore for 10.1101/2020.03.04.20031120: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Written informed consent was waived by the Ethics Commission of the designated hospital for emerging infectious diseases.
    IRB: Written informed consent was waived by the Ethics Commission of the designated hospital for emerging infectious diseases.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The sections were then incubated overnight at 4 °C with primary anti-SARS-CoV-2 nucleocaspid protein (NP) antibodies (clone ID: 019, 1:100, rabbit IgG; Sino Biological,
    anti-SARS-CoV-2 nucleocaspid protein (NP
    suggested: None
    rabbit IgG
    suggested: None
    Beijing), anti-CD8 (Clone ID:4B11, 1:100, mouse IgG2b; BIO-RAD), anti-CD68 (Clone ID:KP1, 1:100, mouse IgG1; BIO-RAD), anti-CD56 (Clone ID:123C3, 1:100, mouse IgG1; BIO-RAD), anti-C5b-9 (clone ID: aE11, 1:100, mouse IgG; Dakocytomation) or rabbit-isotype antibody controls (1:100; Dako).
    anti-CD8
    suggested: (Thermo Fisher Scientific Cat# MA1-42129, RRID:AB_2537281)
    anti-CD68
    suggested: None
    anti-CD56
    suggested: None
    anti-C5b-9
    suggested: (LSBio (LifeSpan Cat# LS-C128311-100, RRID:AB_10833506)
    mouse IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analysis: Statistical analyses were performed using GraphPad Prism version 8.0 (GraphPad Software, Inc.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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 10.1101/2020.03.04.20031120 on medRxiv