SARS‐CoV‐2‐specific humoral and cellular immunity in two renal transplants and two hemodialysis patients treated with convalescent plasma

  1. Monika Lindemann
  2. Adalbert Krawczyk
  3. Sebastian Dolff
  4. Margarethe Konik
  5. Hana Rohn
  6. Maximillian Platte
  7. Laura Thümmler
  8. Sina Schwarzkopf
  9. Leonie Schipper
  10. Maren Bormann
  11. Lukas van de Sand
  12. Marianne Breyer
  13. Hannes Klump
  14. Dietmar Knop
  15. Veronika Lenz
  16. Christian Temme
  17. Ulf Dittmer
  18. Peter A. Horn
  19. Oliver Witzke

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Abstract

When patients with chronic kidney disease are infected with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) they can face two specific problems: virus‐specific immune responses may be impaired and remdesivir, an antiviral drug described to shorten recovery, is contraindicated. Antiviral treatment with convalescent plasma (CP) could be an alternative treatment option. In this case report, we present two kidney transplant recipients and two hemodialysis patients who were infected with SARS‐CoV‐2 and received CP. Antibodies against the receptor‐binding domain in the S1 subunit of the SARS‐CoV‐2 spike protein were determined sequentially by immunoglobulin G (IgG) enzyme‐linked immunosorbent assay (ELISA) and neutralization assay and specific cellular responses by interferon‐gamma ELISpot. Before treatment, in both kidney transplant recipients and one hemodialysis patient antibodies were undetectable by ELISA (ratio < 1.1), corresponding to low neutralizing antibody titers (≤1:40). ELISpot responses in the four patients were either weak or absent. After CP treatment, we observed an increase of SARS‐CoV‐2‐specific antibodies (IgG ratio and neutralization titer) and of specific cellular responses. After intermittent clinical improvement, one kidney transplant recipient again developed typical symptoms on Day 12 after treatment and received a second cycle of CP treatment. Altogether, three patients clinically improved and could be discharged from the hospital. However, one 83‐year‐old multimorbid patient deceased. Our data suggest that the success of CP therapy may only be temporary in patients with chronic kidney disease; which requires close monitoring of viral load and antiviral immunity and possibly an adaptation of the treatment regimen.

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  1. Version published to 10.1002/jmv.26840
  2. ScreenIT

    SciScore for 10.1101/2020.12.09.20239673: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The study was approved by the institutional review board of the University Hospital Essen, Germany (20-9256-BO for the patients and 20-9225-BO for the donors) and the study participants provided written informed consent.
    Consent: All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Antibody ELISA: To assess SARS-CoV-2-specific humoral immunity, IgG antibodies were determined by a CE marked Anti-SARS-CoV-2 IgG semi-quantitative ELISA (Euroimmun, Lübeck, Germany), according to the manufacturer’s instructions.
    IgG
    suggested: None
    Anti-SARS-CoV-2 IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Serial dilutions (1:20 to 1:1280) of the respective sera were pre-incubated with 100 TCID50 of SARS-CoV-2 for one hour at 37°C and added afterwards to confluent Vero E6 cells cultured in 96-well microtiter plates.
    Vero E6
    suggested: None

    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 10.1101/2020.12.09.20239673v1 on medRxiv