SARS-CoV-2 Antibody Response in Patients Undergoing Kidney Transplantation

  1. Michelle Lubetzky
  2. Ashley Sukhu
  3. Zhen Zhao
  4. Sophie Rand
  5. Vijay Sharma
  6. Samuel Sultan
  7. Zoe Kapur
  8. Shady Albakry
  9. Nataliya Hauser
  10. Jehona Marku-Podvorica
  11. Rebecca Craig-Schapiro
  12. John R. Lee
  13. Thalia Salinas
  14. Meredith Aull
  15. Sandip Kapur
  16. Melissa Cushing
  17. Darshana M. Dadhania

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Abstract

The response of the immune system to COVID-19 in end stage kidney disease patients who undergo kidney transplantation has yet to be described. We report data on 72 patients who underwent SARS-CoV-2 antibody testing both before and after kidney transplantation and were followed for a median of 186 days (range 83, 277). Of the 25 patients with a positive antibody test at the time of transplant, 17 (68%) remained positive after transplantation. Patients were significantly more likely to have a persistently positive test if they reported a symptomatic COVID-19 infection prior to transplant (p=0.01). SARS-CoV-2 IgG index values were measured in a subset of kidney transplant recipients and compared to wait -listed dialysis patients. These assays demonstrated a more significant decline in IgG (58% versus 14% p = 0.008) in transplant recipients when compared to dialysis patients tested during the same time period. Additional analysis of the quality of the immune response measuring the binding of SARS-CoV-2 antibodies to the receptor-binding domain (RBD binding), the antibody neutralizing capability, and the antibody avidity demonstrated a more pronounced effect when comparing pre-transplant values to post-induction therapy/post transplant values. The attenuated IgG response seen in transplant patients compared to dialysis patients after induction therapy requires further study. These data have important implications for post-transplant management of vaccinated dialysis patients.

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  1. ScreenIT

    SciScore for 10.1101/2021.07.25.21261066: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Patient Cohorts, Data Collection and Analysis: This study was approved by the Weill Cornell Medicine Institutional Review Board protocol # 1207012637 entitled Utilizing a Transplant Database for Quality Assessment and Performance Improvement and Clinical Outcomes and protocol # 20-05022154 entitled Impact of COVID-19 Illness on Kidney Transplant Candidates and Recipients.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Laboratory Evaluation: SARS-CoV-2 Antibody Testing: All patients in the study were initially screened for SARS-CoV-2 antibodies upon admission for kidney transplant in the clinical setting using a clinically validated test targeting the RBD of the S1 spike protein (S-RBD) to detect SARS-CoV-2 antibodies which gives either a positive or negative result.
    SARS-CoV-2
    suggested: None
    Testing for the quantitative 10 transplant recipients and 4 dialysis patients testing was performed using the following assays: 1) measurement of IgG Index value and IgM Index value using the SARS-CoV-2 Pylon 3D analyzer (ET Healthcare) as previously described6, 2) SARS-CoV-2 total receptor binding domain (RBD) assay to measure the overall binding between SARS-CoV-2 antibodies and the RBD of the virus S protein, 3) SARS-CoV-2 Antibody Avidity Assay that measures the rate of SARS-CoV-2 specific antibody dissociation from RBD, which is inversely correlated with the antibody avidity, and 4) SARS-CoV-2 Surrogate Neutralizing Antibody Assay (SNAb) which is a competitive binding assay that measures the percentage of RBD-ACE2 binding and inversely correlates with the SNAb binding inhibition (neutralizing activity).
    SARS-CoV-2 total receptor binding domain (RBD
    suggested: None
    Software and Algorithms
    SentencesResources
    Testing for the quantitative 10 transplant recipients and 4 dialysis patients testing was performed using the following assays: 1) measurement of IgG Index value and IgM Index value using the SARS-CoV-2 Pylon 3D analyzer (ET Healthcare) as previously described6, 2) SARS-CoV-2 total receptor binding domain (RBD) assay to measure the overall binding between SARS-CoV-2 antibodies and the RBD of the virus S protein, 3) SARS-CoV-2 Antibody Avidity Assay that measures the rate of SARS-CoV-2 specific antibody dissociation from RBD, which is inversely correlated with the antibody avidity, and 4) SARS-CoV-2 Surrogate Neutralizing Antibody Assay (SNAb) which is a competitive binding assay that measures the percentage of RBD-ACE2 binding and inversely correlates with the SNAb binding inhibition (neutralizing activity).
    ET Healthcare
    suggested: None
    Statistical Analysis: GraphPad Prism 9 was used to determine median, mean and standard deviation for all data.
    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:
    Our data set has several limitations. First, there were only a small number of samples that were available for sequential testing and there was only a short duration of follow-up. In the cohort of patients who underwent quantitative and qualitative testing, all received lymphocyte depleting induction therapy and therefore it is unknown whether results would be similar if patients had another type of induction therapy, nor could we compare whether the attenuated response would also be seen in patients who underwent induction with IL-2 receptor blocking agents. Such data is important as some have suggested using less potent immunosuppression, especially for induction therapy in the COVID era. Finally, dialysis patients are known to have an impaired immune response21 and therefore the study would be strengthened by having a non dialysis cohort to compare our findings as well. It is reassuring, however, that overall our findings mirror that done by other centers in both transplant and non-transplant patients. Overall, this is the first study to describe the changes in humoral immunity in kidney transplant recipients pre and post-transplantation. We have demonstrated that (1) there is significant heterogeneity in the durability of the humoral response to SARS-CoV-2 in the transplant population and (2) transplant patients experience a significantly greater decrease in IgG levels directed against SARS-CoV-2 RBD protein during the first year as compared to wait-listed dialysis patien...

    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.
    • Thank you for including a protocol registration statement.

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

    About SciScore

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  2. Version published to 10.1101/2021.07.25.21261066v1 on medRxiv