Serological Response in Lung Transplant Recipients after Two Doses of SARS-CoV-2 mRNA Vaccines

  1. Madhusudhanan Narasimhan
  2. Lenin Mahimainathan
  3. Andrew E Clark
  4. Amena Usmani
  5. Jing Cao
  6. Ellen Araj
  7. Fernando Torres
  8. Ravi Sarode
  9. Vaidehi Kaza
  10. Chantale Lacelle
  11. Alagarraju Muthukumar

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Abstract

Background: Lung-transplant (LT) recipients are at high risk for COVID-19 due to immunosuppression and respiratory tropism of SARS-CoV-2. The information on the effect of COVID-19 mRNA vaccines to elicit immunogenic responses after a two-dose (2D) regimen in LT recipients is sparse. Thus, we assessed the effect of Pfizer-BioNTech and Moderna mRNA vaccines’ 2D regimen on anti-spike responses in immunocompromised LT recipients. Methods: We utilized serum samples from LT recipients vaccinated for SARS-CoV-2 with 2D of either the Pfizer-BioNTech or Moderna vaccines and 2D-vaccinated naïve (non-transplanted and non-exposed to COVID-19) group. Antibody responses were assessed using the FDA-approved SARS-CoV-2 anti-nucleocapsid protein IgG assay (IgGNC), the SARS-CoV-2 anti-spike protein IgM assay (IgMSP), and the SARS-CoV-2 anti-spike protein IgG II assay (IgGSP). CD4+ T-cell activity was assessed as a marker of immune competence using the ImmuKnow® assay. Results: About 25% (18/73) of SARS-CoV-2 uninfected-LT patients generated a positive spike-IgG response following 2D of vaccines, with 36% (9/25) in the Moderna cohort and only 19% (9/48) in the Pfizer cohort. 2D in LT patients elicited a significantly lesser median IgGSP response (1.7 AU/mL, 95% CI: 0.6–7.5 AU/mL) compared to non-transplanted, uninfected naïve subjects (14,209 AU/mL, 95% CI: 11,261–18,836 AU/mL; p < 0.0001). In LT patients, the Moderna-evoked seropositivity trend was higher than Pfizer. Conclusion: 2D COVID-19 vaccination elicits a dampened serological response in LT patients. Whether assessing other arms of host immunity combined with a higher vaccine dose can better capture and elicit improved immunogenicity in this immunocompromised population warrants investigation.

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  1. Version published to 10.3390/vaccines9070708
  2. ScreenIT

    SciScore for 10.1101/2021.04.26.21255926: (What is this?)

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

    Table 1: Rigor

    EthicsField Sample Permit: This study involved no specific collection of samples.
    IRB: The University of Texas Southwestern Medical Center’s Institutional Review Board granted a waiver of consent for this study.
    Consent: The University of Texas Southwestern Medical Center’s Institutional Review Board granted a waiver of consent for this study.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Antibody responses were semi-quantitatively assessed using serum samples analyzed on the Alinity i platform (Abbott Laboratories, Abbott Park, IL) using the FDA-approved SARS-CoV-2 anti-nucleocapsid protein IgG assay (IgGNC), the SARS-CoV-2 anti-spike protein IgM assay (IgMSP), or the SARS-CoV-2 anti-spike protein IgG II assay (IgGSP) as previously described.
    FDA-approved SARS-CoV-2 anti-nucleocapsid protein IgG
    suggested: None
    anti-spike protein IgM assay (IgMSP)
    suggested: None
    anti-spike protein IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Antibody responses were semi-quantitatively assessed using serum samples analyzed on the Alinity i platform (Abbott Laboratories, Abbott Park, IL) using the FDA-approved SARS-CoV-2 anti-nucleocapsid protein IgG assay (IgGNC), the SARS-CoV-2 anti-spike protein IgM assay (IgMSP), or the SARS-CoV-2 anti-spike protein IgG II assay (IgGSP) as previously described.
    Abbott Laboratories
    suggested: None
    Two-tailed unpaired t-test was performed to assess statistical significance using GraphPad Prism 9.1.0.
    GraphPad Prism
    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:
    Limitations include small sample size, lack of demographic data in non-transplant group, absence of serial measurements after vaccination, and shorter time for follow up. Despite these limitations, we demonstrate that a two-dose format of COVID-19 mRNA vaccines elicit a serological response, though not in a majority of LT patients. Further studies are needed to understand the efficacy and longevity of vaccine-derived COVID-19 immunity in this vulnerable population. Since most lung transplant recipients are maintained at higher level of immunosuppression compared to other solid organ transplant recipients, larger studies with longer duration of follow-up are needed to confirm our preliminary findings of antibody response after completing SARS-CoV-2 mRNA vaccination.

    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.

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

    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 10.1101/2021.04.26.21255926v1 on medRxiv