Prospective Evaluation of Coronavirus Disease 2019 (COVID-19) Vaccine Responses Across a Broad Spectrum of Immunocompromising Conditions: the COVID-19 Vaccination in the Immunocompromised Study (COVICS)

  1. Ghady Haidar
  2. Mounzer Agha
  3. Andrew Bilderback
  4. Amy Lukanski
  5. Kelsey Linstrum
  6. Rachel Troyan
  7. Scott Rothenberger
  8. Deborah K McMahon
  9. Melissa D Crandall
  10. Michele D Sobolewksi
  11. P Nathan Enick
  12. Jana L Jacobs
  13. Kevin Collins
  14. Cynthia Klamar-Blain
  15. Bernard J C Macatangay
  16. Urvi M Parikh
  17. Amy Heaps
  18. Lindsay Coughenour
  19. Marc B Schwartz
  20. Jeffrey M Dueker
  21. Fernanda P Silveira
  22. Mary E Keebler
  23. Abhinav Humar
  24. James D Luketich
  25. Matthew R Morrell
  26. Joseph M Pilewski
  27. John F McDyer
  28. Bhanu Pappu
  29. Robert L Ferris
  30. Stanley M Marks
  31. John Mahon
  32. Katie Mulvey
  33. Sundaram Hariharan
  34. Glenn M Updike
  35. Lorraine Brock
  36. Robert Edwards
  37. Richard H Beigi
  38. Paula L Kip
  39. Alan Wells
  40. Tami Minnier
  41. Derek C Angus
  42. John W Mellors

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Background

We studied humoral responses after coronavirus disease 2019 (COVID-19) vaccination across varying causes of immunodeficiency.

Methods

Prospective study of fully vaccinated immunocompromised adults (solid organ transplant [SOT], hematologic malignancy, solid cancers, autoimmune conditions, human immunodeficiency virus [HIV]) versus nonimmunocompromised healthcare workers (HCWs). The primary outcome was the proportion with a reactive test (seropositive) for immunoglobulin G to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain. Secondary outcomes were comparisons of antibody levels and their correlation with pseudovirus neutralization titers. Stepwise logistic regression was used to identify factors associated with seropositivity.

Results

A total of 1271 participants enrolled: 1099 immunocompromised and 172 HCW. Compared with HCW (92.4% seropositive), seropositivity was lower among participants with SOT (30.7%), hematological malignancies (50.0%), autoimmune conditions (79.1%), solid tumors (78.7%), and HIV (79.8%) (P < .01). Factors associated with poor seropositivity included age, greater immunosuppression, time since vaccination, anti-CD20 monoclonal antibodies, and vaccination with BNT162b2 (Pfizer) or adenovirus vector vaccines versus messenger RNA (mRNA)-1273 (Moderna). mRNA-1273 was associated with higher antibody levels than BNT162b2 or adenovirus vector vaccines after adjusting for time since vaccination, age, and underlying condition. Antibody levels were strongly correlated with pseudovirus neutralization titers (Spearman r = 0.89, P < .0001), but in seropositive participants with intermediate antibody levels, neutralization titers were significantly lower in immunocompromised individuals versus HCW.

Conclusions

Antibody responses to COVID-19 vaccines were lowest among SOT and anti-CD20 monoclonal recipients, and recipients of vaccines other than mRNA-1273. Among those with intermediate antibody levels, pseudovirus neutralization titers were lower in immunocompromised patients than HCWs. Additional SARS-CoV-2 preventive approaches are needed for immunocompromised persons, which may need to be tailored to the cause of immunodeficiency.

Article activity feed

  1. Version published to 10.1093/cid/ciac103
  2. ScreenIT

    SciScore for 10.1101/2021.06.28.21259576: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The study was approved by the University of Pittsburgh Institutional Review Board (Study ID: 21030056/HCC 21-032).
    Field Sample Permit: Data Collection and Outcomes: Study data were collected by the project coordinators and managed using the Research Electronic Data Capture (REDCap) hosted at the University of Pittsburgh.10 REDCap is a secure, web-based software platform designed to support data capture for research studies.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Antibody assays: Serum underwent antibody testing using the Beckman Coulter SARS-CoV-2 platform (Spike (S) receptor-binding domain (RBD) IgG).
    Spike (S) receptor-binding domain (RBD) IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    SARS-CoV-2 pseudovirus (PSV) was generated in 293T cells by co-transfection of pFC37K-CMV-S, an enhanced expression plasmid encoding for codon-optimized full-length SARS-CoV-2 S (Wuhan-1 sequence containing D614G substitution) with the N-term HiBit tag removed, and pNL4-3.luc.R-E-mCherry-luciferase, an envelope deficient HIV-1 dual reporter construct that was cloned by recombination of the pNL.luc.R-E-plasmid (NIH AIDS Reagent Program) and the fully infectious pNL4-3 mCherry luciferase plasmid (Addgene).
    293T
    suggested: None
    For neutralization assays, 104 293T-hACE2 cells were plated in 100 microliters (μL) media per well in 96 well white-wall white-bottom plates (Perkin Elmer) and incubated overnight at 37°C.
    293T-hACE2
    suggested: None
    Recombinant DNA
    SentencesResources
    SARS-CoV-2 pseudovirus (PSV) was generated in 293T cells by co-transfection of pFC37K-CMV-S, an enhanced expression plasmid encoding for codon-optimized full-length SARS-CoV-2 S (Wuhan-1 sequence containing D614G substitution) with the N-term HiBit tag removed, and pNL4-3.luc.R-E-mCherry-luciferase, an envelope deficient HIV-1 dual reporter construct that was cloned by recombination of the pNL.luc.R-E-plasmid (NIH AIDS Reagent Program) and the fully infectious pNL4-3 mCherry luciferase plasmid (Addgene).
    pFC37K-CMV-S
    suggested: None
    pNL4-3.luc.R-E-mCherry-luciferase
    suggested: None
    pNL.luc.R-E-plasmid
    suggested: None
    pNL4-3 mCherry luciferase
    suggested: None
    Software and Algorithms
    SentencesResources
    Data Collection and Outcomes: Study data were collected by the project coordinators and managed using the Research Electronic Data Capture (REDCap) hosted at the University of Pittsburgh.10 REDCap is a secure, web-based software platform designed to support data capture for research studies.
    REDCap
    suggested: (REDCap, RRID:SCR_003445)

    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 of this study include lack of longitudinal sampling and assessment of cellular immunity. Nonetheless, our data call for the need for funding to better understand immune responses to COVID-19 vaccines in immunosuppressed patients. Future studies should focus on correlating immune responses with clinical efficacy of COVID-19 vaccines and measurement of other correlates of immunity such as T-cell and memory B-cell responses, particularly in seronegative patients. There is a critical need to develop studies of revaccination, and for countries providing revaccination to publish their data. There is also a critical need to design trials of passive immunity using monoclonal antibodies or direct-acting antivirals for the prevention of COVID-19 in immunocompromised patients. Finally, results such as ours should not be used to fuel vaccine hesitancy, but rather to encourage vaccination and emphasize the need for ongoing vigilance until additional interventions are available.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04885907Active, not recruitingThird Dose of Moderna COVID-19 Vaccine in Transplant Recipie…

    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

    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 10.1101/2021.06.28.21259576v1 on medRxiv