Antibody Responses to SARS-CoV-2 After Infection or Vaccination in Children and Young Adults With Inflammatory Bowel Disease

  1. Joelynn Dailey
  2. Lina Kozhaya
  3. Mikail Dogan
  4. Dena Hopkins
  5. Blaine Lapin
  6. Katherine Herbst
  7. Michael Brimacombe
  8. Kristen Grandonico
  9. Fatih Karabacak
  10. John Schreiber
  11. Bruce Tsan-Liang Liang
  12. Juan C Salazar
  13. Derya Unutmaz
  14. Jeffrey S Hyams

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Abstract

Background

Characterization of neutralization antibodies to SARS-CoV-2 infection or vaccination in children and young adults with inflammatory bowel disease (IBD) receiving biologic therapies is crucial.

Methods

We performed a prospective longitudinal cohort study evaluating SARS-CoV-2 spike protein receptor binding domain (S-RBD) IgG positivity along with consistent clinical symptoms in patients with IBD receiving infliximab or vedolizumab. Serum was also obtained following immunization with approved vaccines. The IgG antibody to the spike protein binding domain of SARS-CoV-2 was assayed with a fluorescent bead-based immunoassay that takes advantage of the high dynamic range of fluorescent molecules using flow cytometry. A sensitive and high-throughput neutralization assay that incorporates SARS-CoV-2 spike protein onto a lentivirus and measures pseudoviral entry into ACE2-angiotensin converting enzyme 2 (ACE2) expressing human embryonic kidney 293 (HEK-293) cells was used.

Results

There were 436 patients enrolled (mean age, 17 years, range 2–26 years; 58% male; 71% Crohn’s disease, 29% ulcerative colitis, IBD-unspecified). Forty-four (10%) of enrolled subjects had SARS-CoV-2 S-RBD IgG antibodies. Compared to non-IBD adults (ambulatory) and hospitalized pediatric patients with PCR documented SARS-CoV-2 infection, S-RBD IgG antibody levels were significantly lower in the IBD cohort and by 6 months post infection most patients lacked neutralizing antibody. Following vaccination (n = 33), patients had a 15-fold higher S-RBD antibody response in comparison with natural infection, and all developed neutralizing antibodies to both wild type and variant SARS-CoV-2.

Conclusions

The lower and less durable SARS-CoV-2 S-RBD IgG response to natural infection in IBD patients receiving biologics puts them at risk of reinfection. The robust response to immunization is likely protective.

Article activity feed

  1. Version published to 10.1093/ibd/izab207
  2. ScreenIT

    SciScore for 10.1101/2021.06.12.21258810: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: This study was reviewed by the Institutional Review Board at Connecticut Children’s and deemed minimal risk.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    SARS-CoV-2 Spike protein binding domain (S-RBD) IgG antibody responses: To measure SARS-CoV-2 S-RBD IgG antibodies we used a fluorescent bead-based immunoassay developed as previously described (15).
    SARS-CoV-2 Spike protein binding domain (S-RBD) IgG
    suggested: None
    S-RBD IgG
    suggested: None
    We screened patient serum samples for SARS-CoV-2 wild type (WT) S-RBD or K417N, E484K, N501 mutant (mt S-RBD) Spike protein receptor binding domain specific IgG antibodies.
    Spike protein receptor binding domain specific IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Data were entered into a Research Electronic Data Capture (REDCap) system (14).
    REDCap
    suggested: (REDCap, RRID:SCR_003445)
    Serum from adults without IBD (UConn Healthcare workers, n=23) with SARS-CoV-2 infection who remained ambulatory were collected at the time of diagnosis (baseline) and 2, 4, 6 months.
    UConn Healthcare
    suggested: None
    Flow cytometry data were analyzed using FlowJo (BD biosciences)
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Statistical analyses were performed using GraphPad Prism 8.0 software (GraphPad Software)
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    NT50 was determined using 4-parameter nonlinear regression (GraphPad Prism 8.0).
    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:
    There were also several limitations. We did not have control data from IBD patients not receiving biologics, particularly those on methotrexate or thiopurine monotherapy. We also do not yet have longitudinal data on the durability of antibody response following vaccination. Finally, we did not test antibody neutralization ability from our patients against emerging SARS CoV-2 variants which may reveal lower titers and a more rapid decline in protective levels. However, given almost perfect correlation of S-RBD IgG levels with the NT50 (Supplemental Figure 1b) and a 34.3x lower antibody response to mutant S-RBD in natural infection compared to vaccine (Figure 4c), we anticipate neutralization activity to decline as we observed for the S-RBD antibody level. In conclusion, the humoral response to SARS-CoV-2 infection in children and young adults was less than in adult and pediatric non-IBD controls and neutralizing antibody was absent in most infected IBD patients by 6 months. The robust response to immunization was reassuring and supports the utility of vaccinating these patients. Further data will be required to understand the durability of the response to the vaccine, whether previous infection will enhance the antibody response to the vaccine in this patient group lessening the need for a second dose, and whether chronic anti-metabolite administration will have a mitigating influence over time.

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

    IdentifierStatusTitle
    NCT04838834Active, not recruitingMonitoring Serologic Response to Severe Acute Respiratory Sy…

    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.

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  3. Version published to 10.1101/2021.06.12.21258810 on medRxiv