Skip to main content

Main menu

  • Home
  • Our journals
    • Clinical Medicine
    • Future Healthcare Journal
  • Subject collections
  • About the RCP
  • Contact us

Future Healthcare Journal

  • FHJ Home
  • Content
    • Current
    • Ahead of print
    • Archive
  • Author guidance
    • Instructions for authors
    • Submit online
  • About FHJ
    • Scope
    • Editorial board
    • Policies
    • Information for reviewers
    • Advertising

User menu

  • Log in

Search

  • Advanced search
RCP Journals
Home
  • Log in
  • Home
  • Our journals
    • Clinical Medicine
    • Future Healthcare Journal
  • Subject collections
  • About the RCP
  • Contact us
Advanced

Future Healthcare Journal

futurehosp Logo
  • FHJ Home
  • Content
    • Current
    • Ahead of print
    • Archive
  • Author guidance
    • Instructions for authors
    • Submit online
  • About FHJ
    • Scope
    • Editorial board
    • Policies
    • Information for reviewers
    • Advertising

Failure to mount a humoral response to COVID-19 vaccination identifies individuals with previously undiagnosed severe antibody deficiency state: preliminary data from the COVID-19 ENLIST study

Mark Ponsford
Download PDF
DOI: https://doi.org/10.7861/fhj.9-2-s25
Future Healthc J July 2022
Mark Ponsford
ACardiff University, Cardiff, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
Loading

Introduction

Immunisation with mRNA or adenovirus-based COVID-19 vaccinations provides a potent immunogenic stimulus. In the vast majority of individuals, vaccination elicits cellular and humoral (antibody) immune responses to the spike protein mediating protection against severe disease against SARS-CoV-2 infection, including novel variants.1 However, susceptibility to severe disease and failure to respond to COVID-19 vaccinations remain a particular concern in immunocompromised patient groups.2 In a recent survey of vaccine responses in individuals with inherited and acquired forms of immunodeficiency, the magnitude of the humoral IgG vaccine response to COVID-19 vaccines appeared related to the magnitude and nature of the underlying immunodeficiency.2 Here, I explore the novel concept that failure to elicit a humoral vaccine response can identify individuals with previously undiagnosed humoral immunodeficiency, in a pilot study of solid-organ transplant recipients (SOTRs).3

Material and methods

Serum was obtained from participants enrolled in the COVID-19 ENLIST vaccination sub-study (REC reference: 20/YH/0309). Samples were obtained following informed consent and at least 14-days following receipt of two doses of COVID-19 vaccination, as recently described.3 Anti-SARS-CoV-2 spike S1 IgG serological responses were determined using a commercial assay (EUROIMMUN) as per kit instructions. Total IgG, IgA, and IgM levels were analysed using the Optilite® turbidimeter in consecutive stored sera with anti-SARS-CoV-2 spike IgG levels above (‘responders’, n=15) and below (‘non-responders’, n=18) the assay's limit of detection for a positive anti-spike IgG response. Comparisons are presented by vaccine response group and relative to the UK laboratory adult reference range (approximately normally distributed). Data were curated in Microsoft Excel with statistical analysis in GraphPad Prism v6.0. Severe hypogammaglobulinaemia was defined as a serum IgG <4 g/L, based on meta-analysis demonstrating a doubling in the risk of infections below this level.4

Results and discussion

The percentage of SOTRs with serum immunoglobulin class below the lower limit of normal is shown in Table 1. Individuals failing to mount a detectable anti-spike IgG response following COVID-19 vaccination display a substantially increased frequency of low IgG and low IgM levels, compared with the UK reference population (Fisher's exact test: p=0.0093 and p<0.0001, respectively). While there was no statistically significant difference in the odds of a low IgG (<6 g/L) between the SOTR vaccine responder/non-responder groups (Fisher's exact test: p=0.340), the lowest IgG in the vaccine non-responder group was 3.1 g/L is clinically relevant.

View this table:
  • View inline
  • View popup
Table 1.

Percentage of solid organ transplant recipients with serum immunoglobulin class below the lower limit of normal

Conclusion

Antibody deficiency is a treatable cause of infection susceptibility;5 however, recognition is reliant on laboratory diagnosis. Solidorgan transplant recipients are at increased risk of hypogammaglobulinaemia due to factors including the use of anti-rejection immunosuppressive medications, but severe deficiency remains rare.6 This preliminary data support the hypothesis that failure to produce a detectable anti-SARS-CoV-2 spike IgG response following at least two COVID-19 vaccine doses is associated with a reduction in the serum levels of IgG. Remarkably, this pilot study identified an individual with an IgG level of 3.1 g/L, consistent with severe IgG deficiency and directs clinical assessment with potential consideration of immunoglobulin replacement therapy.

Funding statement

Welsh Clinical Academic Training (WCAT) Fellowship; Kidney Wales; Association of Clinical Pathologists.

  • © Royal College of Physicians 2022. All rights reserved.

References

  1. ↵
    1. Gao Y
    , Cai C, Grifoni A, Müller TR, et al. Ancestral SARS-CoV-2-specific T cells cross-recognize the Omicron variant. Nature Med 2022, in press (DOI: 10.1038/s41591-022-01700-x).
  2. ↵
    1. Ponsford MJ
    , Evans K, Carne E, Jolles S. COVID-19 vaccine uptake and efficacy in a national immunodeficiency cohort. J Clin Immunol 2022, in press (DOI: 10.1007/s10875-022-01223-7).
  3. ↵
    1. Asderakis A
    , Khalid U, Koimtzis G, et al. An analysis of serological response and infection outcomes following Oxford Astra Zeneca (AZD1222) and Pfizer-BioNTech (mRNA BNT162b2) SARS-CoV-2 vaccines in kidney and kidney-pancreas transplants. Transplantation 2022, in press (DOI: 10.1097/TP.0000000000004105).
  4. ↵
    1. Florescu DF
    , Kalil AC, Qiu F, Schmidt CM, Sandkovsky U. What is the impact of hypogammaglobulinemia on the rate of infections and survival in solid organ transplantation? A meta-analysis. Am J Transplant 2013;13:2601–10.
    OpenUrlCrossRefPubMed
  5. ↵
    1. Ponsford M
    , Carne E, Kingdon C, et al. Facilitated subcutaneous immunoglobulin (fSCIg) therapy – practical considerations. Clin Exp Immunol 2015;182:302–13.
    OpenUrl
  6. ↵
    1. Sarmiento E
    , Jimenez M, di Natale M, Rodriguez-Ferrero M, Anaya F, Lopez-Hoyos M, et al. Secondary antibody deficiency is associated with development of infection in kidney transplantation: Results of a multicenter study. Transpl Infect Dis 2021;23:e13494.
    OpenUrl
Back to top
Previous articleNext article

Article Tools

Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Citation Tools
Failure to mount a humoral response to COVID-19 vaccination identifies individuals with previously undiagnosed severe antibody deficiency state: preliminary data from the COVID-19 ENLIST study
Mark Ponsford
Future Healthc J Jul 2022, 9 (Suppl 2) 25-26; DOI: 10.7861/fhj.9-2-s25

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Failure to mount a humoral response to COVID-19 vaccination identifies individuals with previously undiagnosed severe antibody deficiency state: preliminary data from the COVID-19 ENLIST study
Mark Ponsford
Future Healthc J Jul 2022, 9 (Suppl 2) 25-26; DOI: 10.7861/fhj.9-2-s25
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Introduction
    • Material and methods
    • Results and discussion
    • Conclusion
    • Funding statement
    • References
  • Figures & Data
  • Info & Metrics

Related Articles

  • No related articles found.
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • Dignity at work in the NHS
  • Palliative care virtual ward: early evaluation of a novel model of care to support patients with complex symptom management known to a UK tertiary hospital specialist palliative care team
Show more Research and innovation

Similar Articles

FAQs

  • Difficulty logging in.

There is currently no login required to access the journals. Please go to the home page and simply click on the edition that you wish to read. If you are still unable to access the content you require, please let us know through the 'Contact us' page.

  • Can't find the CME questionnaire.

The read-only self-assessment questionnaire (SAQ) can be found after the CME section in each edition of Clinical Medicine. RCP members and fellows (using their login details for the main RCP website) are able to access the full SAQ with answers and are awarded 2 CPD points upon successful (8/10) completion from:  https://cme.rcplondon.ac.uk

Navigate this Journal

  • Journal Home
  • Current Issue
  • Ahead of Print
  • Archive

Related Links

  • ClinMed - Home
  • FHJ - Home

Other Services

  • Advertising
futurehosp Footer Logo
  • Home
  • Journals
  • Contact us
  • Advertise
HighWire Press, Inc.

Follow Us:

  • Follow HighWire Origins on Twitter
  • Visit HighWire Origins on Facebook

Copyright © 2021 by the Royal College of Physicians