Antibody prevalence after three or more COVID-19 vaccine doses in individuals who are immunosuppressed in the UK: a cross-sectional study from MELODY
Antibody prevalence after three or more COVID-19 vaccine doses in individuals who are immunosuppressed in the UK: a cross-sectional study from MELODY
Background: In the UK, additional COVID-19 vaccine booster doses and treatments are offered to people who are immunosuppressed to protect against severe COVID-19, but how best to choose the individuals that receive these vaccine booster doses and treatments is unclear. We investigated the association between seropositivity to SARS-CoV-2 spike protein with demographic, disease, and treatment-related characteristics after at least three COVID-19 vaccines in three cohorts of people who are immunosuppressed. Methods: In a cross-sectional study using UK national disease registries, we identified, contacted, and recruited recipients of solid organ transplants, participants with rare autoimmune rheumatic diseases, and participants with lymphoid malignancies who were 18 years or older, resident in the UK, and who had received at least three doses of a COVID-19 vaccine. The study was open to recruitment from Dec 7, 2021, to June 26, 2022. Participants received a lateral flow immunoassay test for SARS-CoV-2 spike antibodies to complete at home, and an online questionnaire. Multivariable logistic regression was used to estimate the mutually adjusted odds of seropositivity against each characteristic. Findings: Between Feb 14 and June 26, 2022, we screened 101 972 people (98 725 invited, 3247 self-enrolled) and recruited 28 411 (27·9%) to the study. 23 036 (81·1%) recruited individuals provided serological data. Of these, 9927 (43·1%) were recipients of solid organ transplants, 6516 (28·3%) had rare autoimmune rheumatic diseases, and 6593 (28·6%) had lymphoid malignancies. 10 485 (45·5%) participants were men and 12 535 (54·4%) were women (gender was not reported for 16 [<0·1%] participants), and 21661 (94·0%) participants were of White ethnicity. The median age of participants with solid organ transplants was 60 years (SD 50–67), with rare autoimmune rheumatic diseases was 65 years (54–73), and with lymphoid malignancy was 69 years (61–75). Of the 23 036 participants with serological data, 6583 (28·6%) had received three vaccine doses, 14 234 (61·8%) had received four vaccine doses, and 2219 (9·6%) had received five or more vaccine doses. IgG anti-spike antibodies were undetectable in 2310 (23·3%) of 9927 patients with solid organ transplants, 922 (14·1%) of 6516 patients with rare autoimmune rheumatic diseases, and 1366 (20·7%) of 6593 patients with lymphoid malignancies. In all groups, seropositivity was associated with younger age, higher number of vaccine doses (ie, five vs three), and previous COVID-19. Immunosuppressive medication reduced the likelihood of seropositivity: the lowest odds of seropositivity were found in recipients of solid organ transplants receiving a combination of an anti-proliferative agent, a calcineurin inhibitor, and steroids, and those with rare autoimmune rheumatic diseases or lymphoid malignancies treated with anti-CD20 therapies. Interpretation: Approximately one in five recipients of solid organ transplants, individuals with rare autoimmune rheumatic diseases, and individuals with lymphoid malignancies have no detectable IgG anti-spike antibodies despite three or more vaccine doses, but this proportion decreases with sequential booster doses. Choice of immunosuppressant and disease type is strongly associated with serological response. Antibody testing using lateral flow immunoassay tests could enable rapid identification of individuals who are most likely to benefit from additional COVID-19 interventions. Funding: UK Research and Innovation, Kidney Research UK, Blood Cancer UK, Vasculitis UK and the Cystic Fibrosis Trust.
e461-e473
Pearce, Fiona A.
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Lim, Sean H.
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Bythell, Mary
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Lanyon, Peter
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Hogg, Rachel
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Taylor, Adam
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Powter, Gillian
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Cooke, Graham S.
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Ward, Helen
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Chilcot, Joseph
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Thomas, Helen
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Mumford, Lisa
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McAdoo, Stephen P.
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Pettigrew, Gavin J.
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Lightstone, Liz
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Willicombe, Michelle
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August 2023
Pearce, Fiona A.
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Lim, Sean H.
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Bythell, Mary
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Lanyon, Peter
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Hogg, Rachel
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Taylor, Adam
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Powter, Gillian
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Cooke, Graham S.
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Ward, Helen
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Chilcot, Joseph
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Thomas, Helen
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Mumford, Lisa
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McAdoo, Stephen P.
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Pettigrew, Gavin J.
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Lightstone, Liz
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Willicombe, Michelle
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Pearce, Fiona A., Lim, Sean H., Bythell, Mary, Lanyon, Peter, Hogg, Rachel, Taylor, Adam, Powter, Gillian, Cooke, Graham S., Ward, Helen, Chilcot, Joseph, Thomas, Helen, Mumford, Lisa, McAdoo, Stephen P., Pettigrew, Gavin J., Lightstone, Liz and Willicombe, Michelle
(2023)
Antibody prevalence after three or more COVID-19 vaccine doses in individuals who are immunosuppressed in the UK: a cross-sectional study from MELODY.
The Lancet Rheumatology, 5 (8), .
(doi:10.1016/S2665-9913(23)00160-1).
Abstract
Background: In the UK, additional COVID-19 vaccine booster doses and treatments are offered to people who are immunosuppressed to protect against severe COVID-19, but how best to choose the individuals that receive these vaccine booster doses and treatments is unclear. We investigated the association between seropositivity to SARS-CoV-2 spike protein with demographic, disease, and treatment-related characteristics after at least three COVID-19 vaccines in three cohorts of people who are immunosuppressed. Methods: In a cross-sectional study using UK national disease registries, we identified, contacted, and recruited recipients of solid organ transplants, participants with rare autoimmune rheumatic diseases, and participants with lymphoid malignancies who were 18 years or older, resident in the UK, and who had received at least three doses of a COVID-19 vaccine. The study was open to recruitment from Dec 7, 2021, to June 26, 2022. Participants received a lateral flow immunoassay test for SARS-CoV-2 spike antibodies to complete at home, and an online questionnaire. Multivariable logistic regression was used to estimate the mutually adjusted odds of seropositivity against each characteristic. Findings: Between Feb 14 and June 26, 2022, we screened 101 972 people (98 725 invited, 3247 self-enrolled) and recruited 28 411 (27·9%) to the study. 23 036 (81·1%) recruited individuals provided serological data. Of these, 9927 (43·1%) were recipients of solid organ transplants, 6516 (28·3%) had rare autoimmune rheumatic diseases, and 6593 (28·6%) had lymphoid malignancies. 10 485 (45·5%) participants were men and 12 535 (54·4%) were women (gender was not reported for 16 [<0·1%] participants), and 21661 (94·0%) participants were of White ethnicity. The median age of participants with solid organ transplants was 60 years (SD 50–67), with rare autoimmune rheumatic diseases was 65 years (54–73), and with lymphoid malignancy was 69 years (61–75). Of the 23 036 participants with serological data, 6583 (28·6%) had received three vaccine doses, 14 234 (61·8%) had received four vaccine doses, and 2219 (9·6%) had received five or more vaccine doses. IgG anti-spike antibodies were undetectable in 2310 (23·3%) of 9927 patients with solid organ transplants, 922 (14·1%) of 6516 patients with rare autoimmune rheumatic diseases, and 1366 (20·7%) of 6593 patients with lymphoid malignancies. In all groups, seropositivity was associated with younger age, higher number of vaccine doses (ie, five vs three), and previous COVID-19. Immunosuppressive medication reduced the likelihood of seropositivity: the lowest odds of seropositivity were found in recipients of solid organ transplants receiving a combination of an anti-proliferative agent, a calcineurin inhibitor, and steroids, and those with rare autoimmune rheumatic diseases or lymphoid malignancies treated with anti-CD20 therapies. Interpretation: Approximately one in five recipients of solid organ transplants, individuals with rare autoimmune rheumatic diseases, and individuals with lymphoid malignancies have no detectable IgG anti-spike antibodies despite three or more vaccine doses, but this proportion decreases with sequential booster doses. Choice of immunosuppressant and disease type is strongly associated with serological response. Antibody testing using lateral flow immunoassay tests could enable rapid identification of individuals who are most likely to benefit from additional COVID-19 interventions. Funding: UK Research and Innovation, Kidney Research UK, Blood Cancer UK, Vasculitis UK and the Cystic Fibrosis Trust.
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e-pub ahead of print date: 24 July 2023
Published date: August 2023
Additional Information:
Funding Information:
This study was funded by UK Research and Innovation (Medical Research Council; MR/W029200/1), Kidney Research UK, Blood Cancer UK, Vasculitis UK, and the Cystic Fibrosis Trust. This work uses data that have been provided by patients, the NHS, and other health-care organisations as part of routine patient care and support. The cancer and rare disease data are collated, maintained, and quality assured by the National Disease Registration Service, which are part of NHS England. The authors are grateful to all the transplant centres in the UK who contributed data on which the solid organ transplant analysis is based. Support for this work was also provided by Jeanette Aston and Peter Stilwell at the NDRS, and David Groves from the University of Nottingham. The authors would like to thank the patients who helped develop the study design. MW and SPMc are supported by the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) based at Imperial College Healthcare NHS Trust and Imperial College London. SHL is supported by a Cancer Research UK Advanced Clinician Scientist Fellowship (A27179). HW is a National Institute for Health Research (NIHR) Senior Investigator and acknowledges support from the Imperial NIHR BRC, NIHR School of Public Health Research, and the NIHR Applied Research Collaborative Northwest London. GSC acknowledges support from the Imperial NIHR BRC and the Department of Health and Social Care. GJP is supported by the NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation at Cambridge, jointly partnered by Cambridge and Newcastle Universities. FAP is funded by the National Institute for Health Research (NIHR Advanced Fellow NIHR300863). The views expressed in this publication are those of the authors and not necessarily those of the NIHR, NHS, or the UK Department of Health and Social Care.
Funding Information:
This study was funded by UK Research and Innovation (Medical Research Council; MR/W029200/1), Kidney Research UK, Blood Cancer UK, Vasculitis UK, and the Cystic Fibrosis Trust. This work uses data that have been provided by patients, the NHS, and other health-care organisations as part of routine patient care and support. The cancer and rare disease data are collated, maintained, and quality assured by the National Disease Registration Service, which are part of NHS England. The authors are grateful to all the transplant centres in the UK who contributed data on which the solid organ transplant analysis is based. Support for this work was also provided by Jeanette Aston and Peter Stilwell at the NDRS, and David Groves from the University of Nottingham. The authors would like to thank the patients who helped develop the study design. MW and SPMc are supported by the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) based at Imperial College Healthcare NHS Trust and Imperial College London. SHL is supported by a Cancer Research UK Advanced Clinician Scientist Fellowship (A27179). HW is a National Institute for Health Research (NIHR) Senior Investigator and acknowledges support from the Imperial NIHR BRC, NIHR School of Public Health Research, and the NIHR Applied Research Collaborative Northwest London. GSC acknowledges support from the Imperial NIHR BRC and the Department of Health and Social Care. GJP is supported by the NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation at Cambridge, jointly partnered by Cambridge and Newcastle Universities. FAP is funded by the National Institute for Health Research (NIHR Advanced Fellow NIHR300863). The views expressed in this publication are those of the authors and not necessarily those of the NIHR, NHS, or the UK Department of Health and Social Care.
Publisher Copyright:
© 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license
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Local EPrints ID: 480538
URI: http://eprints.soton.ac.uk/id/eprint/480538
ISSN: 2665-9913
PURE UUID: 57f8cc3f-b8f6-479b-a04a-1a72d25b63b0
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Date deposited: 04 Aug 2023 16:36
Last modified: 17 Mar 2024 03:51
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Author:
Fiona A. Pearce
Author:
Mary Bythell
Author:
Peter Lanyon
Author:
Rachel Hogg
Author:
Adam Taylor
Author:
Gillian Powter
Author:
Graham S. Cooke
Author:
Helen Ward
Author:
Joseph Chilcot
Author:
Helen Thomas
Author:
Lisa Mumford
Author:
Stephen P. McAdoo
Author:
Gavin J. Pettigrew
Author:
Liz Lightstone
Author:
Michelle Willicombe
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