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Humoral and cellular immune responses on SARS-CoV-2 vaccines in patients with anti-CD20 therapies: a systematic review and meta-analysis of 1342 patients

BACKGROUND: Immune responses on SARS-CoV-2 vaccination in patients receiving anti-CD20 therapies are impaired but vary considerably. We conducted a systematic review and meta-analysis of the literature on SARS-CoV-2 vaccine induced humoral and cell-mediated immune response in patients previously tre...

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Autores principales: Schietzel, Simeon, Anderegg, Manuel, Limacher, Andreas, Born, Alexander, Horn, Michael P, Maurer, Britta, Hirzel, Cedric, Sidler, Daniel, Moor, Matthias B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8814433/
https://www.ncbi.nlm.nih.gov/pubmed/35115385
http://dx.doi.org/10.1136/rmdopen-2021-002036
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author Schietzel, Simeon
Anderegg, Manuel
Limacher, Andreas
Born, Alexander
Horn, Michael P
Maurer, Britta
Hirzel, Cedric
Sidler, Daniel
Moor, Matthias B
author_facet Schietzel, Simeon
Anderegg, Manuel
Limacher, Andreas
Born, Alexander
Horn, Michael P
Maurer, Britta
Hirzel, Cedric
Sidler, Daniel
Moor, Matthias B
author_sort Schietzel, Simeon
collection PubMed
description BACKGROUND: Immune responses on SARS-CoV-2 vaccination in patients receiving anti-CD20 therapies are impaired but vary considerably. We conducted a systematic review and meta-analysis of the literature on SARS-CoV-2 vaccine induced humoral and cell-mediated immune response in patients previously treated with anti-CD20 antibodies. METHODS: We searched PubMed, Embase, Medrxiv and SSRN using variations of search terms ‘anti-CD20’, ‘vaccine’ and ‘COVID’ and included original studies up to 21 August 2021. We excluded studies with missing data on humoral or cell-mediated immune response, unspecified methodology of response testing, unspecified timeframes between vaccination and blood sampling or low number of participants (≤3). We excluded individual patients with prior COVID-19 or incomplete vaccine courses. Primary endpoints were humoral and cell-mediated immune response rates. Subgroup analyses included time since anti-CD20 therapy, B cell depletion and indication for anti-CD20 therapy. We used random-effects models of proportions. FINDINGS: Ninety studies were assessed. Inclusion criteria were met by 23 studies comprising 1342 patients. Overall rate of humoral response was 0.40 (95% CI 0.35 to 0.47). Overall rate of cell-mediated immune responses was 0.71 (95% CI 0.57 to 0.87). A time interval >6 months since last anti-CD20 therapy was associated with higher humoral response rates with 0.63 (95% CI 0.53 to 0.72) versus <6 months 0.2 (95% CI 0.03 to 0.43); p=0<01. Similarly, patients with circulating B cells more frequently showed humoral responses. Anti-CD20-treated kidney transplant recipients showed lower humoral response rates than patients with haematological malignancies or autoimmune disease. INTERPRETATION: Patients on anti-CD20 therapies can develop humoral and cell-mediated immune responses after SARS-CoV-2 vaccination, but subgroups such as kidney transplant recipients or those with very recent therapy and depleted B cell are at high risk for non-seroconversion and should be individually assessed for personalised SARS-CoV-2 vaccination strategies. Potential limitations are small patient numbers and heterogeneity of studies included. FUNDING: This study was funded by Bern University Hospital.
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spelling pubmed-88144332022-02-04 Humoral and cellular immune responses on SARS-CoV-2 vaccines in patients with anti-CD20 therapies: a systematic review and meta-analysis of 1342 patients Schietzel, Simeon Anderegg, Manuel Limacher, Andreas Born, Alexander Horn, Michael P Maurer, Britta Hirzel, Cedric Sidler, Daniel Moor, Matthias B RMD Open Infections BACKGROUND: Immune responses on SARS-CoV-2 vaccination in patients receiving anti-CD20 therapies are impaired but vary considerably. We conducted a systematic review and meta-analysis of the literature on SARS-CoV-2 vaccine induced humoral and cell-mediated immune response in patients previously treated with anti-CD20 antibodies. METHODS: We searched PubMed, Embase, Medrxiv and SSRN using variations of search terms ‘anti-CD20’, ‘vaccine’ and ‘COVID’ and included original studies up to 21 August 2021. We excluded studies with missing data on humoral or cell-mediated immune response, unspecified methodology of response testing, unspecified timeframes between vaccination and blood sampling or low number of participants (≤3). We excluded individual patients with prior COVID-19 or incomplete vaccine courses. Primary endpoints were humoral and cell-mediated immune response rates. Subgroup analyses included time since anti-CD20 therapy, B cell depletion and indication for anti-CD20 therapy. We used random-effects models of proportions. FINDINGS: Ninety studies were assessed. Inclusion criteria were met by 23 studies comprising 1342 patients. Overall rate of humoral response was 0.40 (95% CI 0.35 to 0.47). Overall rate of cell-mediated immune responses was 0.71 (95% CI 0.57 to 0.87). A time interval >6 months since last anti-CD20 therapy was associated with higher humoral response rates with 0.63 (95% CI 0.53 to 0.72) versus <6 months 0.2 (95% CI 0.03 to 0.43); p=0<01. Similarly, patients with circulating B cells more frequently showed humoral responses. Anti-CD20-treated kidney transplant recipients showed lower humoral response rates than patients with haematological malignancies or autoimmune disease. INTERPRETATION: Patients on anti-CD20 therapies can develop humoral and cell-mediated immune responses after SARS-CoV-2 vaccination, but subgroups such as kidney transplant recipients or those with very recent therapy and depleted B cell are at high risk for non-seroconversion and should be individually assessed for personalised SARS-CoV-2 vaccination strategies. Potential limitations are small patient numbers and heterogeneity of studies included. FUNDING: This study was funded by Bern University Hospital. BMJ Publishing Group 2022-02-03 /pmc/articles/PMC8814433/ /pubmed/35115385 http://dx.doi.org/10.1136/rmdopen-2021-002036 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Infections
Schietzel, Simeon
Anderegg, Manuel
Limacher, Andreas
Born, Alexander
Horn, Michael P
Maurer, Britta
Hirzel, Cedric
Sidler, Daniel
Moor, Matthias B
Humoral and cellular immune responses on SARS-CoV-2 vaccines in patients with anti-CD20 therapies: a systematic review and meta-analysis of 1342 patients
title Humoral and cellular immune responses on SARS-CoV-2 vaccines in patients with anti-CD20 therapies: a systematic review and meta-analysis of 1342 patients
title_full Humoral and cellular immune responses on SARS-CoV-2 vaccines in patients with anti-CD20 therapies: a systematic review and meta-analysis of 1342 patients
title_fullStr Humoral and cellular immune responses on SARS-CoV-2 vaccines in patients with anti-CD20 therapies: a systematic review and meta-analysis of 1342 patients
title_full_unstemmed Humoral and cellular immune responses on SARS-CoV-2 vaccines in patients with anti-CD20 therapies: a systematic review and meta-analysis of 1342 patients
title_short Humoral and cellular immune responses on SARS-CoV-2 vaccines in patients with anti-CD20 therapies: a systematic review and meta-analysis of 1342 patients
title_sort humoral and cellular immune responses on sars-cov-2 vaccines in patients with anti-cd20 therapies: a systematic review and meta-analysis of 1342 patients
topic Infections
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8814433/
https://www.ncbi.nlm.nih.gov/pubmed/35115385
http://dx.doi.org/10.1136/rmdopen-2021-002036
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