Antibody, cell-mediated response and infection susceptibility in allogeneic hematopoietic stem cell recipients after COVID-19 mRNA vaccination.


Journal

Transplant infectious disease : an official journal of the Transplantation Society
ISSN: 1399-3062
Titre abrégé: Transpl Infect Dis
Pays: Denmark
ID NLM: 100883688

Informations de publication

Date de publication:
Apr 2023
Historique:
revised: 01 11 2022
received: 14 09 2022
accepted: 16 11 2022
medline: 11 4 2023
pubmed: 8 2 2023
entrez: 7 2 2023
Statut: ppublish

Résumé

Patients undergoing allogeneic stem-cell transplantation (allo-SCT) have reduced responses to vaccines due to immunosuppressive status linked to GvHD prophylaxis and treatment. In our study, we compared humoral responses to anti-SARS-CoV-2 mRNA vaccine, and infection onset, according to patients and transplant features; we also evaluated cellular response in patients without seroconversion. We tested antibodies titer after second and third vaccine doses. Antibodies were detected through an immune-enzymatic assay. In a patients' subgroup without seroconversion, we tested cell-mediated responses evaluating interferon-gamma release by T-lymphocytes exposed to virus spike protein. Seroconversion rate increased from 66% at 30 days to 81% at 90 days after the second dose; it was 97% at 150 days after the third dose. We found a significant association between seroconversion after the second dose and two variables: shorter interval between allo-SCT and vaccination; ongoing immunosuppression. Twelve of 19 patients (63%) without antibodies after the second dose did not show cellular responses. Nineteen percent of patients developed SARS-CoV-2 infection after the third dose, with favorable outcome in all cases. Patients within 12 months after allo-SCT showed a significantly higher infection risk. Our study suggests that an interval shorter than 12 months between allo-SCT and first vaccine dose and/or ongoing immunosuppression were associated with humoral and cellular response deficiency after two doses. Third dose induced an increased and sustained humoral response in the majority of patients. However, patients within 1 year after allo-SCT remained at higher infection risk and may be candidate for prophylaxis with anti-SARS-CoV-2 monoclonal antibodies.

Sections du résumé

BACKGROUND BACKGROUND
Patients undergoing allogeneic stem-cell transplantation (allo-SCT) have reduced responses to vaccines due to immunosuppressive status linked to GvHD prophylaxis and treatment. In our study, we compared humoral responses to anti-SARS-CoV-2 mRNA vaccine, and infection onset, according to patients and transplant features; we also evaluated cellular response in patients without seroconversion.
METHODS METHODS
We tested antibodies titer after second and third vaccine doses. Antibodies were detected through an immune-enzymatic assay. In a patients' subgroup without seroconversion, we tested cell-mediated responses evaluating interferon-gamma release by T-lymphocytes exposed to virus spike protein.
RESULTS RESULTS
Seroconversion rate increased from 66% at 30 days to 81% at 90 days after the second dose; it was 97% at 150 days after the third dose. We found a significant association between seroconversion after the second dose and two variables: shorter interval between allo-SCT and vaccination; ongoing immunosuppression. Twelve of 19 patients (63%) without antibodies after the second dose did not show cellular responses. Nineteen percent of patients developed SARS-CoV-2 infection after the third dose, with favorable outcome in all cases. Patients within 12 months after allo-SCT showed a significantly higher infection risk.
CONCLUSIONS CONCLUSIONS
Our study suggests that an interval shorter than 12 months between allo-SCT and first vaccine dose and/or ongoing immunosuppression were associated with humoral and cellular response deficiency after two doses. Third dose induced an increased and sustained humoral response in the majority of patients. However, patients within 1 year after allo-SCT remained at higher infection risk and may be candidate for prophylaxis with anti-SARS-CoV-2 monoclonal antibodies.

Identifiants

pubmed: 36748718
doi: 10.1111/tid.14003
doi:

Substances chimiques

Antibodies, Viral 0
RNA, Messenger 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e14003

Informations de copyright

© 2023 Wiley Periodicals LLC.

Références

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Passamonti F, Cattaneo C, Arcaini L, et al. ITA-HEMA-COV Investigators. Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study. Lancet Haematol. 2020;7(10):e737-e745.
Palanques-Pastor T, Megías-Vericat JE, Martínez P, et al. Characteristics, clinical outcomes, and risk factors of SARS-COV-2 infection in adult acute myeloid leukemia patients: experience of the PETHEMA group. Leuk Lymphoma. 2021;62(12):2928-2938.
Negahdaripour M, Shafiekhani M, Moezzi SMI, et al. Administration of COVID-19 vaccines in immunocompromised patients. Int Immunopharmacol. 2021;99:108021.
Sharma A, Bhatt N, St Martin A et al., Clinical characteristics and outcomes of COVID-19 in haematopoietic stem-cell transplantation recipients: an observational cohort study. Lancet Haematol. 2021;8(3):e185-e193.
Clémenceau B, Guillaume T, Coste-Burel M, et al. SARS-CoV-2 T-cell responses in allogeneic hematopoietic stem cell recipients following two doses of BNT162b2 mRNA vaccine. Vaccines (Basel). 2022;10(3):448.
Ram R, Hagin D, Kikozashvilli N, et al. Safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in patients after allogeneic HCT or CD19-based CART therapy-a single-center prospective cohort study. Transplant Cell Ther. 2021;27(9):788-794.
Redjoul R, Le Bouter A, Parinet V, et al. Antibody response after third BNT162b2 dose in recipients of allogeneic HSCT. Lancet Haematol. 2021;8(10):e681-e683.
Einarsdottir S, Martner A, Waldenström J, et al. Deficiency of SARS-CoV-2 T-cell responses after vaccination in long-term allo-HSCT survivors translates into abated humoral immunity. Blood Adv. 2022;10;6(9):2723-2730.
Kimura Y, Hirabayashi E, Yano M, et al. COVID-19 Omicron variant-induced laryngitis. Auris Nasus Larynx. 2022:S0385-8146(22)00200-0. doi:10.1016/j.anl.2022.08.007

Auteurs

Umberto Pizzano (U)

Division of Hematology and Stem Cell Transplantation, University Hospital ASUFC, Udine, Italy.
Department of Medical Area (DAME), University of Udine, Udine, Italy.

Gabriele Facchin (G)

Division of Hematology and Stem Cell Transplantation, University Hospital ASUFC, Udine, Italy.
Department of Medical Area (DAME), University of Udine, Udine, Italy.

Chiara Marcon (C)

Division of Hematology and Stem Cell Transplantation, University Hospital ASUFC, Udine, Italy.
Department of Medical Area (DAME), University of Udine, Udine, Italy.

Martina Fabris (M)

Division of Laboratory Medicine, University Hospital ASUFC, Udine, Italy.

Marta Lisa Battista (ML)

Division of Hematology and Stem Cell Transplantation, University Hospital ASUFC, Udine, Italy.

Michela Cerno (M)

Division of Hematology and Stem Cell Transplantation, University Hospital ASUFC, Udine, Italy.

Antonella Geromin (A)

Division of Hematology and Stem Cell Transplantation, University Hospital ASUFC, Udine, Italy.

Martina Pucillo (M)

Division of Hematology and Stem Cell Transplantation, University Hospital ASUFC, Udine, Italy.
Department of Medical Area (DAME), University of Udine, Udine, Italy.

Giuseppe Petruzzellis (G)

Division of Hematology and Stem Cell Transplantation, University Hospital ASUFC, Udine, Italy.
Department of Medical Area (DAME), University of Udine, Udine, Italy.

Giampaolo Vianello (G)

Division of Hematology and Stem Cell Transplantation, University Hospital ASUFC, Udine, Italy.
Department of Medical Area (DAME), University of Udine, Udine, Italy.

Giulia Battaglia (G)

Division of Hematology and Stem Cell Transplantation, University Hospital ASUFC, Udine, Italy.
Department of Medical Area (DAME), University of Udine, Udine, Italy.

Roberto Peressutti (R)

Regional Transplant Centre, Friuli Venezia-Giulia Region, Udine, Italy.

Lucrezia Grillone (L)

Department of Medical Area (DAME), University of Udine, Udine, Italy.

Carlo Tascini (C)

Department of Medical Area (DAME), University of Udine, Udine, Italy.
Division of Infectious Diseases, University Hospital ASUFC, Udine, Italy.

Francesco Curcio (F)

Department of Medical Area (DAME), University of Udine, Udine, Italy.
Division of Laboratory Medicine, University Hospital ASUFC, Udine, Italy.

Renato Fanin (R)

Division of Hematology and Stem Cell Transplantation, University Hospital ASUFC, Udine, Italy.
Department of Medical Area (DAME), University of Udine, Udine, Italy.

Francesca Patriarca (F)

Division of Hematology and Stem Cell Transplantation, University Hospital ASUFC, Udine, Italy.
Department of Medical Area (DAME), University of Udine, Udine, Italy.

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