ABSTRACT
Since the emergence of the Omicron variant of SARS-CoV-2, though considered less virulent, hospitalization and death rates among immunocompromised patients remain high, especially for poor responders to vaccination. We conducted a retrospective multicentric study to evaluate pre-exposure prophylaxis with AZD7442 (tixagevimab/cilgavimab) for preventing COVID-19 in adult allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. Among the 161 patients of our cohort, 22 (14%) contracted COVID-19 after a median follow-up of 105 days, but no severe form was observed. Only one major adverse event was reported: an acute coronary syndrome, resolved without sequelae. Pending randomized controlled trial results, our data support the use of AZD7442 as pre-exposure prophylaxis for COVID-19 during Omicron wave in allo-HSCT patients who failed to develop humoral immunity to vaccination, to prevent severe and potentially lethal forms of SARS-CoV-2 infection.
Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Pre-Exposure Prophylaxis , Adult , Humans , Retrospective Studies , COVID-19/prevention & control , SARS-CoV-2 , Hematopoietic Stem Cell Transplantation/adverse effectsABSTRACT
A full exploration of immune responses is deserved after anti-SARS-CoV-2 vaccination and boosters, especially in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although several reports indicate successful humoral responses in such patients, the literature is scarce on cellular specific immunity. Here, both B- (antibodies) and T-cell responses were explored after one (V3 n = 40) or two (V4 n = 12) BNT162b2 mRNA vaccine boosters in 52 allo-HSCT recipients at a median of 755 days post-transplant (<1 year n = 9). Results were compared with those of 12 controls who had received only one booster (BNT162b2 n = 6; mRNA-1273 n = 6). All controls developed protective antibody levels (>250 BAU/mL) and anti-spike T-cell responses. Similarly, 81% of the patients developed protective antibody levels, without difference between V3 and V4 (82.5% vs. 75%, p = 0.63), and 85% displayed T-cell responses. The median frequency of anti-spike T cells did not differ either between controls or the whole cohort of patients, although it was significantly lower for V3 (but not V4) patients. COVID-19 infections were solely observed in individuals having received only one booster. These results indicate that four vaccine injections help to achieve a satisfactory level of both humoral and cellular immune protection in allo-HSCT patients.
Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Vaccines , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , Hematopoietic Stem Cell Transplantation/methods , Hematopoietic Stem Cells , Humans , Immunization, Secondary , SARS-CoV-2 , T-Lymphocytes , Vaccines, Synthetic , mRNA VaccinesABSTRACT
This study reports the effectiveness of three injections of BNT162b2 anti-SARS-CoV-2 mRNA vaccine in 141 Allo-HSCT recipients with a median follow-up of 6 months post-third shot. We demonstrate a long-term high protection of Allo-HSCT recipients since only 2 infections and one death related to COVID-19 occurred.
ABSTRACT
Little is known about the immune response to SARS-CoV-2 vaccination in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, several studies have reported that adequate protection could be provided to this population. The purpose of this study was to evaluate which factors can predict the efficacy of SARS-CoV-2 vaccination in these specifically immunosuppressed patients. Specific anti-Spike (S) antibody responses were assessed in a cohort of 117 allo-HSCT recipients after 2 injections of BNT162b2 mRNA SARS-CoV-2 vaccine (V1 and V2). Factors considered liable to influence the antibody response and analyzed in this series were the interval between allo-HSCT and V1, donor source, recipient and donor age, current immunosuppressive/chemotherapy (I/C) treatment, and levels of CD4+and CD8+ T cells, B cells, and natural killer cells at the time of V1. Overall, the S-antibody response rate, evaluated at a median of 35 days after V2, was 82.9% for the entire cohort, with 71 patients (61%) reaching the highest titer. In univariate analysis, a lower pre-V1 median total lymphocyte count, lower CD4+ T cell and B cell counts, ongoing I/C treatment, and a haploidentical donor were characteristic of nonhumoral responders. However, multiparameter analysis showed that B cell aplasia was the sole factor predicting the absence of a specific immune response (odds ratio, 0.01; 95% confidence interval, 0.00 to 0.10; P < 10-3). Indeed, the rate of humoral response was 9.1% in patients with B cell aplasia versus 95.9% in patients with a B cell count >0 (P < 10-9). These results advocate for the administration of anti-SARS-CoV-2 vaccination in allo-HSCT recipients as early as peripheral B cell levels can be detected, and also suggest the need for close monitoring of B-cell reconstitution after Allo-HSCT.
Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , BNT162 Vaccine , Biomarkers , CD8-Positive T-Lymphocytes , COVID-19/prevention & control , COVID-19 Vaccines , Hematopoietic Stem Cell Transplantation/methods , Humans , RNA, Messenger , SARS-CoV-2 , VaccinationABSTRACT
BACKGROUND: At variance to humoral responses, cellular immunity after anti-SARS-CoV-2 vaccines has been poorly explored in recipients of allogeneic hematopoietic stem-cell transplantation (Allo-HSCT), especially within the first post-transplant years where immunosuppression is more profound and harmful. METHODS: SARS-CoV-2 Spike protein-specific T-cell responses were explored after two doses of BNT162b2 mRNA vaccine in 45 Allo-HSCT recipients with a median time from transplant of less than 2 years by using INF-γ ELISPOT assay and flow-cytometry enumeration of CD4+ and CD8+ T lymphocytes with intracellular cytokine production of IFN-γ and TNF-α. RESULTS: A strong TNF-α+ response from SARS-CoV-2-specific CD4+ T-cells was detected in a majority of humoral responders (89%) as well as in a consistent population of non-humoral responders (40%). CONCLUSIONS: T-cells are likely to participate in protection against COVID-19 viral infection, even in the absence of detectable antibody response, especially in the first years post-transplant in Allo-HSCT recipients.
Subject(s)
2019-nCoV Vaccine mRNA-1273/administration & dosage , Antibodies, Viral/biosynthesis , BNT162 Vaccine/administration & dosage , COVID-19/immunology , COVID-19/prevention & control , Hematopoietic Stem Cell Transplantation/adverse effects , SARS-CoV-2/immunology , Aged , Allografts , Antibodies, Viral/blood , Dose-Response Relationship, Immunologic , Female , Humans , Immunization, Secondary , Immunocompromised Host/immunology , Immunogenicity, Vaccine , Male , Middle Aged , Multivariate Analysis , Retrospective StudiesSubject(s)
BNT162 Vaccine/therapeutic use , COVID-19/prevention & control , Adult , Aged , Allografts , Antibodies, Viral/immunology , Antibody Formation , BNT162 Vaccine/administration & dosage , COVID-19/immunology , Female , Humans , Male , Middle Aged , Organ Transplantation , Retrospective Studies , SARS-CoV-2/immunology , Stem Cell Transplantation , Transplantation, Homologous , Young AdultSubject(s)
Antibodies, Viral/biosynthesis , BNT162 Vaccine/immunology , COVID-19/prevention & control , Immunoglobulin G/biosynthesis , Immunotherapy, Adoptive , SARS-CoV-2/immunology , Adult , Aged , Antigens, Viral/immunology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , BNT162 Vaccine/adverse effects , Biological Products/therapeutic use , Combined Modality Therapy , Female , Fever/etiology , Hematopoietic Stem Cell Transplantation , Humans , Immunization, Secondary , Immunocompromised Host , Immunogenicity, Vaccine , Lymphoma, Non-Hodgkin/immunology , Lymphoma, Non-Hodgkin/therapy , Male , Middle Aged , Pain/etiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Receptors, Antigen, T-Cell/therapeutic use , Receptors, Chimeric Antigen/therapeutic use , Spike Glycoprotein, Coronavirus/immunology , Vaccination , Young AdultABSTRACT
This was a monocentric prospective study testing the efficacy and safety of a first injection of BNT162b2 (Pfizer-BioNTech) in 112 Allo-HSCT patients. Antibody response to SARS-CoV-2 spike protein receptor-binding domain was tested at the time of the second injection (Roche Elecsys). The study also included a non-randomized control arm of 26 healthy controls. This study shows that a first dose of SARS-CoV-2 messenger RNA vaccine is safe and provides a 55% rate of seroconversion in allotransplanted patients compared to 100% for the controls (p < 0.001). Factors influencing the absence of response in patients were recent transplantation (<2 years), lymphopenia (<1 × 109/L) and immunosuppressive treatment or chemotherapy at the time of vaccination.