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Cureus ; 14(6): e25738, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1912128


Allogeneic hematopoietic stem cell transplant (AHSCT) recipients are at a risk of developing immune-mediated tissue damage from activation of the donor's immunocompetent T cells by the recipient's normally expressed antigens, a phenomenon called graft-versus-host disease (GVHD). With the emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), new vaccines have been developed to prevent morbidity and mortality, including the highly vulnerable hematologic malignancy patients after undergoing AHSCT. The early pathophysiologic events in GVHD include priming the donor T cells with molecules that are endogenous or pathogenic. In this case series, we present two cases of AHSCT recipients in which the SARS-CoV-2 vaccination series proceeded the development of GVHD manifesting with oral mucosal symptoms and derangement in the liver function tests. Our experience raises the question if any of the vaccine components serve as a molecular trigger for GVHD, making the current SARS-CoV-2 vaccines a risk factor for activating the immune system and developing GVHD.

Br J Haematol ; 198(4): 668-679, 2022 08.
Article in English | MEDLINE | ID: covidwho-1874397


Allogeneic haematopoietic stem cell transplant (HSCT) recipients remain at high risk of adverse outcomes from coronavirus disease 2019 (COVID-19) and emerging variants. The optimal prophylactic vaccine strategy for this cohort is not defined. T cell-mediated immunity is a critical component of graft-versus-tumour effect and in determining vaccine immunogenicity. Using validated anti-spike (S) immunoglobulin G (IgG) and S-specific interferon-gamma enzyme-linked immunospot (IFNγ-ELIspot) assays we analysed response to a two-dose vaccination schedule (either BNT162b2 or ChAdOx1) in 33 HSCT recipients at ≤2 years from transplant, alongside vaccine-matched healthy controls (HCs). After two vaccines, infection-naïve HSCT recipients had a significantly lower rate of seroconversion compared to infection-naïve HCs (25/32 HSCT vs. 39/39 HCs no responders) and had lower S-specific T-cell responses. The HSCT recipients who received BNT162b2 had a higher rate of seroconversion compared to ChAdOx1 (89% vs. 74%) and significantly higher anti-S IgG titres (p = 0.022). S-specific T-cell responses were seen after one vaccine in HCs and HSCT recipients. However, two vaccines enhanced S-specific T-cell responses in HCs but not in the majority of HSCT recipients. These data demonstrate limited immunogenicity of two-dose vaccination strategies in HSCT recipients, bolstering evidence of the need for additional boosters and/or alternative prophylactic measures in this group.

COVID-19 Vaccines , COVID-19 , Hematopoietic Stem Cell Transplantation , Age Factors , Antibodies, Viral/immunology , BNT162 Vaccine/immunology , BNT162 Vaccine/therapeutic use , Bone Marrow Transplantation/adverse effects , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , COVID-19 Vaccines/pharmacology , COVID-19 Vaccines/therapeutic use , ChAdOx1 nCoV-19/immunology , ChAdOx1 nCoV-19/therapeutic use , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Immunity, Cellular/drug effects , Immunity, Cellular/immunology , Immunity, Humoral/drug effects , Immunity, Humoral/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Seroconversion , Transplantation, Homologous/adverse effects , Vaccination/adverse effects