Impaired T-cell and antibody immunity after COVID-19 infection in chronically immunosuppressed transplant recipients

Abstract

Assessment of T-cell immunity to the COVID-19 coronavirus requires reliable assays and is of great interest, given the uncertain longevity of the antibody response. Some recent reports have used immunodominant spike (S) antigenic peptides and anti-CD28 co-stimulation in varying combinations to assess T-cell immunity to SARS-CoV-2. These assays may cause T-cell hyperstimulation and could overestimate antiviral immunity in chronically immunosuppressed transplant recipients, who are predisposed to infections and vaccination failures. Here, we evaluate CD154-expressing T-cells induced by unselected S antigenic peptides in 204 subjects-103 COVID-19 patients and 101 healthy unexposed subjects. Subjects included 72 transplanted and 130 non-transplanted subjects. S-reactive CD154+T-cells co-express and can thus substitute for IFNγ (n=3). Assay reproducibility in a variety of conditions was acceptable with coefficient of variation of 2-10.6%. S-reactive CD154+T-cell frequencies were a) higher in 42 healthy unexposed transplant recipients who were sampled pre-pandemic, compared with 59 healthy non-transplanted subjects (p=0.02), b) lower in Tr COVID-19 patients compared with healthy transplant patients (p<0.0001), c) lower in Tr patients with severe COVID-19 (p<0.0001), or COVID-19 requiring hospitalization (p<0.05), compared with healthy Tr recipients. S-reactive T-cells were not significantly different between the various COVID-19 disease categories in NT recipients. Among transplant recipients with COVID-19, cytomegalovirus co-infection occurred in 34%; further, CMV-specific T-cells (p<0.001) and incidence of anti-receptor-binding-domain IgG (p=0.011) were lower compared with non-transplanted COVID-19 patients. Healthy unexposed transplant recipients exhibit pre-existing T-cell immunity to SARS-CoV-2. COVID-19 infection leads to impaired T-cell and antibody responses to SARS-CoV-2 and increased risk of CMV co-infection in transplant recipients.

T-cell and antibody immunity after COVID-19 mRNA vaccines in healthy and immunocompromised subjects-An exploratory study

“…PBL from each healthy subject, obtained pre-vaccination and at 2 weeks after each vaccination dose from healthy subjects were stimulated overnight with overlapping peptides mixtures representing the S1, S2 and S antigenic sequences as described previously 6 (JPT Peptides, Germany). The frequencies of CD3, CD4, and CD8 cells that expressed CD154 after overnight stimulation with S antigenic peptides were measured with flow cytometry as described previously 6 . These frequencies were also measured in single samples obtained from 7 IC subjects.…”

“…We have recently described decreased spike-antigen-reactive T-cells and IgG antibodies to the receptor binding domain (RBD) of the spike protein early after COVID-19 infection in chronically immunosuppressed transplant patients 6 . The S antigenic sequence is comprised of the less conserved N-terminal S1 component, which contains the receptor binding domain (RBD), and the conserved C-terminal S2 sequence 7 .…”

“…The S antigenic sequence is comprised of the less conserved N-terminal S1 component, which contains the receptor binding domain (RBD), and the conserved C-terminal S2 sequence 7 . The T-cell assay uses CD154, which is co-expressed with interferon gamma (IFNγ) upon S antigen stimulation, as the single marker of viral-antigen-specific T-cells 6,8 . Assay reproducibility is reflected by a coefficient of variation ranging from 2-10.6% under a variety of conditions 6 .…”

“…The T-cell assay uses CD154, which is co-expressed with interferon gamma (IFNγ) upon S antigen stimulation, as the single marker of viral-antigen-specific T-cells 6,8 . Assay reproducibility is reflected by a coefficient of variation ranging from 2-10.6% under a variety of conditions 6 . In our recent study, Impaired T-cell responses to S antigen were accompanied by an increase in circulating myeloid derived suppressor cells (MDSC) early after COVID-19 infection 6 .…”

“…Assay reproducibility is reflected by a coefficient of variation ranging from 2-10.6% under a variety of conditions 6 . In our recent study, Impaired T-cell responses to S antigen were accompanied by an increase in circulating myeloid derived suppressor cells (MDSC) early after COVID-19 infection 6 . These cells arise during acute viral infections and suppress T-cells 9 .…”