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

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. ### Competing Interest Statement University of Pittsburgh Patent 9606019 author: RS describes CMI testing for CMV is licensed exclusively to Plexision in which University and RS own equity. RS and CA developed Plexisions patent-pending multi-variate CMI assay for SARS2. RS is Professor of Surgery at the University of Pittsburgh and Chief Scientific Officer of Plexision by permission of COI committee at the University. CA and BH are paid consultants to Plexision. Other authors have nothing to disclose. * (CMI) : cell-mediated immunity (SARS2) : SARS-CoV-2 (H-NT) : healthy-non transplant (H-Tr) : healthy transplant (Tr) : COVID-19 transplant (NT) : COVID-19 non-transplant (TP) : true positive (FN) : false negative (PBL) : peripheral blood leukocytes (M-MDSC and P-MDSC) : monocytic- and polymorphonuclear-MDSC