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

Ashokkumar, Chethan; Rohan, Vinayak; Kroemer, Alexander H; Rao, Sohail; Mazariegos, George; Higgs, Brandon W; Nadig, Satish; Almeda, Jose; Dhani, Harmeet; Khan, Khalid; Yazigi, Nada; Ekong, Udeme; Kaufman, Stuart; Betancourt-Garcia, Monica M; Mukund, Kavitha; Sethi, Pradeep; Mehrotra, Shikhar; Soltys, Kyle; Singh, Manasi S; Bond, Geoffrey; Khanna, Ajai; Ningappa, Mylarappa; Spishock, Brianna; Sindhi, Elizabeth; Atale, Neha; Saunders, Maggie; Baliga, Prabhakar; Fishbein, Thomas; Subramaniam, Shankar; Sindhi, Rakesh

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.