{"doi":"10.1101/2021.05.03.442371","title":"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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":215084,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9546,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":809295,"name":"Vinayak Rohan","orcid":"0000-0002-5975-032X","position":1,"is_corresponding":false},{"id":239668,"name":"Alexander Kroemer","orcid":"0000-0002-9842-4973","position":2,"is_corresponding":false},{"id":679600,"name":"Sohail Rao","orcid":"0000-0001-5027-9992","position":3,"is_corresponding":false},{"id":286076,"name":"George Mazariegos","orcid":"0000-0002-2624-8632","position":4,"is_corresponding":false},{"id":226362,"name":"Brandon W. Higgs","orcid":"0000-0002-2951-0245","position":5,"is_corresponding":false},{"id":661549,"name":"Satish N. Nadig","orcid":"0000-0001-6090-4245","position":6,"is_corresponding":false},{"id":680733,"name":"Jose Luis Almeda","orcid":null,"position":7,"is_corresponding":false},{"id":633939,"name":"Harmeet Dhani","orcid":"0000-0001-6541-7980","position":8,"is_corresponding":false},{"id":809296,"name":"Khalid Khan","orcid":"0000-0002-2574-9232","position":9,"is_corresponding":false},{"id":809297,"name":"Nada Yazigi","orcid":"0000-0002-6436-4343","position":10,"is_corresponding":false},{"id":809298,"name":"Udeme D. Ekong","orcid":"0000-0002-3312-112X","position":11,"is_corresponding":false},{"id":809299,"name":"Stuart S. Kaufman","orcid":"0000-0002-5308-4565","position":12,"is_corresponding":false},{"id":679601,"name":"Monica M. Betancourt-Garcia","orcid":"0000-0002-7028-5035","position":13,"is_corresponding":false},{"id":277294,"name":"Kavitha Mukund","orcid":"0000-0002-3570-2315","position":14,"is_corresponding":false},{"id":809787,"name":"Pradeep Sethi","orcid":null,"position":15,"is_corresponding":false},{"id":242937,"name":"Shikhar Mehrotra","orcid":"0000-0002-5411-9504","position":16,"is_corresponding":false},{"id":809300,"name":"Kyle Soltys","orcid":"0000-0002-0899-7234","position":17,"is_corresponding":false},{"id":809301,"name":"Manasi Singh","orcid":"0000-0001-6175-0858","position":18,"is_corresponding":false},{"id":809788,"name":"Geoffrey Bond","orcid":null,"position":19,"is_corresponding":false},{"id":809789,"name":"Ajai Khanna","orcid":null,"position":20,"is_corresponding":false},{"id":501135,"name":"Mylarappa Ningappa","orcid":"0000-0002-5238-8663","position":21,"is_corresponding":false},{"id":809790,"name":"Brianna Spishock","orcid":null,"position":22,"is_corresponding":false},{"id":809791,"name":"Elizabeth Sindhi","orcid":null,"position":23,"is_corresponding":false},{"id":809302,"name":"Neha Atale","orcid":"0000-0003-2683-9464","position":24,"is_corresponding":false},{"id":809792,"name":"Maggie Saunders","orcid":null,"position":25,"is_corresponding":false},{"id":749302,"name":"Prabhakar K. 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