{"doi":"10.1101/2022.01.25.22269670","title":"TNFα-producing CD4 <sup>+</sup> T cells dominate the SARS-CoV-2-specific T cell response in COVID-19 outpatients and are associated with durable antibodies","abstract":"Abstract SARS-CoV-2-specific CD4 + T cells are likely important in immunity against COVID-19, but our understanding of CD4 + longitudinal dynamics following infection and specific features that correlate with the maintenance of neutralizing antibodies remains limited. We characterized SARS-CoV-2-specific CD4 + T cells in a longitudinal cohort of 109 COVID-19 outpatients. The quality of the SARS-CoV-2-specific CD4 + response shifted from cells producing IFNγ to TNFα + from five days to four months post-enrollment, with IFNγ - IL21 - TNFα + CD4 + T cells the predominant population detected at later timepoints. Greater percentages of IFNγ - IL21 - TNFα + CD4 + T cells on day 28 correlated with SARS-CoV-2 neutralizing antibodies measured seven months post-infection (ρ=0.4, P=0.01). mRNA vaccination following SARS-CoV-2 infection boosted both IFNγ and TNFα producing, spike protein-specific CD4 + T cells. These data suggest that SARS-CoV-2-specific, TNFα-producing CD4 + T cells may play an important role in antibody maintenance following COVID-19.","journal":"medRxiv","year":2022,"id":305673,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9595,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":883550,"name":"Adam S. Kirosingh","orcid":"0000-0003-0500-9269","position":1,"is_corresponding":false},{"id":1000080,"name":"Diego Alonzo Martinez Mori","orcid":null,"position":2,"is_corresponding":false},{"id":233135,"name":"Saborni Chakraborty","orcid":"0000-0003-0502-3757","position":3,"is_corresponding":false},{"id":21593,"name":"Zicheng Hu","orcid":"0000-0002-4168-1725","position":4,"is_corresponding":false},{"id":1000081,"name":"Benjamin L. Seivers","orcid":null,"position":5,"is_corresponding":false},{"id":264386,"name":"Karen B. Jacobson","orcid":"0000-0003-3050-4595","position":6,"is_corresponding":false},{"id":264385,"name":"Hector Bonilla","orcid":"0000-0002-0513-8733","position":7,"is_corresponding":false},{"id":231939,"name":"Julie Parsonnet","orcid":"0000-0001-7342-5366","position":8,"is_corresponding":false},{"id":231886,"name":"Jason R. Andrews","orcid":"0000-0002-5967-251X","position":9,"is_corresponding":false},{"id":621776,"name":"Kathleen D. Press","orcid":"0000-0002-6548-7513","position":10,"is_corresponding":false},{"id":621777,"name":"Maureen Ty","orcid":"0000-0001-5108-7714","position":11,"is_corresponding":false},{"id":511071,"name":"Daniel Ruiz‐Betancourt","orcid":null,"position":12,"is_corresponding":false},{"id":622604,"name":"Lauren de la Parte","orcid":null,"position":13,"is_corresponding":false},{"id":793172,"name":"Gene S. Tan","orcid":"0000-0002-8965-1509","position":14,"is_corresponding":false},{"id":52017,"name":"Catherine A. Blish","orcid":"0000-0001-6946-7627","position":15,"is_corresponding":false},{"id":435847,"name":"Saki Takahashi","orcid":"0000-0001-5413-5507","position":16,"is_corresponding":false},{"id":107136,"name":"Isabel Rodríguez-Barraquer","orcid":"0000-0001-6784-1021","position":17,"is_corresponding":false},{"id":299001,"name":"Bryan Greenhouse","orcid":"0000-0003-0287-9111","position":18,"is_corresponding":false},{"id":233142,"name":"Upinder Singh","orcid":"0000-0003-0630-0306","position":19,"is_corresponding":false},{"id":103717,"name":"Taia T. Wang","orcid":"0000-0002-3894-685X","position":20,"is_corresponding":false},{"id":233149,"name":"Prasanna Jagannathan","orcid":"0000-0001-6305-758X","position":21,"is_corresponding":false},{"id":407208,"name":"Kattria van der Ploeg","orcid":"0000-0002-3183-3190","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:32:44.983506Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}