{"doi":"10.1172/jci149125","title":"Relationship of SARS-CoV-2–specific CD4 response to COVID-19 severity and impact of HIV-1 and tuberculosis coinfection","abstract":"T cells are involved in control of coronavirus disease 2019 (COVID-19), but limited knowledge is available on the relationship between antigen-specific T cell response and disease severity. Here, we used flow cytometry to assess the magnitude, function, and phenotype of SARS coronavirus 2-specific (SARS-CoV-2-specific) CD4+ T cells in 95 hospitalized COVID-19 patients, 38 of them being HIV-1 and/or tuberculosis (TB) coinfected, and 38 non-COVID-19 patients. We showed that SARS-CoV-2-specific CD4+ T cell attributes, rather than magnitude, were associated with disease severity, with severe disease being characterized by poor polyfunctional potential, reduced proliferation capacity, and enhanced HLA-DR expression. Moreover, HIV-1 and TB coinfection skewed the SARS-CoV-2 T cell response. HIV-1-mediated CD4+ T cell depletion associated with suboptimal T cell and humoral immune responses to SARS-CoV-2, and a decrease in the polyfunctional capacity of SARS-CoV-2-specific CD4+ T cells was observed in COVID-19 patients with active TB. Our results also revealed that COVID-19 patients displayed reduced frequency of Mycobacterium tuberculosis-specific CD4+ T cells, with possible implications for TB disease progression. These results corroborate the important role of SARS-CoV-2-specific T cells in COVID-19 pathogenesis and support the concept of altered T cell functions in patients with severe disease.","journal":"Journal of Clinical Investigation","year":2021,"id":147087,"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":176,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9509,"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":330708,"name":"Elsa Du Bruyn","orcid":"0000-0002-5088-2158","position":1,"is_corresponding":false},{"id":560703,"name":"Cari Stek","orcid":"0000-0001-8813-0819","position":2,"is_corresponding":false},{"id":110207,"name":"Remy Daroowala","orcid":null,"position":3,"is_corresponding":false},{"id":330709,"name":"René Goliath","orcid":"0000-0001-9818-4634","position":4,"is_corresponding":false},{"id":626907,"name":"Fatima Abrahams","orcid":null,"position":5,"is_corresponding":false},{"id":625648,"name":"Qonita Said-Hartley","orcid":"0000-0001-5962-5222","position":6,"is_corresponding":false},{"id":625649,"name":"Brian Allwood","orcid":"0000-0003-0421-2978","position":7,"is_corresponding":false},{"id":614572,"name":"Marvin Hsiao","orcid":"0000-0003-4926-6216","position":8,"is_corresponding":false},{"id":266680,"name":"Katalin A. Wilkinson","orcid":"0000-0002-9796-2040","position":9,"is_corresponding":false},{"id":230241,"name":"Cecilia S. Lindestam Arlehamn","orcid":"0000-0001-7302-8002","position":10,"is_corresponding":false},{"id":55670,"name":"Alessandro Sette","orcid":"0000-0001-7013-2250","position":11,"is_corresponding":false},{"id":308893,"name":"Sean Wasserman","orcid":"0000-0002-3508-6719","position":12,"is_corresponding":false},{"id":266683,"name":"Robert J. Wilkinson","orcid":"0000-0002-2753-1800","position":13,"is_corresponding":false},{"id":330707,"name":"Catherine Riou","orcid":"0000-0001-9679-0745","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-18T23:42:30.206628Z","pmid":"33945513","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":[]}