{"doi":"10.3390/immuno5020017","title":"Recurrent SARS-CoV-2 Infection Is Linked to the TLR7 rs179008 Variant and Related to Diminished Baseline T Cell Immunity","abstract":"<jats:p>Recurrent COVID-19, defined as two or more distinct episodes, may reflect an impaired immune response to SARS-CoV-2. In this case–control study, we compared three groups: individuals with recurrent COVID-19, those with a single episode, and SARS-CoV-2-naïve controls. We genotyped six immune-related SNPs, including TLR7 rs179008, and measured CD4+ and CD8+ T cell responses to SARS-CoV-2 antigens using flow cytometry. The T allele of TLR7 rs179008, previously linked to reduced receptor expression, was significantly overrepresented in the recurrent COVID-19 cohort. At baseline, frequencies of IFN-γ+, IL-2+, and TNF-α+ cells among CD4+ and CD8+ T cells did not differ between groups. However, stratification by the rs179008 genotype revealed that T allele carriers displayed diminished IFN-γ production in both CD4+ and CD8+ T cells and reduced IL-2 production in CD4+ T cells. Following vaccination, T cell responses were comparable across all genotypes. The T allele of TLR7 rs179008 is associated with recurrent COVID-19 and may contribute to impaired T cell-mediated immunity. Further studies are warranted to elucidate the mechanistic role of TLR7 variation in SARS-CoV-2 reinfection risk.</jats:p>","journal":"Immuno","year":2025,"id":638192,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":677909,"name":"Priscila Lima dos Santos","orcid":"0000-0002-8863-5718","position":1,"is_corresponding":false},{"id":1657441,"name":"Angela Maria da Silva","orcid":null,"position":2,"is_corresponding":false},{"id":953384,"name":"Lucas Sousa Magalhães","orcid":"0000-0002-2169-7463","position":3,"is_corresponding":false},{"id":499207,"name":"Camilla Natália Oliveira Santos","orcid":"0000-0002-9636-3935","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Recurrent SARS-CoV-2 Infection Is Linked to the TLR7 rs179008 Variant and Related to Diminished Baseline T Cell Immunity","abstract":"<jats:p>Recurrent COVID-19, defined as two or more distinct episodes, may reflect an impaired immune response to SARS-CoV-2. In this case–control study, we compared three groups: individuals with recurrent COVID-19, those with a single episode, and SARS-CoV-2-naïve controls. We genotyped six immune-related SNPs, including TLR7 rs179008, and measured CD4+ and CD8+ T cell responses to SARS-CoV-2 antigens using flow cytometry. The T allele of TLR7 rs179008, previously linked to reduced receptor expression, was significantly overrepresented in the recurrent COVID-19 cohort. At baseline, frequencies of IFN-γ+, IL-2+, and TNF-α+ cells among CD4+ and CD8+ T cells did not differ between groups. However, stratification by the rs179008 genotype revealed that T allele carriers displayed diminished IFN-γ production in both CD4+ and CD8+ T cells and reduced IL-2 production in CD4+ T cells. Following vaccination, T cell responses were comparable across all genotypes. The T allele of TLR7 rs179008 is associated with recurrent COVID-19 and may contribute to impaired T cell-mediated immunity. Further studies are warranted to elucidate the mechanistic role of TLR7 variation in SARS-CoV-2 reinfection risk.</jats:p>","is_dataset_classified":null,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19767382","pmcid":null,"openalex_id":"https://openalex.org/W4410444698","authors":[],"funders":[{"funder_name":"Conselho Nacional de Desenvolvimento Científico e Tecnológico","grant_id":"151365/2022-9","title":null}],"total_grants":1,"fwci":0.8286,"citation_percentile":0.6969464,"influential_citations":0,"citation_trend":[{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/2673-5601/5/2/17/pdf?version=1747379946","host_type":"journal"},{"url":"https://www.mdpi.com/2673-5601/5/2/17/pdf?version=1747379946","host_type":"publisher"},{"url":"https://www.mdpi.com/2673-5601/5/2/17/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/immuno5020017","host_type":"journal"},{"url":"https://doaj.org/article/b36228993b8047579ea8f372081496ec","host_type":"repository"}],"fields_of_study":["SARS-CoV-2 and COVID-19 Research","Immune Response and Inflammation","COVID-19 Clinical Research Studies"],"mesh_terms":[],"keywords":["Immunity","TLR7","Baseline (sea)","Virology","Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)","Coronavirus disease 2019 (COVID-19)","Biology","Medicine","Immunology","Innate immune system","Immune system","Internal medicine","Disease","Toll-like receptor"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T20:16:08.246299Z","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":[]}