{"doi":"10.1101/2022.04.07.487556","title":"SARS-CoV-2 and its variants, but not Omicron, induces thymic atrophy and impaired T cell development","abstract":"Abstract Pathogenic infections cause thymic atrophy, perturb thymic-T cell development and alter immunological response. Previous studies reported dysregulated T cell function and lymphopenia in coronavirus disease-19 (COVID-19) patients. However, immune-pathological changes, in the thymus, post severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection have not been elucidated. Here, we report SARS-CoV-2 infects thymocytes, depletes CD4+CD8+ (double positive; DP) T cell population associated with an increased apoptosis of thymocytes, which leads to severe thymic atrophy in K18-hACE2-Tg mice. CD44+CD25-T cells were found to be enriched in infected thymus, indicating an early arrest in the T cell developmental pathway. Further, Interferon gamma (IFN-γ) was crucial for thymic atrophy, as anti-IFN-γ antibody neutralization rescued the loss of thymic involution. Therapeutic use of remdesivir (prototype anti-viral drug) was also able to rescue thymic atrophy. While Omicron variant of SARS-CoV2 caused marginal thymic atrophy, delta variant of SARS-CoV-2 exhibited most profound thymic atrophy characterized by severely depleted DP T cells. Recently characterized broadly SARS-CoV-2 neutralizing monoclonal antibody P4A2 was able to rescue thymic atrophy and restore thymic developmental pathway of T cells. Together, we provide the first report of SARS-CoV-2 associated thymic atrophy resulting from impaired T cell developmental pathway and also explains dysregulated T cell function in COVID-19.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":298630,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9618,"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":863961,"name":"Srikanth Sadhu","orcid":null,"position":1,"is_corresponding":false},{"id":933833,"name":"Jyotsna Dandotiya","orcid":"0000-0002-7217-5980","position":2,"is_corresponding":false},{"id":987995,"name":"Akshay Binyka","orcid":null,"position":3,"is_corresponding":false},{"id":987996,"name":"Puja Sharma","orcid":null,"position":4,"is_corresponding":false},{"id":61370,"name":"Virendra Singh","orcid":"0000-0002-7342-3202","position":5,"is_corresponding":false},{"id":987997,"name":"Vinayaka Das","orcid":null,"position":6,"is_corresponding":false},{"id":863272,"name":"Ritika Khatri","orcid":"0000-0002-7930-8715","position":7,"is_corresponding":false},{"id":323267,"name":"Rajesh Kumar","orcid":"0000-0002-6744-0241","position":8,"is_corresponding":false},{"id":323265,"name":"Sweety Samal","orcid":"0000-0001-7894-8756","position":9,"is_corresponding":false},{"id":987643,"name":"Manjula Kalia","orcid":"0000-0002-3376-3659","position":10,"is_corresponding":false},{"id":51566,"name":"Amit Awasthi","orcid":"0000-0002-2563-1971","position":11,"is_corresponding":false},{"id":702087,"name":"Zaigham Abbas Rizvi","orcid":"0000-0001-7850-5672","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:31:36.269611Z","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":[]}