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Previous studies reported dysregulated T\u2010cell function and lymphopenia in coronavirus disease\u201019 (COVID\u201019). However, immunopathological changes in the thymus associated with severe acute respiratory syndrome coronavirus\u20102 (SARS\u2010CoV\u20102) infection have not been elucidated. Here, we report that SARS\u2010CoV\u20102 infects thymocytes, and induces CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    (double positive; DP) T\u2010cell apoptosis leading to thymic atrophy and loss of peripheral TCR repertoire in K18\u2010hACE2 transgenic mice. Infected thymus led to increased CD44\n                    <jats:sup>+<\/jats:sup>\n                    CD25\n                    <jats:sup>\u2212<\/jats:sup>\n                    T\u2010cells, indicating an early arrest in the T\u2010cell maturation pathway. Thymic atrophy was notably higher in male hACE2\u2010Tg mice than in females and involved an upregulated de\u2010novo synthesis pathway of thymic glucocorticoid. Further, IFN\u2010\u03b3 was crucial for thymic atrophy, as anti\u2010IFN\u2010\u03b3 \u2010antibody neutralization blunted\u00a0thymic involution. Therapeutic use of Remdesivir also rescued thymic atrophy. While the Omicron variant and its sub\u2010lineage BA.5 variant caused marginal thymic atrophy, the delta variant of SARS\u2010CoV\u20102 exhibited severe thymic atrophy characterized by severely depleted DP T\u2010cells. Recently characterized broadly SARS\u2010CoV\u20102 neutralizing monoclonal antibody P4A2 was able to rescue thymic atrophy and restore the thymic maturation pathway of T\u2010cells. Together, we report SARS\u2010CoV\u20102\u2010associated thymic atrophy resulting from impaired T\u2010cell maturation pathway which may contribute to dyregulated T cell response during COVID\u201019.\n                  <\/jats:p>","DOI":"10.1002\/eji.202350624","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T06:23:57Z","timestamp":1713939837000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["SARS\u2010CoV\u20102 infection induces thymic atrophy mediated by IFN\u2010\u03b3 in hACE2 transgenic mice"],"prefix":"10.1002","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7850-5672","authenticated-orcid":false,"given":"Zaigham Abbas","family":"Rizvi","sequence":"first","affiliation":[{"name":"Immuno\u2010biology Lab, Infection and Immunology Centre, Translational Health Science and Technology Institute NCR\u2010Biotech Science Cluster  Faridabad Haryana 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Technology Institute NCR\u2010Biotech Science Cluster  Faridabad Haryana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puja","family":"Sharma","sequence":"additional","affiliation":[{"name":"Regional Centre Biotechnology NCR\u2010Biotech Science Cluster  Faridabad Haryana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshay","family":"Binayke","sequence":"additional","affiliation":[{"name":"Immuno\u2010biology Lab, Infection and Immunology Centre, Translational Health Science and Technology Institute NCR\u2010Biotech Science Cluster  Faridabad Haryana India"},{"name":"Immunology\u2010Core Lab, Translational Health Science and Technology Institute NCR\u2010Biotech Science Cluster  Faridabad Haryana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virendra","family":"Singh","sequence":"additional","affiliation":[{"name":"Immuno\u2010biology Lab, Infection and Immunology Centre, Translational Health Science and Technology Institute NCR\u2010Biotech Science Cluster  Faridabad Haryana India"},{"name":"Immunology\u2010Core Lab, Translational Health Science and Technology Institute NCR\u2010Biotech Science Cluster  Faridabad Haryana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinayaka","family":"Das","sequence":"additional","affiliation":[{"name":"Immuno\u2010biology Lab, Infection and Immunology Centre, Translational Health Science and Technology Institute NCR\u2010Biotech Science Cluster  Faridabad Haryana India"},{"name":"Immunology\u2010Core Lab, Translational Health Science and Technology Institute NCR\u2010Biotech Science Cluster  Faridabad Haryana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritika","family":"Khatri","sequence":"additional","affiliation":[{"name":"Infection and Immunology Centre, Translational Health Science and Technology Institute NCR\u2010Biotech Science Cluster  Faridabad Haryana 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