{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:04:42Z","timestamp":1753891482796,"version":"3.41.2"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T00:00:00Z","timestamp":1747612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The chronic nature of latent tuberculosis infection (LTBI) allows it to coexist with diverse pathologies. However, it remains unclear whether immune alterations associated with LTBI influence COVID-19 coinfection and patient outcomes. This study aims to compare the immune phenotype of patients with LTBI\/COVID-19 to those with COVID-19 alone, in order to assess whether latent tuberculosis infection induces significant immune cell alterations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Peripheral blood mononuclear cells were cultured and stimulated with the SARS-CoV-2 Spike protein and <jats:italic>Mycobacterium bovis<\/jats:italic> Bacillus Calmette-Gu\u00e9rin (<jats:italic>M. bovis<\/jats:italic> BCG) to evaluate cellular distribution and function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>the LTBI\/COVID-19 group exhibited a narrower range of symptoms and required less complex treatment regimens than the COVID-19 group. The cellular evaluation revealed that individuals with COVID-19 displayed a distinct immune profile, characterized by a predominance of monocytes expressing pro-inflammatory and regulatory markers, including TNFR2, HLA-DR+TNFR2, and CD71. While CD4+ T cell subpopulation distribution and function were similar across groups, LTBI\/COVID-19 and COVID-19 exhibited similar frequencies of CD8+perforin+ and CD8+Granzime B+ T cells. However, LTBI\/COVID-19 displays lower soluble levels of granzyme B and perforin in culture supernatants and perforin, granulysin, and sFas in plasma compared to COVID-19. Notably, CD8+ T cells from LTBI\/COVID-19 showed higher antigen-specific degranulation than COVID-19. Moreover, LTBI\/COVID-19 individuals predominantly displayed CD4+ and CD8+ T cells with highly polarized, compact mitochondria at baseline, which remained unchanged under stimulation. In contrast, COVID-19 had T cells with highly polarized, fragmented mitochondria at baseline, a profile that persisted under stimulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The findings reveal significant alterations in monocytes and T cells of individuals with LTBI\/COVID-19, suggesting that co-infection may induce changes in the cellular phenotype and cytotoxic function of CD8 T cells.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1566449","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T05:15:03Z","timestamp":1747631703000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Latent tuberculosis coinfection in mild COVID-19 is associated with a distinct immune cell phenotype marked by enhanced cytotoxic degranulation and mitochondrial 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