AUTHOR=Peña-Bates Carlos , Ramón-Luing Lucero A. , Flores-Gonzalez Julio , Espinosa Enrique , Martinez-Moreno María F. , Medina-Quero Karen , Vargas-Hernandez Marco A. , Téllez-Navarrete Norma A. , Sosa-Gomez Fernando M. , Becerril-Vargas Eduardo , Salazar Miguel Ángel , Chavez-Galan Leslie 

TITLE=Latent tuberculosis coinfection in mild COVID-19 is associated with a distinct immune cell phenotype marked by enhanced cytotoxic degranulation and mitochondrial alterations

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1566449

DOI=10.3389/fimmu.2025.1566449

ISSN=1664-3224

ABSTRACT=IntroductionThe 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.MethodsPeripheral blood mononuclear cells were cultured and stimulated with the SARS-CoV-2 Spike protein and Mycobacterium bovis Bacillus Calmette-Guérin (M. bovis BCG) to evaluate cellular distribution and function.Resultsthe 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.ConclusionThe 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.