{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T04:35:17Z","timestamp":1782534917165,"version":"3.54.5"},"reference-count":54,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["2R15HL143545-02"],"award-info":[{"award-number":["2R15HL143545-02"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Tuberculosis and coronavirus disease 2019, also known as COVID-19, remain major global health challenges that disproportionately affect individuals with metabolic disorders, chronic inflammation, and limited access to healthcare. Although these diseases are caused by different pathogens, they share important host-related determinants of severity, including immune dysfunction, oxidative stress, endothelial injury, and maladaptive inflammatory responses. Glutathione, the primary intracellular antioxidant and a key regulator of redox balance, has emerged as an important host factor connecting these processes across infectious diseases. This review integrates experimental, translational, and clinical evidence supporting the role of glutathione in regulating immune function, oxidative stress, and tissue damage in tuberculosis and COVID-19. In tuberculosis, glutathione deficiency compromises macrophage antimicrobial activity, disrupts granuloma structure, and alters T helper cell responses, leading to impaired immune containment and disease progression. In COVID-19, reduced glutathione levels are associated with redox imbalance, excessive cytokine signaling, endothelial dysfunction, and thromboinflammatory complications, especially in high-risk populations. In both diseases, glutathione depletion reduces host resilience and increases vulnerability to severe outcomes through shared immune and vascular pathways. By unifying disease-specific findings within a host-directed framework, this review highlights glutathione and redox signaling as common vulnerability pathways that help explain overlapping risk profiles for severe tuberculosis and COVID-19. It also places glutathione biology within the broader context of host-directed immunotherapy, emphasizing its potential role in prevention-focused and resilience-based strategies that complement pathogen-targeted treatments. Although current evidence does not support simple claims of disease prevention, it provides strong mechanistic justification for further investigation of glutathione as a modifiable host factor in high-risk populations.<\/jats:p>","DOI":"10.3390\/antiox15020214","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T10:05:47Z","timestamp":1770372347000},"page":"214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Glutathione-Mediated Redox Regulation of Immune Dysfunction in COVID-19 and Tuberculosis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1860-3697","authenticated-orcid":false,"given":"John","family":"Dawi","sequence":"first","affiliation":[{"name":"College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scarlet","family":"Affa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Chemistry, The College, University of Los Angeles California, 405 Hilgard Avenue, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yura","family":"Misakyan","sequence":"additional","affiliation":[{"name":"College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Affa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Chemistry, The College, University of Los Angeles California, 405 Hilgard Avenue, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2586-1160","authenticated-orcid":false,"given":"Vishwanath","family":"Venketaraman","sequence":"additional","affiliation":[{"name":"College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"ref_1","unstructured":"GBD 2021 Tuberculosis Collaborators (2024). 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