Long-Term Persistence of Dysregulated Lung-Resident Memory T Cells and Persistent Mucosal Inflammation in Post-COVID-19 Pulmonary Syndrome

Research Paper | 2026 | Volume 1 | Issue 01 | Page 36-41

Dr. Mohammad Samim Kuresi Khan Department of Respiratory Medicine, Dubai Medical College, UAE

Long-Term Persistence of Dysregulated Lung-Resident Memory T Cells and Persistent Mucosal .

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ABSTRACT

BACKGROUND: A significant proportion of COVID-19 survivors continue to suffer from Post-COVID-19 Pulmonary Syndrome (PCPS), characterized by persistent dyspnea, exercise intolerance, and radiographic lung abnormalities. While the initial hyper-inflammatory response is well-documented, the immunological mechanisms underlying the chronicity of these pulmonary symptoms remain poorly understood. This study investigates the hypothesis that PCPS is maintained by the long-term persistence of dysregulated lung-resident memory T cells (Trm) and ongoing mucosal inflammation. METHODS: We performed longitudinal immunophenotyping of bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMCs) from patients with PCPS (n=45) and recovered COVID-19 controls (n=30). Using flow cytometry, single-cell RNA sequencing (scRNA-seq), and multiplex cytokine assays, we characterized the activation state, exhaustion profile, and cytokine-secretion capacity of CD8+ and CD4+ Trm cells. Mucosal integrity was assessed via bronchial epithelial markers and inflammatory mediator quantification. RESULTS: PCPS patients exhibited a distinct population of lung-resident memory T cells characterized by a "hyper-activated-exhausted" phenotype (CD69+CD103+PD-1+TIGIT+). These cells showed constitutive expression of pro-inflammatory cytokines, specifically IL-17A, IFN-γ, and TNF-α, even in the absence of detectable viral antigens. Furthermore, the mucosal environment in PCPS patients displayed signs of chronic epithelial injury and sustained expression of CXCL10 and IL-6, correlating with the density and activation status of the Trm population. The presence of these dysregulated Trm cells was significantly associated with impaired diffusion capacity and persistent radiological fibrosis. CONCLUSION: Our findings demonstrate that PCPS is characterized by an enduring, dysregulated adaptive immune response localized within the lung mucosa. The persistence of these "memory" T cells, which continue to drive local inflammation long after viral clearance, provides a potential mechanistic basis for the chronicity of post-COVID lung disease and identifies the Trm cell niche as a critical therapeutic target for pulmonary rehabilitation. KEYWORDS: Post-COVID-19 Pulmonary Syndrome, Lung-Resident Memory T Cells (Trm), Mucosal Inflammation, Immunosenescence, CD8+ T cells, IL-17A,