Post-Acute COVID-19 Pathophysiology: Cellular Stress Responses, Immune Dysregulation, and Biochemical Signatures in Recovery Phase.

Abstract

Background/aims: Post-acute COVID-19 syndrome (PACS) presents with persistent symptoms such as fatigue, dyspnea, and cognitive impairment, even after apparent clinical recovery. Although widely reported, the biological basis of these symptoms remains unclear. This study aimed to investigate the underlying cellular, immunological, oxidative, and biochemical disturbances during the recovery phase of COVID-19 and evaluate their association with clinical symptomatology.

Methods: A cross-sectional observational study was conducted involving 120 participants who were previously SARS-CoV-2 positive, recruited ≥30 days post-recovery. Peripheral blood samples were analyzed for ER stress markers (HSP70, CHOP, GRP78), Pro- and anti-inflammatory cytokines (IL-6, TNF-α, IFN-γ, IL-10), oxidative biomarkers (MDA, SOD, GSH), and biochemical parameters (ALT, AST, CRP, ferritin). T cell subsets were evaluated via flow cytometry. Statistical comparisons and correlation analyses were performed using SPSS v22.0.

Results: Significant elevations were observed in all stress and inflammatory markers (p < 0.05). IL-6, CRP, and MDA showed strong positive correlations with fatigue and dyspnea scores. Treg percentages were reduced, and males exhibited higher biomarker levels than females. Persistent immune and oxidative activation was evident in the recovery phase.

Conclusion: Post-acute COVID-19 is associated with quantifiable cellular and molecular disturbances. This integrated analysis of ER stress, immune dysregulation, and oxidative imbalance provides a novel and comprehensive view of long COVID pathophysiology.