Circulating Drivers of Pathophysiology in Post-COVID-19 Sequelae

Introduction: According to the WHO, post-COVID-19 sequelae impose an increased burden of illness and comorbidities among survivors. The present study evaluated systemic clinical complications associated with the dysregulation of circulatory cytokines in post-COVID-19 patients and compared them with those of healthy controls. Methods: This cross-sectional study included 147 participants divided into symptomatic post-COVID-19, asymptomatic post-COVID-19, and healthy control groups. After obtaining informed consent, peripheral blood samples were collected and analyzed using ELISA and RT-qPCR. Circulating levels of pro-inflammatory (IL-6, IL-1β, TNFα) and anti-inflammatory cytokine IL-10 were measured in relation to clinical sequelae. Results: Common symptoms were fatigue (48%), headache (48%), anxiety (64%), general weakness (70%), muscle pain (70%), joint pain (54%), chest pain (32%), dyspnea (36%), and post-activity tachypnea (40%) among post COVID-19 individulas. A higher prevalence of post-COVID-19 sequelae was observed in females aged >40 years and in those with a post-COVID-19 duration of <30 months. ELISA showed higher levels of IL-6, TNF-α, and IL-10 in post-COVID-19 patients than in controls (p < 0.01). RT-qPCR revealed upregulation of IL-6, TNF-α, IL-1β, and IL-10 mRNA, which correlated with post-COVID-19 sequelae (p < 0.01). Discussion: Older age and shorter duration of post-COVID-19 are associated with more symptom burden, implying incomplete immune recovery during early convalescence. Elevated IL-6, IL-1β, TNF-α, and IL-10 levels indicate persistent immune dysregulation, supporting the view that post-COVID-19 is a chronic inflammatory state with clinical effects. Conclusion: IL-6, TNFα, IL-1β, and IL-10 are dysregulated in post-COVID-19 systemic sequelae, and longitudinal studies are necessary to better understand and potentially reduce this dysregulation in post-COVID-19.