Immune Dysregulation in Post-COVID-19 Syndrome: A Comprehensive Review

Post-COVID-19 Syndrome (PCS), also known as Long COVID, is characterized by a range of persistent symptoms following acute SARS-CoV-2 infection, driven largely by immune dysregulation. This comprehensive review explores key immunological mechanisms underlying PCS, including chronic inflammation, autoimmunity, T-cell exhaustion, gut dysbiosis, and vascular abnormalities. Elevated inflammatory markers such as IL-6 and TNF-α, along with sustained autoantibody production and dysfunctional memory T-cell profiles, suggest ongoing immune activation long after viral clearance. The review highlights additional contributors such as mast cell hyperactivation and persistent viral antigens, which may sustain systemic symptoms. Notably, gut microbiota imbalance and endothelial damage further amplify immune disturbances. While some patients show immune normalization by 24 months, others continue to suffer from debilitating symptoms. Understanding these complex pathways is critical for developing targeted immunotherapies and personalized treatment approaches. This work aims to bridge current findings and support future clinical strategies for managing the multifaceted impact of Long COVID.