Background: Long coronavirus disease (COVID), or post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a multi-system condition associated with persistent immune dysregulation, autoimmunity, and vascular perturbations. Understanding these immunological mechanisms is essential for guiding clinical management and therapeutic strategies. Methods: We conducted a narrative review of peer-reviewed human studies published between January 2020 and August 2025, using PubMed/Medline, Scopus, and Web of Science, supplemented by manual searches. Studies reporting immunological assessments in long COVID patients, recovered individuals, or healthy controls were included. Findings were extracted and synthesized thematically across six domains: humoral and cellular immunity, autoimmune signatures, proteomic/metabolic and vascular dysregulation, viral persistence, complement/coagulation/thromboinflammation, and pediatric long COVID. Results: Long COVID is characterized by persistent low-grade inflammation, T- and B-cell dysregulation, and prolonged adaptive immune activation. Humoral responses remain elevated, while T-cell exhaustion and loss of coordination between immune compartments are common. Autoimmune phenomena, including latent and polyautoimmunity targeting cytokines, thyroid antigens, and interferons, are frequently observed. Proteomic, metabolic, and vascular perturbations, complement activation, and thromboinflammatory processes contribute to ongoing symptoms. Viral persistence and early immune biomarkers predict long COVID development. These immune alterations correlate with fatigue, cognitive impairment, respiratory dysfunction, and reduced quality of life in both adults and children. Conclusion: SARS-CoV-2 infection leaves a lasting immunological footprint marked by chronic inflammation, adaptive immune dysregulation, autoimmunity, and vascular perturbations. Integrating longitudinal immune assessments, biomarker profiling, and early predictive markers is critical for identifying high-risk individuals and informing interventions to reduce long COVID morbidity.
Abera et al. (2026) studied this question.