Long-COVID - pathophysiology, current concepts and future directions.

Long-COVID, an umbrella term referring to a variety of symptoms and clinical presentations, which emerge in a subset of patients after SARS-CoV-2 infection, has a significant impact on an individual's quality of life and places a substantial burden on healthcare systems worldwide, straining financial and human resources. The pathophysiology of long-COVID remains incompletely understood, though several hypotheses have been proposed to explain different aspects of this complex condition. SARS-CoV-2 persistence, direct organ damage, innate and adaptive immune system pertubation, autoimmunity, latent viruses reactivation, endothelial dysfunction, and microbiome disturbances are among the most relevant avenues for elucidating the evolution, complexity, and mechanisms of long-COVID. Active investigation regarding potential biomarkers for long-COVID and its associated disease endotypes highlights the role of inflammatory mediators, immunophenotyping and multi-omics approaches. Further advances in understanding long-COVID are needed to inform current and future therapeutics.