Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), is a complex, multisystem condition that persists beyond the acute phase of COVID-19. It affects millions worldwide and presents with fatigue, cognitive impairment, autonomic dysfunction, respiratory difficulties, and a range of neurological, vascular, and metabolic disturbances. Despite its impact, the underlying virological and host-driven mechanisms remain incompletely defined, including the roles of viral persistence and tissue reservoirs, chronic immune activation, neuroinflammation, endothelial and coagulation abnormalities, autonomic and mitochondrial dysfunction, and disrupted metabolic and microbiome pathways.

Recent work has started to outline mechanistic endotypes, identify candidate biomarkers, refine diagnostic criteria, and test targeted interventions such as antivirals, immunomodulators, and vascular or metabolic therapies. However, linking these pathways to clear clinical phenotypes and treatment responses remains a major challenge. Harmonized case definitions, validated, mechanistically informed biomarkers, and rigorous clinical evaluations are urgently needed.

This Research Topic aims to advance mechanistic and translational research in Long COVID by integrating virological and host-response studies with precision diagnostics and targeted preventive and therapeutic strategies. We seek robust, reproducible science that connects mechanism to patient outcomes, refines mechanistically grounded phenotypes, and supports sustainable models of care and health policy. We encourage open science practices and patient-partnered approaches.

The scope includes original multidisciplinary research, clinical investigations, and translational studies in adults or children with post-acute SARS-CoV-2 sequelae, with a clear link between mechanistic insight and clinical relevance. We welcome work on:
- Viral persistence, tissue reservoirs, and pathophysiological mechanisms of Long COVID

- Immune dysregulation, neuroinflammation, and metabolic reprogramming in Long COVID

- Precision diagnostics: biomarkers, deep phenotyping, and harmonized clinical case definitions

- Mechanism-based therapeutic strategies, including antivirals, immunomodulators, rehabilitation protocols, and microbiome-targeted interventions

- Adaptive and pragmatic clinical trial designs to evaluate Long COVID interventions across clinical phenotypes

- Translational pipelines linking mechanistic insights to clinical outcomes, patient trajectories, and models of Long COVID care

Appendix: The Research Topic welcomes original research, reviews, meta-analyses, data reports, clinical case studies, policy analyses, and perspectives aligned with its scope.

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Long COVID: From Understanding to Recovery