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Review
. 2025 Apr;155(4):1059-1070.
doi: 10.1016/j.jaci.2024.12.1074. Epub 2024 Dec 24.

Long COVID: Pathophysiology, current concepts, and future directions

Chrysanthi Skevaki  1 , Charalampos D Moschopoulos  2 , Paraskevi C Fragkou  3 , Karsten Grote  4 , Elisabeth Schieffer  4 , Bernhard Schieffer  4
Affiliations
Review

Long COVID: Pathophysiology, current concepts, and future directions

Chrysanthi Skevaki et al. J Allergy Clin Immunol. 2025 Apr.

Abstract

Long COVID, an umbrella term referring to a variety of symptoms and clinical presentations that emerges in a subset of patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has a significant effect on quality of life and places a substantial burden on health care 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 perturbation, autoimmunity, latent virus 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 multiomics approaches. Further advances in understanding long COVID are needed to inform current and future therapeutics.

Keywords: COVID-19; SARS-CoV-2; endotypes; pathophysiology; persistence; postacute sequelae of COVID-19.

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Conflict of interest statement

Disclosure statement C.S. is supported by the Universities Giessen and Marburg Lung Center (UGMLC), the German Center for Lung Research (DZL), University Hospital Giessen and Marburg (UKGM) research funding according to article 2, section 3, cooperation agreement, and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)-SFB 1021 (project 197785619) and SK 317/1-1 (project 428518790), as well as by the Foundation for Pathobiochemistry and Molecular Diagnostics. Disclosure of potential conflict of interest: C. Skevaki reports consultancy and research funding from Bencard Allergie. The rest of the authors declare that they have no relevant conflicts of interest.