Post-COVID-19 Condition as a Mass Disabling Event: Unifying Pathophysiology, Clinical Phenotypes, and the

,, Bhagvanti; Yameen, Samira; Tasleem, Muhammad Wasim; Rajpoot, Sehrish Rana

doi:10.21608/ejpa.2025.408624.1091

Post-COVID-19 Condition as a Mass Disabling Event: Unifying Pathophysiology, Clinical Phenotypes, and the "Treatable Traits" Approach

Document Type : Review

Authors

¹ Department of Zoology, Federal Urdu University of Arts, Science and Technology (Gulshan-E- Iqbal Campus), Karachi

² Department of Physiology, University of Karachi

³ Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan.

⁴ University College of Conventional Medicine, Islamia University Bahawalpur, Pakistan

10.21608/ejpa.2025.408624.1091

Abstract

Background: Post-COVID-19 Condition (PCC), or Long COVID, affects 10-20% of SARS-CoV-2 survivors, emerging as a significant global health challenge and a mass disabling event due to its persistent and heterogeneous symptoms. We sought to synthesize current evidence on PCC’s pathophysiology, delineate its major clinical phenotypes, and propose a personalized treatment framework. Methods: A review of recent literature was conducted, focusing on pathophysiological mechanisms (viral persistence, immune dysregulation, endothelial dysfunction, neurological disruptions) and clinical phenotyping from large-scale studies like National Institutes of Health (NIH) RECOVER. Results: PCC exhibits profound clinical heterogeneity, with major phenotypes including fatigue-dominant, neurocognitive, cardiopulmonary, and dysautonomia-related clusters. Core pathophysiological pillars include viral persistence, immune dysregulation, endothelial dysfunction, and neurological disruptions. The proposed "treatable traits" model targets specific pathophysiological traits (e.g., micro thrombosis, mast cell activation) for personalized diagnostics and therapies. Conclusion: The "treatable traits" model offers a roadmap for shifting PCC management from symptomatic relief to mechanism-based care, guiding effective treatment and future research to address this global disability crisis.

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