Pathophysiological Mechanisms in Long COVID: A Mixed Method Systematic Review

Nawar Diar Bakerly (), Nikki Smith, Julie L. Darbyshire, Joseph Kwon, Emily Bullock, Sareeta Baley, Manoj Sivan and Brendan Delaney
Additional contact information
Nawar Diar Bakerly: Faculty of Science and Engineering, Manchester Metropolitan University, Manchester M15 6BH, UK
Nikki Smith: Locomotion Study Patient Advisory Group, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Level D, Martin Wing, Leeds General Infirmary, Leeds LS1 3EX, UK
Julie L. Darbyshire: Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford OX2 6GG, UK
Joseph Kwon: Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford OX2 6GG, UK
Emily Bullock: Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, UK
Sareeta Baley: Birmingham Community Healthcare NHS Trust, Birmingham B7 4BN, UK
Manoj Sivan: Rehabilitation Medicine, University of Leeds, Leeds Teaching Hospitals and Leeds Community Healthcare NHS Trusts, Leeds LS11 0DL, UK
Brendan Delaney: Medical Informatics and Decision Making, Imperial College, London SW7 2AZ, UK

IJERPH, 2024, vol. 21, issue 4, 1-23

Abstract: Introduction: Long COVID (LC) is a global public health crisis affecting more than 70 million people. There is emerging evidence of different pathophysiological mechanisms driving the wide array of symptoms in LC. Understanding the relationships between mechanisms and symptoms helps in guiding clinical management and identifying potential treatment targets. Methods: This was a mixed-methods systematic review with two stages: Stage one (Review 1) included only existing systematic reviews (meta-review) and Stage two (Review 2) was a review of all primary studies. The search strategy involved Medline, Embase, Emcare, and CINAHL databases to identify studies that described symptoms and pathophysiological mechanisms with statistical analysis and/or discussion of plausible causal relationships between mechanisms and symptoms. Only studies that included a control arm for comparison were included. Studies were assessed for quality using the National Heart, Lung, and Blood Institute quality assessment tools. Results: 19 systematic reviews were included in Review 1 and 46 primary studies in Review 2. Overall, the quality of reporting across the studies included in this second review was moderate to poor. The pathophysiological mechanisms with strong evidence were immune system dysregulation, cerebral hypoperfusion, and impaired gas transfer in the lungs. Other mechanisms with moderate to weak evidence were endothelial damage and hypercoagulation, mast cell activation, and auto-immunity to vascular receptors. Conclusions: LC is a complex condition affecting multiple organs with diverse clinical presentations (or traits) underpinned by multiple pathophysiological mechanisms. A ‘treatable trait’ approach may help identify certain groups and target specific interventions. Future research must include understanding the response to intervention based on these mechanism-based traits.

Keywords: long COVID; post COVID syndrome; pathophysiology; brain fog; fatigue; treatable trait (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2024
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