Pathophysiological mechanisms in Long Covid: A mixed method systematic review

Abstract

Abstract Introduction Long COVID (LC) affects approximately 1.9 million people in the UK. Little is known about its pathophysiologies. Understanding links between LC pathophysiologies and symptoms could guide treatment decisions. Here we report a mixed methods review to identify potential treatment targets. Methods A two-stage review of LC publications was conducted using clear eligibility criteria, a structured search strategy, and quality assessment. Review 1 included review of systematic reviews published on LC symptoms and pathophysiologies until July 22; Review 2 included primary studies of LC symptoms and pathophysiologies published June 21-October 22. Results The quality of publications in both stages (Review 1 [19 reviews] and Review 2 [46 primary studies]), was moderate to poor. From these publications we identified links between LC symptoms and immune dysregulation (ILs 6 and 8), micro and macro vascular inflammation leading to endothelitis and microthrobitis, and humoral response affecting viral persistence. Some studies reported impaired gas transfer leading to respiratory system issues. Brain and cardiac abnormalities on imaging were also reported. Conclusions LC probably stems from multiple pathophysiologies with interlinked pathways. A ‘treatable trait’ approach may be appropriate. Gaps in evidence remain, including limited interventional trials in LC.