Elevated Atherogenicity in Long COVID: A Systematic Review and Meta-Analysis

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Abstract

Background

Long COVID (LC) is a complex, multi-organ syndrome that persists following recovery from the acute phase of coronavirus infection. Cardiovascular involvement is frequently reported in LC, often accompanied by a spectrum of related symptoms. Dysregulated lipid profiles and elevated atherogenic indices have been implicated in LC, yet no comprehensive systematic review and meta-analysis has specifically addressed these biomarkers.

Objective

This study aims to systematically evaluate atherogenic indices and lipid-related biomarkers in individuals with LC compared to healthy controls.

Methods

A systematic search was conducted in databases including PubMed, Google Scholar, SCOPUS, and SciFinder from September to November 2024. Eligible studies reported lipid biomarker data for LC patients and controls, yielding 44 studies encompassing 8,114 participants (3,353 LC patients and 4,761 controls).

Results

LC patients exhibited significant elevations in Castelli Risk Indexes 1 (standardized mean difference, SMD = 0.199; 95% confidence intervals, CI: 0.087–0.312) and 2 (SMD = 0.202; 95% CI: 0.087–0.318). Atherogenic ratios, including triglyceride (TG)/high-density lipoprotein (HDL) (SMD = 0.294; 95% CI: 0.155–0.433), (TG + low-density lipoprotein, LDL + very low-density lipoprotein, VLDL)/(HDL + apolipoprotein, ApoA) (SMD = 0.264; 95% CI: 0.145–0.383), and ApoB/ApoA (SMD = 0.515; 95% CI: 0.233–0.796), were also significantly elevated. Additionally, LC patients demonstrated increased levels of LDL, total cholesterol, triglycerides, and ApoB, alongside reduced HDL and ApoA levels. Results were free from publication bias.

Conclusion

LC is associated with a pro-atherogenic lipid profile, marked by increased atherogenic components and decreased protective lipid biomarkers. These findings highlight a potential heightened risk for cardiovascular complications in LC patients, warranting further clinical and mechanistic investigations.

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