Elevated levels of chemokine C-C motif ligand 5 (CCL5) are significantly associated with favorable outcomes and improved survival in patients suffering from respiratory viral infections, according to a systematic review and meta-analysis published in JAMA Network Open. Researchers evaluated studies published through October 1, 2025, to quantify how CCL5 concentrations correlate with disease severity and mortality across multiple viral pathogens.
Study Design and Patient Demographics
The systematic review incorporated 18 observational studies published between 2012 and 2024. These investigations collectively enrolled 2,376 unique patients with a median age of 58.2 years, of whom 60% were men. Investigators analyzed biologic samples to assess CCL5 levels and tracked clinical endpoints including unfavorable disease progression and mortality.
The viral etiologies identified across the study populations were diverse. Five studies focused on SARS-CoV-2, three examined respiratory syncytial virus (RSV), one investigated influenza A virus subtype H1N1, one evaluated a combination of RSV and rhinovirus, and one looked at nonspecific viral lower respiratory tract infections. Among these cohorts, 11 studies involving 1,214 patients evaluated unfavorable disease progression, while 7 studies involving 1,162 patients evaluated mortality outcomes.
Prognostic Value and Statistical Findings
Pooled analyses revealed that patients with elevated CCL5 levels experienced a reduced risk of unfavorable disease progression, showing an odds ratio (OR) of 0.78 with a 95% confidence interval ranging from 0.71 to 0.85. The protective association was even more pronounced regarding mortality, with an odds ratio of 0.65 (95% CI, 0.55–0.76). Statistical testing indicated that the protection conferred by elevated CCL5 was significantly greater against mortality than against unfavorable disease progression.
Subgroup analyses demonstrated consistent associations between increased CCL5 levels and protection against unfavorable disease progression, with no significant interaction found between coronavirus and noncoronavirus types, or between pediatric and adult age groups. Univariable metaregression analysis indicated that covariates such as study publication year, country income status, and sample size did not significantly modify the protective effects of the chemokine.
Model Adjustments and Limitations
Sensitivity analyses addressed underlying heterogeneity within the data. For unfavorable disease progression, the protective effect of elevated CCL5 remained significant in unadjusted models with an odds ratio of 0.77, but lost statistical significance in multivariable-adjusted models where the odds ratio shifted to 0.94. Conversely, the protective association against mortality persisted across both unadjusted models (OR, 0.64) and multivariable-adjusted models (OR, 0.70).
The study authors noted several limitations, including the small number of studies available for certain subgroup evaluations, variations in laboratory assay techniques used to measure CCL5, differing clinical definitions of disease severity, and the reliance on observational data and pooled heterogeneous measures.
Clinical Implications and Biomarker Potential
The research team concluded that CCL5 holds notable potential as a prognostic biomarker for patient stratification during respiratory viral infections. The findings support the active investigation of therapeutic strategies designed to boost CCL5 responses in patients who demonstrate clinical deficiencies in this specific chemokine.
Worth a look