, Ahmed Issa AL-Tameemi2
, Zainab S Mahmood3
, Hula Y. Fadhil2
, Khalida.F AL-azawi4
Background and Aims: Severe influenza infections, particularly H1N1, are associated with dysregulated immune responses. Toll-like receptor 7 (TLR7) and the chemokine CCL2 (MCP-1) play crucial roles in viral recognition and inflammation, yet their relationship with disease severity remains unclear.
Materials and Methods: A case-control study was conducted between November–December 2023, enrolling 60 patients with influenza A (subtyped H1N1) and 30 age- and sex-matched controls. Patients were categorized into Influenza-like Illness (ILI) and Severe Acute Respiratory Infection (SARI) groups. TLR7 expression in blood samples was quantified by RT-qPCR, while serum CCL2 concentrations were measured by ELISA. Correlations with clinical parameters, including CRP, WBC, ferritin, diabetes, and demographic factors, were evaluated. ROC curve analysis was performed to assess biomarker predictive potential.
Results: TLR7 expression was significantly upregulated in H1N1 patients (median 8.6) compared with controls (median 1.6, p<0.001), with higher levels observed in SARI versus ILI patients (p=0.008). ROC analysis showed that TLR7 fold >3.85 predicted greater severity (AUC=0.751, sensitivity 76.1%, specificity 75.2%). Conversely, CCL2 concentrations were significantly lower in SARI patients (median 37.5 pg/mL) compared with ILI patients (87.4 pg/mL) and controls (86.8 pg/mL, p=0.001). ROC analysis indicated that CCL2 <76.3 pg/mL predicted disease progression (AUC=0.794, sensitivity 70.3%, specificity 67.6%). Positive correlations were found between TLR7 and CRP/WBC, while CCL2 correlated with CRP and ferritin. Diabetes was associated with altered biomarker expression.
Conclusion: TLR7 overexpression and reduced CCL2 levels reflect distinct but complementary immune mechanisms underlying severe influenza outcomes. Together, they may serve as a predictive biomarker panel for identifying patients at risk of SARI. Integration of molecular and protein biomarkers offers a more comprehensive diagnostic approach for influenza management.
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