Expression of Toll-like Receptor 7 and Toll-like Receptor 9 in COVID-19 Patients and Their Association with Disease Severity

Abstract

Toll-like receptors (TLRs) play an important role in innate immunity, mediating viral recognition, antiviral responses, and cytokine production. This study evaluated TLR7 and TLR9 expression levels in COVID-19 patients and their associations with COVID-19 infection and disease severity. A total of 134 adults were included: 94 COVID-19 patients and 40 controls. RT-PCR confirmed SARS-CoV-2 infection; TLR7 and TLR9 expression levels were determined by quantitative real-time PCR. Participants’ clinical characteristics and laboratory findings were evaluated. TLR7 and TLR9 expression levels were significantly higher in COVID-19 patients than in controls (both p < 0.001). Both markers were independently associated with COVID-19 infection by multivariate analysis (OR: 6996.516, p < 0.001; OR: 7.365, p = 0.004) and showed excellent discriminatory performance by ROC analysis (AUC: 0.973 and 0.937, both p < 0.001). Among COVID-19 patients, TLR9 expression and ALT were independently associated with moderate-to-critical disease (OR: 1.448, p = 0.030; OR: 1.092, p = 0.032). TLR9 expression and ALT showed modest discriminatory performance for distinguishing moderate-to-critical COVID-19 from mild disease (AUC: 0.623, p = 0.042; AUC: 0.641, p = 0.020, respectively), while the combined model demonstrated a slight improvement (AUC: 0.659, p = 0.008). TLR7 and TLR9 may represent potential biomarkers for distinguishing COVID-19 patients from controls, and TLR9 may provide additional information on disease severity. These findings need validation in larger, multicenter studies before clinical application.