Immunomodulatory and anti-inflammatory effects of oleuropein-standardized olive leaf extract in viral infections: a randomized controlled pilot study

Abstract Background Despite advances in antiviral therapies, effective supportive treatments that reduce inflammation and enhance host immune responses remain an important unmet need in systemic viral infections such as COVID-19. Standardized Olive Leaf Extract (SOLE), rich in oleuropein, has demonstrated antiviral, anti-inflammatory, and immunomodulatory properties in preclinical studies. This pilot randomized clinical trial aimed to explore the potential role of SOLE as an adjunct to standard care, with particular emphasis on clinical symptoms and selected inflammatory and immune biomarkers in patients with mild to moderate COVID-19. Methods This randomized, double-blind, placebo-controlled pilot study enrolled adult patients with laboratory-confirmed mild to moderate COVID-19. Participants were randomly assigned (1:1) to receive either SOLE capsules (750 mg, standardized to 50% oleuropein; 375 mg oleuropein) or matching placebo twice daily for 10 days, in addition to standard treatment. Primary outcomes included viral clearance assessed by RT-PCR and changes in inflammatory and immune parameters, including lactate dehydrogenase (LDH) levels and lymphocyte count. Results A total of 49 patients completed the intervention period. No statistically significant difference in viral clearance was observed between the SOLE and placebo groups ( P = 0.296). However, preliminary data suggested that patients receiving SOLE tended toward earlier resolution of several clinical symptoms, including headache ( P = 0.001), dyspnea ( P < 0.001), and fever ( P = 0.01). In addition, SOLE supplementation was associated with a significant increase in lymphocyte count compared with placebo ( P = 0.002) and a significant reduction in LDH levels ( P = 0.038), suggesting a favorable immunomodulatory and anti-inflammatory effect. Conclusion In this pilot study, standardized olive leaf extract rich in oleuropein did not demonstrate a direct antiviral effect but was associated with meaningful improvement in clinical symptoms and modulation of key inflammatory and immune markers. These findings suggest that SOLE may serve as a supportive adjunctive therapy to alleviate the inflammatory and symptomatic burden of viral infections. Larger studies are warranted to confirm these preliminary observations and further clarify the clinical relevance of oleuropein-mediated immune modulation. Graphical abstract