Pidotimod Boosts Recovery and Lowers Complications in Unvaccinated Adults with Influenza

Background Influenza A and B continue to be major global causes of morbidity and mortality. Current antiviral and vaccine strategies are limited by viral variability and the narrow window for effective treatment. Pidotimod, a synthetic immunomodulatory dipeptide, enhances both innate and adaptive immune responses; however, its efficacy in adult influenza remains underexplored. Methods We conducted a retrospective observational study in Italy involving 66 unvaccinated adults (aged 18–65) with confirmed influenza A or B who had not received antiviral therapy. Participants received either symptomatic treatment alone (control group, n = 25) or symptomatic treatment plus oral Pidotimod 800 mg twice daily for 5–10 days (treatment group, n = 41). Primary outcomes included the number and persistence of influenza symptoms at 48 hours and 5 days. Secondary outcomes were the incidence of bacterial complications and antibiotic use. Results At 48 hours, fever persisted in 39% of the Pidotimod group compared to 60% of controls (p < 0.05); at 5 days, persistence rates were 0% vs. 20%, respectively (p < 0.001). Patients receiving Pidotimod reported significantly fewer symptoms overall at bothtime points (mean symptom count at 48h: 1.53 vs. 3.70, p = 0.021; at 5 days: p = 0.001), with marked reductions in nasal congestion (p = 0.003) and sore throat (p = 0.008). Bacterial complications occurred less frequently in the treatment group (p = 0.023). No serious adverse events related to Pidotimod were observed. Conclusions In adults with influenza A or B, Pidotimod was associated with faster symptom resolution and fewer bacterial complications, supporting its potential role as an adjunct immunomodulatory therapy. These findings warrant further validation through randomized controlled trials.