A triple‐blind, placebo‐controlled, randomized clinical trial to evaluate the effect of curcumin‐containing nanomicelles on cellular immune responses subtypes and clinical outcome in COVID‐19 patients

Triple-blind, placebo-controlled randomized clinical trial in COVID-19 patients at Shahid Mohammadi Hospital in Bandar Abbas, Iran. Twenty participants were randomized to the nano-curcumin arm in a 1:1 allocation with placebo, with outcomes assessed at days 0, 7, and 14.

Nano-curcumin was given as Sinacurcumin soft-gel capsules containing 40 mg curcuminoids nanomicelles per capsule, taken orally four times daily after breakfast, lunch, dinner, and before bedtime for 2 weeks. The active regimen was compared with placebo in a triple-blind randomized trial.

Nano-curcumin appeared to favorably modulate inflammatory and immune responses, but clear clinical symptom improvement was not demonstrated over 14 days. TBX21 mRNA decreased at days 7 and 14, with a significant between-group difference on day 7 (p=.0252; TBX21 day 7 p=.02), and FOXP3 increased with a significant day 7 between-group difference (p=.005). RORC was downregulated, IFN-γ was not significantly different, and IL-4, IL-17, and TGF-β changes were not significant between groups. Lymphocyte percentage was higher in the nano-curcumin arm, 5% vs 20% had CRP level more than +2 in week 2, no specific adverse reactions were observed, and clinical manifestations did not differ significantly between groups at 0, 7, or 14 days.

Small active-arm sample size, short 2-week treatment and follow-up, and several biomarker changes were not statistically significant. Clinical outcome differences were not significant, so the findings are mainly limited to immune-marker signals rather than clear patient-centered benefit. Single-center conduct in one hospital in Iran may limit generalizability.