Background: Long COVID (LC) is a heterogenous condition with persisting symptoms for at least 3 months. Lactoferrin (Lf) is an iron-binding glycoprotein and has anti-inflammatory and anti-viral properties. LC patients could potentially benefit from Lf treatment.

Aims: Investigate effect of Lf on fatigue, mental symptoms, muscle strength, and cognitive function in LC patients.

Methods: We performed a randomized, double-blind placebo-controlled trial in LC patients aged 18 ? 70 years within 12 months after a proven COVID-19 infection. Patients were randomized (1:1) to 6 weeks Lf (1200mg daily) or placebo, followed by 6 weeks without treatment. At 3 hospital visits (T0, T6 and T12), Fatigue Assessment Scale (FAS), Hospital Anxiety and Depression Scale (HADS), Cognitive Failures Questionnaire (CFQ), and muscle strength tests were performed.

Results: We showed a significant decrease in FAS score between T0 and T6 in both the Lf and control group, respectively 3.9 [95% CI 2.3-5.5] and 4.1 [95% CI 2.3-5.9] (p<0.001). A significant decrease was measured in HADS fear, HADS depression and CFQ between T0 and T6. Sit-stand test was significantly improved at T6. However, no significant difference was seen between Lf and placebo for any of the outcome parameters.

Conclusion: Although both LC groups improved, our study shows no difference between Lf and placebo in terms of fatigue, mental symptoms, and muscle strength after 6 and 12 weeks.