Effect of Lactoferrin treatment on symptoms and physical performance in Long-COVID patients: a randomized, double-blind, placebo controlled trial

Abstract

Long-COVID is a heterogeneous condition with a variety of symptoms which persist at least 3 months after SARS-CoV-2 infection with often profound impact on quality of life. Lactoferrin is an iron-binding glycoprotein with anti-inflammatory and anti-viral properties. Current hypothesises regarding long-COVID aetiology include ongoing immune activation, viral persistence, and auto-immune dysregulation. Therefore, we hypothesized that long-COVID patients may potentially benefit from lactoferrin treatment.To investigate the effect of lactoferrin on various long-COVID domains: fatigue, anxiety, depression, cognitive failure, and muscle strength.We performed a randomized, double-blind placebo-controlled trial in long-COVID patients aged 18–70 years within 12 months after proven SARS-CoV-2 infection. Patients were randomized (1:1) to 6 weeks lactoferrin (1200 mg daily) or placebo. At 3 hospital visits (T0, T6, and T12 weeks) patient reported outcome measures (PROMs) were collected, physical performance tests were performed, and blood was drawn. The difference in fatigue at T6 was the primary outcome.Seventy-two participants were randomized to lactoferrin (N=36) or placebo (N=36). We showed a significant decrease in fatigue between T0 and T6 in both study arms, but without significant difference between the study arms, respectively 3.9 [95% CI: 2.3–5.5] and 4.1 [95% CI: 2.3–5.9](p=0.007 and p=0.013). In none of the other outcomes a significant difference was found in favour of the lactoferrin arm at T6 or T12.Although both long-COVID arms showed improved clinical outcomes at T6, the improvement did not continue until T12. Lactoferrin provided no benefit in terms of fatigue, other PROMs or physical functioning.