Background
Long COVID (LC) is characterized by recurrent, prolonged, and new symptoms of COVID-19 at least 3 months after a SARS-COV-2 infection. LC was associated with fungal translocation, gut dysfunction, and enhanced inflammation. The anti-inflammatory vitamins K2/D3 were previously shown to reduce inflammation and help attenuate the course of acute COVID infection. This trial aims to investigate the effects of Vitamins K2/D3 on LC symptoms, gut markers and inflammatory markers in people with established long COVID.
Methods
This single-site randomized-controlled enrolled adults experiencing ≥2 moderate long COVID symptoms at least 3 months after COVID-19 infection. The RECOVER Long COVID index (JAMA 2023), number of LC symptoms, and resolution of symptoms were considered. Participants were randomized 2:1 to daily 240 µg K2 (pure MK-7 form) and 2000 UI Vitamin D3 or standard of care (SOC) for 24 weeks. Co-primary endpoints were changes in symptomatology and in select inflammatory markers at 24 weeks.
Results
We enrolled 151 participants (n=98 received vit K2/D3 and 53 standard of care). The median age was 46 years, 71% female and 29% non-white. Baseline demographics were balanced between groups. At 24 weeks, the active treatment group had a sharp increase in 25(OH) D indicating good treatment adherence, without change in the control arm. Vitamins K2/D3 arm showed a 3.2 (P=0.04) reduction in LC Index (P=0.04) and nearly two less (△ = -1.7; P=0.02) total number of LC symptoms compared to the SOC arm. Additionally, larger reductions in oxidized LDL, sTNF-RI, CD163, and the fungal translocation marker (1, 3)-β-d-glucan (BDG) were observed in the vitamins K2/D3 arm compared to the SOC arm (P<0.01). In adjusted models, vitamins K2/D3 randomization was associated with decreases in LC Index, but decreases in inflammatory markers and BDG were not. Decreases in BDG were associated with K2/D3 randomization and with decreases in inflammatory markers.
Conclusions
Vitamins K2/D3 improved Long COVID Index, number of LC symptoms, fungal translocation and several inflammatory markers. Vitamins K2/D3 provide a promising safe intervention for people suffering from long-COVID. Larger and longer studies are needed to assess the impact of this safe anti-inflammatory strategy.
Table or Figure
