Effects of a multispecies probiotic intake on the recovery of patients with post-acute COVID-19 symptoms; a randomized, double-blind, placebo-controlled pilot trial

The gut-liver axis could be a potential therapeutic target for improving post-acute COVID-19 symptoms, and probiotics have been proposed as possible modulators. A pilot trial was conducted on patients who previously suffered from severe COVID-19 disease to explore the influence of microbiome modulation on a large panel of biomarkers related to the gut-liver axis in post-acute COVID-19 disease. 26 patients after severe COVID-19 infection were randomized into probiotic (Pro-Vi 5, Institut Allergosan, Graz, Austria) and placebo groups in a ratio of 1:1. 8 patients (45-65 years old, 38% female, 62% male) in the probiotic and 13 patients (43-63 years old, 39% female, 61% male) in the placebo group completed the study. Patients received the probiotic mixture or placebo twice a day for 6 months. At baseline, probiotic and placebo allocated patients did not differ. The probiotic group showed significant changes in several biomarkers compared to the placebo group. Maximum expiratory flow at 25% improved after 3 months (p=0.041), and vital capacity showed a statistical trend towards improvement after 6 months (p=0.055). Neutrophil ROS production decreased after 3 months in response to fMLF, E. coli, and PMA (p=0.033, p=0.01, p=0.034 respectively). The microbial richness also improved after 3 (p=0.047) and 6 months (p=0.014). Serum metabolome analysis showed differences in lipoprotein concentrations and distributions, primarily the triglyceride content of HDL-1 and LDL-2 increased (p=0.057, p=0.0017 respectively) after 6 months. HDL-4 was reduced after 3 months (p<0.0001) and increased to the baseline after 6 months. The LDL-2-triglycerides / HDL-4-phospholipids ratio increased after 3 months (p=0.001) and normalized after 6 months. In stool two microbial metabolites, 3,4-Dihydroxybenzeneacetic acid (p=0.015) and butyric acid (p=0.024) increased after 6 months in the probiotic group. The study provides preliminary evidence that probiotics can modulate clinical and laboratory biomarkers of the gut-liver axis related to post-acute COVID-19 disease.