Background: Cognitive impairment is one of the most persistent and debilitating symptoms of Long COVID characterised by deficits in attention, working memory, and executive function, with profound impacts on quality of life and social participation. Mounting evidence links gut microbiome disturbance, systemic inflammation, and altered gut–brain signalling through the gut-brain axis to cognitive symptoms in Long COVID. Probiotics can be effective in modulating the gut microbiome and neuroimmune interactions enhancing cognitive function. This double-blind, placebo-controlled trial investigated whether a probiotic intervention had any effect on cognitive function in individuals with Long COVID, with outcomes assessed using the Paired Associates Learning Test of Executive Attention (PALTEA) and Stockings of Cambridge (SOC) tests of the CANTAB digital platform.
Methods: Adults with a diagnosis of Long COVID were recruited into the trial. Participants were assigned in equal groups to receive either a multi-strain probiotic (Symprove) or placebo for 12 weeks. Baseline demographics, medical history, and symptom prevalence were recorded. Cognitive functions were measured at baseline and 12 weeks using PALTEA and SOC. PALTEA provides a sensitive measure of memory and executive functioning, while SOC assesses spatial planning and problem-solving. Additional exploratory measures included fatigue severity (FACIT-F), gut symptoms (Gastrointestinal Symptom Rating Scale) and healthrelated quality of life (EQ-5D-5L). Between-group differences were analysed using independent-samples t-tests. Associations between cognitive tests and symptom scores were explored using Pearson correlation coefficients.
Results: Thirty-nine participants completed the trial (21 in the placebo group and 18 in the probiotic group). Preliminary analyses indicate that participants receiving probiotics demonstrated significant improvement in PALTEA performance from baseline to 12 weeks compared to the placebo group (p<0.05), with enhanced accuracy and reduced error rates across learning and recall trials. These changes suggest improved executive functioning and memory consolidation. SOC scores also increased in the probiotic group (p<0.01), indicating improved spatial planning and problem-solving. Improvements in PALTEA and SOC correlated with changes in gut symptom scores including reflux and indigestion. No serious adverse events were reported, and compliance with the probiotic regimen exceeded 90%.
Conclusion: These findings provide evidence that targeted probiotic supplementation can significantly improve aspects of cognition in people living with Long COVID. The results support the hypothesis that modulation of microbiome with probiotics in people with Long COVID translates into cognitive benefits. Probiotics may exert these benefits by restoring microbial diversity, attenuating systemic inflammation, enhancing short-chain fatty acid production, and modulating vagal signalling pathways relevant to memory and attention. Further work is underway using 16S sequencing to identify changes in the microbiome associated with improvements in cognitive function in the study participants. Probiotics are a biologically plausible intervention for cognitive dysfunction in Long COVID. This study contributes to the emerging field of microbiome-targeted therapies for Long COVID. Larger trials are warranted to confirm efficacy, identify optimal strains and dosing, and explore the durability of cognitive improvements.
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