Proportion of PACS symptom reduction within six months. Credit: Lancet infectious diseases (2023). DOI: 10.1016/S1473-3099(23)00685-0
A randomized controlled trial conducted in Hong Kong finds that the symbiotic drug SIM01 relieves several symptoms of long COVID or post-acute COVID-19 syndrome (PACS).
SIM01 contains strains of anaerobic Bifidobacterium bacteria (which are probiotics) and soluble fiber (prebiotics) to alter the gut microbiome and possibly modify the immune response.
Twice daily doses
From June 2021 to August 2022, researchers at the Chinese University of Hong Kong randomly assigned 463 adult long-COVID patients at a single hospital in a 1:1 ratio to receive SIM01 or a vitamin C placebo by oral twice a day for six months. The median interval between infection and random assignment was four months.
Investigators clinically assessed participants at baseline for symptoms, quality of life, and physical activity level. At six months, investigators administered a 14-item symptom questionnaire to participants and collected blood and fecal samples to assess changes in the gut microbiome and blood cytokines (small proteins that trigger the immune response). .
“The decreased abundance of short-chain fatty acid-producing bacteria in the gut of COVID-19 patients could represent one of the crucial mechanisms contributing to the gut-lung interaction and thus the severity of disease in COVID-19,” the researchers wrote.
The study was published on December 7 in Lancet infectious diseases.
No effect on quality of life, exercise capacity
Nearly a third of patients (31%) had been hospitalized during their infections. At six months, significantly higher proportions of the SIM01 group reported improvement in fatigue (odds ratio (OR), 2.27), memory loss (OR, 1.97), difficulty concentrating (OR), , 2.64), gastrointestinal disorders (OR, 2.00), and general malaise (OR: 2.36) than the placebo group.
The increases in relative benefit after SIM01 treatment were 47% for fatigue, 56% for memory loss, 62% for difficulty concentrating, 30% for gastrointestinal complaints, and 31% for general malaise.
Rates of adverse events were similar between the two groups (SIM01, 10% versus placebo, 11%), and none were considered treatment-related. Receipt of SIM01, infection with omicron subvariants, vaccination before COVID-19 infection, and mild COVID-19 infection were predictors of symptom improvement.
Mean visual analog quality of life scores (on a scale of 0 to 100) at six months were not significantly different (76.0 for SIM01 recipients versus 74.5 for the placebo group). There was also no significant difference in physical activity at six months, per total metabolic equivalent of task minutes per week (median SIM01, 1,646.3 versus placebo, 1,902.0).
Symptom relief linked to certain microbiome changes
Fecal metagenomic analyzes showed that the gut microbiome was more diverse, including more short-chain acid-producing bacteria and fewer genes linked to antibiotic resistance, at six months than at baseline in SIM01 recipients, but not in the placebo group.
Correlating microbial changes with symptoms showed that relief of specific symptoms was linked to distinct changes in microbiome composition and functionality.
“For example, Bifidobacterium adolescentis showed positive correlations with reduction of fatigue, gastrointestinal disorders and memory loss,” the researchers wrote. “We also found that reduction in fatigue and general malaise correlated with high relative abundance of Bifidobacterium bifidum, while reduction in difficulty concentrating correlated with positive change in Bifidobacterium longum.”
Cytokine analyzes yielded no significant results.
“Treatment with SIM01 alleviates several symptoms of PACS,” they wrote. “Our results have implications for the management of PACS through modulation of the gut microbiome. Further studies are needed to explore the beneficial effects of SIM01 in other chronic or post-infectious conditions. »
Lack of a universal tool for assessing long COVID symptoms
In a related commentary, Betty Raman, DPhil, and Maheshi Ramasamy, DPhil, both of the University of Oxford, said new evidence highlights the importance of the gut microbiome in the development of long COVID, with disruption of microbial balance, or gut dysbiosis, in some patients.
“There are now several studies showing that probiotics, made up of beneficial bacteria such as Lactobacillus and Bifidobacterium species, may improve gut health, modulate inflammation, and improve immune function,” they wrote.
But limitations of the study, such as the lack of a long, universally accepted COVID symptom assessment tool and reliance on subjective reporting of symptoms, complicate interpretation of the results.
“Although some improvement in PACS symptoms was observed, this did not correspond to measurable improvements in quality of life or physical activity after six months, suggesting that the real benefits of treatment on General health perception and functional capacity may be low.” Raman and Ramasamy wrote.
More information:
Raphaela I Lau et al, A symbiotic preparation (SIM01) for post-acute syndrome of COVID-19 in Hong Kong (RECOVERY): a randomized, double-blind, placebo-controlled trial, Lancet infectious diseases (2023). DOI: 10.1016/S1473-3099(23)00685-0
Betty Raman et al, Synbiotics in post-acute COVID-19 syndrome: a potential new treatment framework?, Lancet infectious diseases (2023). DOI: 10.1016/S1473-3099(23)00735-1
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Quote: Investigational drug that alters gut microbiome shows promise for prolonged COVID relief (December 29, 2023) retrieved December 29, 2023 from
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