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INTRODUCTION - The Lingering Burden of COVID Relief
Since the emergence of COVID-19 in late 2019, the virus has left an undeniable mark on global health. According to the World Health Organisation, over 770 million people worldwide have been infected, with more than seven million lives lost to the disease¹. While some individuals experience only mild cold-like symptoms, others suffer from severe respiratory or systemic complications².
As vaccination campaigns have helped to control acute infections, another challenge has surfaced: Long COVID. Also referred to as post-COVID syndrome, this condition describes the persistence of symptoms weeks or even months after the virus has been cleared³. Current estimates suggest that Long COVID may affect 10–30% of COVID survivors, equating to at least 65 million individuals globally⁴ ⁵.
The symptoms of Long COVID are diverse and can significantly impair quality of life. Common issues include fatigue, memory losAs featured in The Lancet Infectious Diseases: A large-scale, randomised, double-blind, placebo-controlled clinical trials, difficulty concentrating, gastrointestinal upset, and general unwellness⁶. In the UK, Long COVID continues to put pressure on the NHS and public health systems, especially among working-age individuals.
Long COVID symptoms
In response, researchers are exploring novel approaches for COVID relief—including microbiome-targeted therapies such as long COVID probiotic formulas. Among them, a promising synbiotic preparation known as SIM01 has shown potential in restoring gut microbiome balance and reducing symptom severity.
Understanding Synbiotics - More Than Just Probiotics
Synbiotics, a combination of probiotics and prebiotics, offer more than what standalone probiotics can provide. While probiotics are live-friendly bacteria that support a balanced gut microbiome, prebiotics are the fibres that fuel their growth. Together, synbiotics work synergistically to enhance gut health and immune resilience.
During the COVID-19 pandemic, emerging studies highlighted the potential of microbiome-targeted strategies in supporting the immune system and reducing inflammation. Synbiotics (or COVID probiotics) may contribute to COVID relief by improving intestinal barrier function, modulating immune responses, and limiting pathogen invasion7. These findings have sparked interest in using synbiotic preparations not only for infection prevention, during active infection, but also in recovery phases where immune and gut health remain compromised. Among various potential gut-focused therapies, synbiotics stand out as a potential and well-tolerated approach.
SIM01 – A Clinically Developed Synbiotic Preparation
During the peak of the COVID-19 pandemic, researchers observed that patients with severe symptoms often displayed clear signs of gut microbiome disruption—marked by reduced beneficial bacteria and an overgrowth of harmful species8. Using cutting-edge metagenomics, AI-driven analysis, and big data from faecal samples, scientists compared the gut microbial profiles of hospitalised COVID-19 patients with those of healthy individuals. They identified a set of health-associated bacteria that were consistently more abundant in the healthy group.
From this group, three food-grade probiotic strains were carefully selected—strains with a well-established safety record and clinically validated health benefits ⁹. These were combined with three complementary prebiotics and encapsulated using a world-patented Italian microencapsulation technology (WO2013114185A1), designed to ensure the bacteria survive gastric acid and reach the colon alive for optimal colonisation.
In a hospital-based clinical study, COVID-19 patients receiving SIM01 alongside standard treatment recovered more rapidly than those on medication alone. Within two weeks, they experienced greater symptom relief, significantly lower inflammatory markers, improved antibody responses, and full resolution of gastrointestinal symptoms such as diarrhoea and abdominal pain ¹⁰.
These promising results laid the foundation for further research into SIM01’s therapeutic potential as long COVID probiotics beyond acute infection recovery.
The Landmark Clinical Study in The Lancet Infectious Diseases
To rigorously evaluate SIM01’s therapeutic potential as a COVID relief or long COVID probiotics in managing Long COVID, a landmark randomised, double-blind, placebo-controlled clinical trial was conducted and published in The Lancet Infectious Diseases in March 2024¹¹. This large-scale trial aimed to investigate whether restoring gut microbiota with a synbiotic formulation could alleviate the persistent symptoms associated with post-acute COVID-19 syndrome (PACS).
The study enrolled 463 adults suffering from PACS—defined as the presence of one or more persistent symptoms beyond four weeks after SARS-CoV-2 infection. Participants were randomly assigned to receive either the SIM01 synbiotic formula or a placebo (vitamin C), twice daily, over a period of six months. The SIM01 group received a microencapsulated SIM01 synbiotic preparation combination of three Bifidobacterium strains (B. adolescentis, B. bifidum, and B. longum) and three prebiotics.
Symptom improvement was measured using the PACSQ-14 questionnaire, a validated tool assessing 14 common Long COVID symptoms, including fatigue, memory loss, difficulty in concentration, gastrointestinal discomfort, and general unwellness. A positive response was defined as improvement in at least two symptoms, deemed sufficient by the participant to resume normal daily activities.
At six months, a significantly higher proportion of participants in the SIM01 group (60.5%) reported clinically meaningful symptom relief compared to the placebo group (41.5%). Notably, SIM01 intake was associated with marked improvements in five of the most burdensome symptoms: fatigue, memory loss, concentration difficulties, gastrointestinal upset, and general unwellness.
1. Digestive problems
SIM01 group had significantly higher proportion of subjects with improved symptoms
2. Fatigue
SIM01 group had significantly higher proportion subjects with improved symptoms
3. Difficulty in concentration
SIM01 group had significantly higher proportion subjects with improved symptoms
4. Memory problem
SIM01 group had significantly higher proportion subjects with improved symptoms
5. General Unwellness
SIM01 group had significantly higher proportion subjects with improved symptoms
The formulation was also well tolerated, with similar rates of mild and transient adverse events observed in both groups.
This clinical trial provides high-quality evidence that SIM01 synbiotic preparation (as a COVID relief or long COVID probiotics) can effectively reduce the symptom burden of Long COVID and supports its role as a potential microbiome-targeted intervention.
Why Gut Health Matters in COVID Recovery
The trial’s findings extend beyond symptom improvement, offering compelling evidence that gut microbiome restoration may play a key role in the recovery from Long COVID¹¹. Prior observational studies had already shown that both acute and post-acute COVID-19 infections are associated with significant gut dysbiosis—characterised by reduced microbial diversity, diminished abundance of beneficial bacteria, and an overrepresentation of pathogenic taxa.
At baseline, participants exhibited low levels of short-chain fatty acid (SCFA)-producing bacteria and a high abundance of potential pathogens such as Klebsiella pneumoniae, K. variicola, Parabacteroides merdae, and Ruminococcus gnavus. These microbial features are known to contribute to inflammation and impaired immune regulation.
After six months of SIM01 long COVID probiotics and prebiotics supplementation, metagenomic analysis revealed a significant restoration of microbial diversity and function. There was a notable increase in both the administered probiotic strains and other beneficial taxa, including Bifidobacterium pseudocatenulatum, Roseburia intestinalis, Roseburia hominis, Faecalibacterium prausnitzii, and Akkermansia muciniphila. Concurrently, the relative abundance of harmful bacteria and antimicrobial resistance genes declined.
Figure: Species-level gut microbiome differences between SIM01 and placebo groups at 6 months
Faecal microbiome composition at species level in participants receiving SIM01 versus placebo after six months, analysed using MaAsLin2. A false discovery rate (FDR) below 0.05 was considered statistically significant.
Red dots indicate bacterial species significantly enriched in the SIM01 group, while blue dots highlight species enriched in the placebo group.
Importantly, microbial functional pathways related to SCFA biosynthesis were significantly upregulated in the SIM01long COVID probiotics and COVID relief group. This metabolic shift suggests enhanced production of butyrate and acetate, key metabolites involved in immune modulation, gut barrier integrity, and energy metabolism.
Correlation analyses conducted in the study further demonstrated that increases in specific bacterial species were associated with symptom improvement. For example, a rise in B. adolescentis correlated with reductions in fatigue, memory loss, and gastrointestinal discomfort; B. bifidum was linked to improvements in fatigue and general unwellness; and B. longum was associated with better concentration.
These findings not only reinforce the link between gut health and systemic recovery but also support the biological plausibility that modulating the gut microbiota through targeted synbiotic supplementation, as long COVID probiotics or COVID relief, can play a central role in alleviating Long COVID symptoms.
Bringing It All Together
In this article, we explored how Long COVID continues to impact millions worldwide and introduced the concept of synbiotics as a targeted approach, as long COVID probiotics or COVID relief, to support gut health and recovery. We also looked at the development of SIM01—a clinically designed synbiotic formula based on research into microbiome imbalances observed in patients with COVID-19.
Building on these foundations, a large-scale clinical trial published in The Lancet Infectious Diseases investigated the potential of SIM01 to relieve persistent Long COVID symptoms. Over six months, individuals who took SIM01 long COVID probiotics (a synbiotic preparation combining patented-encapsulated probiotics and prebiotics) reported greater improvements in fatigue, memory loss, gastrointestinal discomfort, and poor concentration compared with those who received a placebo.
The study also observed notable shifts in the participants’ gut microbiota, including restored microbial diversity and an increase in beneficial species. But how did supplementing with just three specific probiotic strains lead to a broader improvement, boosting the growth of other native beneficial bacteria? The answer, as the research suggests, lies in the intelligent design of the synbiotic formula and a fascinating ecological process known as cross-feeding.
This mechanism works like a collaborative relay race within your gut. The prebiotics included in the SIM01 formula act as the initial fuel, specifically nourishing the three introduced Bifidobacterium strains. As these probiotics consume the prebiotics, they produce beneficial compounds, such as acetate and lactate. These compounds then become the perfect food source for other crucial native bacteria, like Faecalibacterium prausnitzii—a key producer of butyrate, a short-chain fatty acid vital for gut and immune health. In essence, the supplemented probiotics don’t just work alone; they kickstart a positive chain reaction, feeding and revitalising the resident beneficial bacteria and enhancing the entire ecosystem.
This finding reveals that our gut is not a passive container but a dynamic, interactive system. Effective microbiome support is not merely about adding good bacteria, but about fostering an environment where they can work together and thrive collectively. While more studies are needed, this research offers encouraging insight into how targeted gut microbiome support may play a pivotal role in recovery from Long COVID—and suggests that our gut health is more intricately connected to our systemic recovery than we ever understood.
References
-
World Health Organization (WHO) [Internet]. WHO Coronavirus (COVID-19) Dashboard. Geneva: WHO; 2023 [cited 2025 Apr 17]. Available from: https://covid19.who.int/
-
Nalbandian A, Sehgal K, Gupta A, et al. Post-acute COVID-19 syndrome. Nat Med. 2021;27(4):601–15.
-
Centers for Disease Control and Prevention (CDC) [Internet]. Post-COVID conditions: information for healthcare providers. Atlanta (GA): CDC; 2023 [cited 2025 Apr 17]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/post-covid-conditions.html
-
Davis HE, McCorkell L, Vogel JM, Topol EJ. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol. 2023;21(3):133–46.
-
Zhang F, Lau RI, Liu Q, Su Q, Chan FKL, Ng SC. Gut microbiota in COVID-19: key microbial changes, potential mechanisms and clinical applications. Nat Rev Gastroenterol Hepatol. 2023;20(5):323–37.
-
National Health Service (NHS) [Internet]. Long-term effects of coronavirus (Long COVID). London: NHS England; 2023 [cited 2025 Apr 17]. Available from: https://www.nhs.uk/conditions/covid-19/long-term-effects-of-covid-19-long-covid/
-
Hu J, Zhang L, Lin W, Tang W, Chan FKL, Ng SC. Review article: Probiotics, prebiotics and dietary approaches during COVID-19 pandemic. Aliment Pharmacol Ther. 2022;55(3):300-316. doi:10.1111/apt.16750.
-
Zuo T, Zhang F, Lui GCY, Yeoh YK, Li AYL, Zhan H, et al. Alterations in gut microbiota of patients with COVID-19 during time of hospitalisation. Gastroenterology. 2020 Sep;159(3):944–955.e8. doi:10.1053/j.gastro.2020.05.048
-
Yeoh YK, Zuo T, Lui GCY, Zhang F, Liu Q, Li AYL, et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut. 2021 Apr;70(4):698–706. doi:10.1136/gutjnl-2020-323020
-
Zuo T, Liu Q, Zhang F, Lui GCY, Tso EYK, Yeoh YK, et al. Depicting SARS-CoV-2 faecal viral activity in association with gut microbiota composition in patients with COVID-19. Gut. 2021 Feb;70(2):276–284. doi:10.1136/gutjnl-2020-322294
-
Lau RI, Su Q, Lau ISF, Ching JYL, Wong MCS, Lau LHS, et al. A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2024 Mar;24(3):256–65. doi:10.1016/S1473-3099(23)00685-0
