Synbiotic formula shows promise in reducing long COVID symptoms

In a recent study published in the journal The Lancet Infectious Diseases, researchers investigated the efficacy of a novel synbiotic preparation named SIM01 against the symptoms of post-acute COVID-19 syndrome. They tested the formulation on a Hong Kong-based study cohort comprising 463 patients over the course of six months.

Their findings highlight that SIM01 supplementation significantly alleviated fatigue, bolstered memory, and improved concentration in these cases compared to the controls. Furthermore, general unwellness and gastrointestinal distress were significantly reduced in the cohort receiving SIM01.

This study marks one of the first steps in treating this hitherto prevalent yet poorly understood and untreatable condition. It may be the basis for future gut microbiota remedies for long COVID.

Study: A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial. Image Credit: Donkeyworx / Shutterstock

What is PACS?

The coronavirus disease 2019 (COVID-19) remains one of the worst pandemics in human history, directly infecting more than 772 million individuals and claiming almost 7 million lines globally. Unfortunately, surviving the infection was not the end of COVID-19-related misfortune, with between 10-30% of survivors retaining COVID-19 symptoms (or even developing new ones) for weeks, months, and, in rare cases, even years after recovering from the primary infection.

Colloquially named ‘long COVID’ the medical post-acute COVID-19 syndrome has been defined by the World Health Organization (WHO) and the US Centers for Disease Control and Prevention (CDC) as any COVID-19 symptoms that “persist beyond four weeks after the acute infection and could last for up to several years.”

Given the novelty of the condition, PACS remains poorly understood, albeit recent studies into the syndrome have identified that COVID-19 results in significant alternations to the composition and function of gut microbiota, which may play a critical role in PCAS.

“…metagenomic sequencing of fecal samples showed depletion of several beneficial bacteria, such as Bifidobacterium adolescentis, in association with specific PACS symptoms.”

PCAS has been responsible for globally extensive socioeconomic loss and remains a highly debilitating syndrome for patients living with the condition. Discovering a cure for the more than 65 million PCAS patients worldwide is imperative before human society can resume pre-COVID-19 stability and function.

About the study

In the present study, researchers conducted a randomized, double-masked, placebo-controlled trial to investigate the efficacy of SIM01, a novel synbiotic formulation designed to alleviate PACS symptoms. The study was carried out between 25 June 2021 and 12 August 2022 and included 463 patients randomly assigned to either the case (SIM01; n = 232) or control (placebo; n = 231) cohorts.

SIM01 consists of a micro-encapsulated powder (lyophilized) comprising 20 billion colony-forming units (CFUs) of Bifidobacterium bifidu, B. adolescentis, and B. longum. The formulation also contains prebiotic compounds (n = 3) and dextrin, which are known to promote probiotic growth. Previous data on the relative abundance of these components in healthy adult Chinese individuals was used to decide the relative concentrations of PACS constituents.

Study participants were COVID-19 survivors aged 18 or older with PACS symptoms. Participants lacking at least PACS symptoms were excluded from data analyses. The number of PACS symptoms and their relative severities was assessed using a post-acute COVID-19 syndrome 14-item improvement questionnaire (PACSQ-14). Study treatment involved cases and controls ingesting two sachets daily comprising either SIM01 (cases) or low-dosage vitamin C (controls).

Data collection included participant demographic information (especially sex and age), medical data (obtained from hospital records), and physical activity metrics. “quality of life and physical activity were assessed by the trained interviewers using a visual analog scale, with scores ranging from 0–100, and International Physical Activity Questionnaire.”

Renal function, liver function, and inflammatory marker profiling were achieved using blood plasma samples collected during initial screening and then again during follow-ups at 3 and 6 months. Fecal samples were further collected for microbiome profiling.

“An independent Data and Safety Monitoring Committee (DSMC) consisting of two physicians and a biostatistician regularly reviewed data on adverse events and monitored patient safety.”

Study findings

SIM01 treatment resulted in a host of beneficial outcomes, including alleviating gastrointestinal upset, a common symptom of PACS. The formulation was further found to result in a more than 2-fold reduction in fatigue when comparing case energy levels to their control counterparts. This outcome is most likely due to increased microbial butyrate production, a byproduct of the bacteria included in the formulation.

“The present study did not identify a significant difference in quality of life and physical activity between the two groups at six months.”

Surprisingly, SIM01 supplementation was associated with improvements in concentration and memory recall, two previously unexplored symptoms of Long COVID. The mechanisms underpinning these interactions remain unknown and should be the focus of future research aimed at alleviating this globally prevalent condition.

Written by

Hugo Francisco de Souza

Hugo Francisco de Souza is a scientific writer based in Bangalore, Karnataka, India. His academic passions lie in biogeography, evolutionary biology, and herpetology. He is currently pursuing his Ph.D. from the Centre for Ecological Sciences, Indian Institute of Science, where he studies the origins, dispersal, and speciation of wetland-associated snakes. Hugo has received, amongst others, the DST-INSPIRE fellowship for his doctoral research and the Gold Medal from Pondicherry University for academic excellence during his Masters. His research has been published in high-impact peer-reviewed journals, including PLOS Neglected Tropical Diseases and Systematic Biology. When not working or writing, Hugo can be found consuming copious amounts of anime and manga, composing and making music with his bass guitar, shredding trails on his MTB, playing video games (he prefers the term ‘gaming’), or tinkering with all things tech.