A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial
MSc Raphaela I Lau, PhD, I S F Qi Su, Ivan S F Lau, Jessica Y L Ching, Martin C S Wong, Louis H S Lau, Hein M Tun, Chris K P Mok, Steven W H Chau, Yee Kit Tse, Chun Pan Cheung, Giann Moses K T Li, Giann T Y Yeung, Pui Kuan Cheong, Prof F K L Francis K L Chan, Siew C Ng
The Lancet Infectious Diseases, doi:10.1016/s1473-3099(23)00685-0
Background Post-acute COVID-19 syndrome (PACS) affects over 65 million individuals worldwide but treatment options are scarce. We aimed to assess a synbiotic preparation (SIM01) for the alleviation of PACS symptoms.
Methods In this randomised, double-blind, placebo-controlled trial at a tertiary referral centre in Hong Kong, patients with PACS according to the US Centers for Disease Control and Prevention criteria were randomly assigned (1:1) by random permuted blocks to receive SIM01 (10 billion colony-forming units in sachets twice daily) or placebo orally for 6 months. Inclusion criterion was the presence of at least one of 14 PACS symptoms for 4 weeks or more after confirmed SARS-CoV-2 infection, including fatigue, memory loss, difficulty in concentration, insomnia, mood disturbance, hair loss, shortness of breath, coughing, inability to exercise, chest pain, muscle pain, joint pain, gastrointestinal upset, or general unwellness. Individuals were excluded if they were immunocompromised, were pregnant or breastfeeding, were unable to receive oral fluids, or if they had received gastrointestinal surgery in the 30 days before randomisation. Participants, care providers, and investigators were masked to group assignment. The primary outcome was alleviation of PACS symptoms by 6 months, assessed by an interviewer-administered 14-item questionnaire in the intention-to-treat population. Forward stepwise multivariable logistical regression was performed to identify predictors of symptom alleviation. The trial is registered with ClinicalTrials.gov, NCT04950803.
Findings Between June 25, 2021, and Aug 12, 2022, 463 patients were randomly assigned to receive SIM01 (n=232) or placebo (n=231). At 6 months, significantly higher proportions of the SIM01 group had alleviation of fatigue (OR 2•273, 95% CI 1•520-3•397, p=0•0001), memory loss (1•967, 1•271-3•044, p=0•0024), difficulty in concentration (2•644, 1•687-4•143, p<0•0001), gastrointestinal upset (1•995, 1•304-3•051, p=0•0014), and general unwellness (2•360, 1•428-3•900, p=0•0008) compared with the placebo group. Adverse event rates were similar between groups during treatment (SIM01 22 [10%] of 232 vs placebo 25 [11%] of 231; p=0•63). Treatment with SIM01, infection with omicron variants, vaccination before COVID-19, and mild acute COVID-19, were predictors of symptom alleviation (p<0•0036). Interpretation Treatment with SIM01 alleviates multiple symptoms of PACS. Our findings have implications on the management of PACS through gut microbiome modulation. Further studies are warranted to explore the beneficial effects of SIM01 in other chronic or post-infection conditions.
Contributors RIL and QS conceived the study, accessed and verified all the data, and prepared the manuscript. ISFL, MCSW, LHSL, and SWHC contributed to participant recruitment and clinical assessment. JYLC contributed to clinical data management and study monitoring. HMT and CKPM contributed to cytokines profiling. YKT provided important comments on statistical analysis. CPC contributed to sample collection and biobank management. MKTL contributed to sample processing and metagenomic sequencing. GTYY and PKC provided important assistance during the clinical trial. FKLC and SCN designed the study and contributed to data interpretation and manuscript writing. All authors read, revised, and had final responsibility for the decision to submit the manuscript for publication and had full access to all the data in the study.
Declaration of interests All authors have completed the Unified Competing Interest form (available on request to the corresponding author). MCSW is an advisory committee member of Pfizer, an external expert of GlaxoSmithKline, a member of the advisory board of AstraZeneca, and has been paid consultancy fees for providing advice on research. LHSL is supported by grants from the Health and Medical Research Fund, General Research Fund, and Direct Grant for Research; received honoraria as a speaker for Olympus, Boston Scientific, and GenieBiome; travel grants from Olympus, Pfizer, and AbbVie; and received research product support from GenieBiome for his other..
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