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

Autor:	Lau RI; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China; Microbiota I-Center, Hong Kong Special Administrative Region, China., Su Q; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China; Microbiota I-Center, Hong Kong Special Administrative Region, China., Lau ISF; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China., Ching JYL; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China; Microbiota I-Center, Hong Kong Special Administrative Region, China., Wong MCS; The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China., Lau LHS; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China., Tun HM; Microbiota I-Center, Hong Kong Special Administrative Region, China; The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China; Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China., Mok CKP; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China; Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China., Chau SWH; Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China., Tse YK; Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China; Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China., Cheung CP; Microbiota I-Center, Hong Kong Special Administrative Region, China., Li MKT; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China; Microbiota I-Center, Hong Kong Special Administrative Region, China., Yeung GTY; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China., Cheong PK; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China., Chan FKL; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China; Microbiota I-Center, Hong Kong Special Administrative Region, China; Centre for Gut Microbiota Research, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China., Ng SC; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China; Microbiota I-Center, Hong Kong Special Administrative Region, China; Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China. Electronic address: siewchienng@cuhk.edu.hk.
Jazyk:	angličtina
Zdroj:	The Lancet. Infectious diseases [Lancet Infect Dis] 2024 Mar; Vol. 24 (3), pp. 256-265. Date of Electronic Publication: 2023 Dec 07.
DOI:	10.1016/S1473-3099(23)00685-0
Abstrakt:	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. Funding: Health and Medical Research Fund of Hong Kong, Hui Hoy and Chow Sin Lan Charity Fund, and InnoHK of the HKSAR Government. Translation: For the Chinese translation of the abstract see Supplementary Materials section. Competing Interests: 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 research. FKLC is Board Member of the Chinese University of Hong Kong (CUHK) Medical Centre; is a co-founder, non-executive Board Chairman, non-executive scientific adviser, and shareholder of GenieBiome; receives patent royalties from GenieBiome through his affiliated institution, CUHK; has received fees as an adviser and honoraria as a speaker for Eisai, AstraZeneca, Pfizer, Takeda Pharmaceutica, and Takeda (China) Holdings; and received consulting fees from the American Gastroenterological Association Institute. SCN has served as an advisory board member for Pfizer, Ferring, Janssen, and AbbVie and received honoraria as a speaker for Ferring, Tillotts, Menarini, Janssen, AbbVie, and Takeda; received research grants from Olympus, Ferring, and AbbVie through her affiliated institution, CUHK; is a scientific co-founder and shareholder of GenieBiome; and receives patent royalties from GenieBiome, through CUHK. QS, HMT, FKLC, and SCN are named inventors of patent applications held by the CUHK and Microbiota I-Center that cover the therapeutic and diagnostic use of microbiome. FKLC and SCN are named inventors of a patent application related to SIM01 for improving immunity held by the CUHK, which is licensed exclusively to GenieBiome. No patents have been filed or are intended to be filed for the findings presented in this manuscript. All other authors declare no competing interests. (Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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