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A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial
Raphaela I Lau, Qi Su, Ivan S F Lau, et al
Lancet Infect Dis Published: December 07, 2023
DOI: https://doi.org/10.1016/S1473-3099(23)00685-0
Summary
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.
2019 新冠肺炎長期綜合後遺症 (長新冠) 影響全球超過 6500 萬⼈，但⽬前仍缺乏有效的治療⼿段。
本研究旨在評估合⽣製劑 (SIM01) 對緩解長新冠症狀的臨床效果。
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.
這項隨機、雙盲、安慰劑對照研究於香港威爾斯親王醫院進⾏。根據美國疾病管制與預防中⼼
(CDC) 標準確診的長新冠患者以 1:1 比例被隨機分成兩組，分別⼝服 SIM01 (100 億 CFU 每⽇兩次) 或
安慰劑 6 個⽉。研究納入標準為新冠確診 4 週後出現以下⾄少⼀種長期症狀，包括疲勞、記憶⼒減退、
注意⼒下降、失眠、情緒紊亂、脫髮、呼吸急促、咳嗽、無法做運動、胸痛、肌⾁痛、關節痛、腸胃不
適或整體不適。排除標準包括免疫功能低下、懷孕或哺乳、無法⼝服液體、或在研究前 30 天內有腸胃
⼿術史。受試者、醫護⼈員及研究⼈員對分組不知情。主要療效指標為 6 個⽉後長新冠症狀減輕，症狀
評估由研究⼈員就 14 種長新冠症狀作問卷調查進⾏確認。本研究採⽤治療意向分析法 (ITT) 和
Bonferroni 多重比較校正法 (p=0.0036)，並以前向逐步多變量邏輯回歸分析影響症狀緩解的因素。本研
究已在美國臨床試驗數據庫註冊，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).
在 2021 年 6 ⽉ 25 ⽇⾄ 2022 年 8 ⽉ 12 ⽇期間，463 名患者被隨機分配服⽤ SIM01 (n=232) 或安
慰劑 (n=231)。6 個⽉後，SIM01 組比安慰劑組較多受試者達到症狀緩解，包括疲勞 (OR 2.273, 95% CI
1.520–3.397, p=0.0001)、記憶⼒減退 (1.967, 1.271–3.044, p=0.0024)，注意⼒下降 (2.644, 1.687–
4.143, p<0.0001)、 腸 胃 不 適 (1.995, 1.304–3.051, p=0.0014)、 及 整 體 不 適 (2.360, 1.428–3.900,
p=0.0008)。治療期間兩組的不良事件發⽣率沒有顯著分別 (SIM01 22/232 [9%] vs 安慰劑 25/231 [11%];
p=0.63)。 SIM01 治療、Omicron 變異株感染、COVID-19 前疫苗接種史、以及 COVID-19 輕症為症狀
緩解的預測因素 (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.
合⽣製劑 SIM01 可緩解多種長新冠症狀。本研究的結果對通過調整腸道微⽣物群的長新冠治療具
有重要意義。未來的研究可探索 SIM01 在其他慢性疾病或感染後遺症的治療作⽤。
Funding
Health and Medical Research Fund of Hong Kong, Hui Hoy and Chow Sin Lan Charity Fund, and InnoHK of the HKSAR Government.
香港醫療衛⽣研究基⾦、許海周倩蘭慈善基⾦、香港特別⾏政區政府 InnoHK
Translation
For the Chinese translation of the abstract see Supplementary Materials section.
