Long COVID: Gut microbiome modulation alleviates neuropsychiatric and GI symptoms

Modulation of gut microbiome using the SIM01 synbiotic formula significantly improves neuropsychiatric and gastrointestinal (GI) symptoms of long COVID, according to results of the randomized, triple-blind, placebo-controlled RECOVERY study conducted by researchers from the Chinese University of Hong Kong (CUHK).

The results, presented at a late-breaking abstract plenary session at the Digestive Disease Week (DDW) 2023, showed relative benefit increase (RBI) of 29.8–61.8 percent in memory and concentration problems, fatigue, general unwellness, and GI symptoms with SIM01 vs placebo. [Lau RI, et al, DDW 2023, abstract 913a]

The study, supported by the Health Bureau of Hong Kong, included 463 recovered COVID-19 patients (mean age, 49 years; female, 65.4 percent) who had ≥1 long COVID symptom (eg, fatigue, memory or concentration problems, insomnia, anxiety or sadness, hair loss, GI symptoms, shortness of breath, cough, inability to exercise, chest pain, or muscle or join pain) at ≥4 weeks after COVID-19 diagnosis.

Recruited in 2021–2022, nearly 70 percent of the participants were suspected to have been Omicron-infected. They were enrolled at a median of 4 months after COVID-19 diagnosis and randomized 1:1 to receive SIM01 (orally, 20 billion CFU/day) or a low-dose vitamin C placebo (orally, 2 mg/day) for 6 months. The primary outcome was alleviation of long COVID symptoms by month 6, assessed by an interviewer-administered 14-item symptom questionnaire. The secondary outcome was reduction of GI symptom severity, evaluated by a self-report 8-item GI symptom severity scale.

At 6 months, significantly more participants in the SIM01 vs placebo group had improvements in concentration problems (62.3 percent vs 38.5 percent; p=0.00002; RBI, 61.8 percent), memory problems (42.0 percent vs 26.9 percent; p=0.002; RBI, 56.1 percent), fatigue (62.8 percent vs 42.6 percent; p=0.00006; RBI, 47.4 percent), general unwellness (77.3 percent vs 59.0 percent; p=0.0007; RBI, 30.8 percent), and GI symptoms (70.2 percent vs 54.1 percent; p=0.001; RBI, 29.8 percent).

Adverse events (AEs) and serious AEs (SAEs) were reported in 22 vs 25 and 5 vs 1 participant(s) in the SIM01 vs placebo group, respectively. According to the investigators, all AEs and SAEs were unlikely to be associated with study products.

“Metagenomics analysis of the participants’ stool samples was also conducted. At 6 months, SIM01 recipients showed improvements in gut microbiome diversity [p=0.0019], richness [p=0.051] and composition [p=0.00041], whereas no significant changes were observed in the placebo group,” reported Professor Siew Ng, Director of the Microbiota I-Centre, CUHK. “Increased abundance of favourable bacteria, decreased abundance of unfavourable bacteria, and reduction of antibiotic resistance genes were also observed in the SIM01 group.”

“These findings suggest that restoring healthy gut microbiota may be a novel approach to improving neurological symptoms of long COVID, via beneficial metabolites and neurotransmitters produced by gut bacteria that are circulated to the brain,” suggested Ng.

“In Hong Kong, at least 2,800 patients had been diagnosed with long COVID at general outpatient clinics between August 2022 and February 2023. Findings of our study have important implications on primary healthcare and clinical management of long COVID due to the large number of patients affected and the breadth of symptoms, some of which cannot be effectively treated with existing pharmacotherapy,” said Professor Martin Wong of the Jockey Club School of Public Health and Primary Care, CUHK.

“We have submitted our findings to the Hospital Authority in the hope of benefitting the public at large,” said Professor Francis Chan, Dean of Medicine and Director of the Centre for Gut Microbiota Research, CUHK.