Irregularities in the Long COVID paper on the SIM01 synbiotic

Lau and colleagues published an interesting paper showing that their synbiotic SIM01 improved outcomes in PACS patients.

But here are the main irregularities with the Lancet Infect Dis paper:

  • The primary endpoint/outcome was changed on or before Feb 7 2023, roughly a year after patients were assigned between June 25 2021 and August 12 2022.
  • On July 19, 2023 the pre-registration was changed to state that enrollment was estimated to be 448- below the 463 number in the Lancet paper. The change to the pre-registration is strange as participants were already assigned between June 25 2021 and August 12 2022. Note: the “Statistical analysis” section of the paper provides the 448 number (“224 patients per group”).
  • The July 2023 pre-registration changed the duration of treatment from 3 months to 6 months. But by then, the treatment would have already been completed.

Other irregularities

Endpoints are vague, do not specify what the endpoint is exactly

The pre-registration’s endpoints are vague and do not specify a particular way of measuring an outcome. “Alleviation of symptoms or complications” in the pre-registration seems to refer to the PACSQ-14 questionnaire described in the supplementary material.

One of the joint first authors does not appear in the protocol

Qi Su is listed in the published paper as a joint first author.

RIL and QS conceived the study, accessed and verified all the data, and
prepared the manuscript.

However, the supplementary material lists Sien C. Ng as the principal investigator. Qi Su’s name does not appear in the supplementary material / RECOVERY_Protocol_20230421 v.7.

Testing panel used

The cytokine panel was changed from MILLIPLEX MAP (presumably by Merck Millipore) to LEGENDplex (by BioLegend). However, the supplementary materials mention both tests… which is presumably an error.

“Active” placebo

The “active placebo” from the pre-registration is described in the Lancet paper as: “Placebo consisted of a very low dose vitamin C (1 mg in sachets twice daily) and an inert substance made of starch filler, flavour, and colouring.”

  • Commercially-available Vitamin C supplements might have 500/1000mg versus the 1mg described in the Lancet paper.

The “active vitamin” described in the pre-registration does not state vitamin C like the Lancet paper does.


The pre-registration made multiple changes to the treatment:

  • 3 months → 6 months (presumably this is to correct an error or mixup with the IMPACT study)
  • 10 → 20 billion CFU (presumably it’s 2 sachets of 10B CFU daily).

The trial went from multi-center to single-center.

“Long COVID”

The inclusion criteria for the study (according to the pre-registration and protocol in the supplementary material) does not actually require the patient to have Long COVID, PACS, etc.

The original title of the study is:

A Randomised-controlled Trial of an Oral Microbiome Immunity Formula in Reducing Development of Long-term Co-morbidities in Recovered COVID-19 Patients

The title specifies recovered COVID19 patients rather than Long COVID or PACS patients.

The published paper states that US CDC criteria were used:

Inclusion criterion was the presence of at least one of 14 PACS symptoms for 4 weeks or more after confirmed SARS-CoV-2 infection

Reference 2 in the paper points to a CDC webpage. However, from April 9 to June 30 2021, that webpage only listed 12 symptoms- not 14. Thus is unlikely that they used CDC criteria when the study started on June 25 2021.

Also during June 25 2021, Long COVID was not really a hot research topic. e.g. The highly influential paper by the PLRC group was published on July 2021.

On the other hand, the recruitment page lists the following 2 criteria (according to Google Translate):

  • (1) Rapid test/nucleic acid test has been positive
  • (2) Still has one or more COVID-19 sequelae five weeks after recovery

The recruitment page is not the same as the published paper, which states:

Inclusion criterion was the presence of at least one of 14 PACS symptoms for 4 weeks or more after confirmed SARS-CoV-2 infection

5 weeks after recovery is not the same as 4 (or more) weeks after infection.

A previous paper by Lau found a PACS prevalence of 78.7%, which suggests that studied a different kind of “Long COVID” than what the support groups experience.

The bottom line

The irregularities look weird to me. Really weird. Does anybody know what’s going on?

Secondary endpoint - qualify of life scale

quality of life and physical activity were assessed by the trained interviewers using a visual analogue scale, with scores ranging from 0–100


Visual analogue scale scores on quality of life at 6 months had a mean of 76·0 (SD 12·0) for the SIM01 group and 74·5 (12·3) for the placebo group (p=0·17).

There was not a statistically significant difference in QoL.

Here’s a list of SIM01 studies:

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

Effects of Gut Microbiome Modulation on Reducing Adverse Health Outcomes among Elderly and Diabetes Patients during the COVID-19 Pandemic: A Randomised, Double-Blind, Placebo-Controlled Trial (IMPACT Study).

Those first two are used by GenieBiome / G-NiiB to advertise its SIM01 product.


Gut microbiota‐derived synbiotic formula (SIM01) as a novel adjuvant therapy for COVID‐19: An open‐label pilot study

A Probiotic Formula for Modulation of Colorectal Cancer Risk via Reducing CRC-Associated Bacteria

Commercial ties

The CUHK website promotes the work on SIM01, which was “developed by CUHK”.

This paper states:

Prof. Siew Ng and Prof. Francis Chan report serving as founder member for GenieBiome Limited

The G-NiiB website has information on where to buy SIM01. The advisors webpage lists Martin Wong of the CUHK, who appears in the CUHK website promoting SIM01. Martin Wong is the lead author of the IMPACT study.