In recovered COVID-19 patients, emerging global data have reported the presence of longCOVID, that is, at least one symptom that an alternative diagnosis cannot explain hasbeen persistent for four or more weeks after the initial infection. We demonstratedpreviously that almost 80% of recovered COVID-19 patients in Hong Kong suffer from LongCOVID for more than 6 months, affecting multiple body systems.In a recent study, the five most common Long COVID symptoms were fatigue, memory problem,difficulty sleeping, anxiety and hair loss. One promising hypothesis is the involvementof the gut microbiota, a collection of the trillions of gut microorganisms that playimportant immunomodulatory roles against infections.Faecal microbiota transplantation (FMT), which is the infusion of processed faeces fromhealthy donors to the gut of affected subjects, has shown impressive therapeutic effectsfor recurrent Clostridioides difficile infection and other emerging indications. Gutmicroorganisms together with the metabolites in the donated faeces could potentiallymodulate the gut microbiota of the recipient and treat the dysbiosis associated withpathological health conditions. To date, no study has yet to assess the therapeuticeffects of FMT in post-COVID-19 neuropsychiatric conditions.
Coronavirus Disease 2019 (COVID-19) is the disease caused by a novel coronavirus SARS-
CoV-2. In recovered COVID-19 patients, emerging global data have reported the presence of
Long COVID, a condition where at least one symptom that cannot be explained by
alternative diagnosis has been persistent for four or more weeks after the initial
infection. We demonstrated previously that almost 80% of recovered COVID-19 patients in
Hong Kong suffer from Long COVID for more than 6 months, affecting multiple body systems.
In a recent study, the five most common Long COVID symptoms were fatigue, memory problem,
difficulty sleeping, anxiety and hair loss. Current treatment for Long COVID only
involves symptomatic care, as the exact mechanisms underlying the pathogenesis are still
largely unknown. One promising hypothesis is the involvement of the gut microbiota, a
collection of the trillions of gut microorganisms that play important immunomodulatory
roles against infections. Our recently published findings have shown that patients with
Long COVID had a less diverse gut microbiota with significantly fewer health-associated
commensal bacteria than those without Long COVID. Previous studies have also proved the
association between the gut microbiota and insomnia, circadian disturbance and affective
disorders. Thus, gut microbiota modulation could be a novel therapeutic strategy for
these neuropsychiatric conditions.
Faecal microbiota transplantation (FMT), which is the infusion of faeces from healthy
donors to the gut of affected subjects, has shown impressive therapeutic effects for
various diseases. To date, no study has yet to assess the therapeutic effects of FMT in
post-COVID-19 neuropsychiatric conditions. In this pilot open-label study, we aim to
explore the efficacy of FMT in improving neuropsychiatric symptoms including but not
limited to insomnia severity, sleep quality, anxiety and fatigue in recovered COVID-19
patients. FMT will be administrated via Oesophago-gastro-duodenoscopy (OGD) and Flexible
Sigmoidoscopy (FS). Two arms will be recruited in a 1:1 ratio. The intervention group
will receive FMT while the control group will not receive FMT. Both groups will have the
same assessments. Subjects will receive FMT via OGD at week 0, week 2, week 4 and week 8,
and via FS at week 0. Final follow-up will be scheduled at weeks 8 and 12 for clinical
assessment. To assess the efficacy of FMT in improving neuropsychiatric symptoms,
subjects will have to fill in study questionnaires at baseline, week 8 and week 12.
Subjects will also be asked to fill in a sleep diary daily until week 12.
Procedure: Faecal Microbiota Transplantation
FMT at baseline, week 2, week 4, week 8
Both the interventional group and control group will meet the criteria below and the
control group will be age- and sex-matched subjects with the interventional group.
Inclusion Criteria:
- Individuals aged 18 and above
- Subjects who were recovered cases of COVID-19 confirmed by RT-PCR or rapid antigen
test (RAT)
- Subjects who had insomnia symptoms of post-acute COVID-19 syndrome at screening
visit
Exclusion Criteria:
- Confirmed current active malignancy
- Had abdominal surgery
- Known history of severe organ failure (including decompensated cirrhosis), renal
failure on dialysis, suffering from human immunodeficiency virus infection;
- Known pregnancy
- Mental retardation or inability to provide informed consent
- Contraindications to upper GI endoscopy
Prince of Wales Hospital
Hong Kong, Hong Kong
Siew Chien Ng, PhD, FRCP, Principal Investigator
Chinese University of Hong Kong