Synbiotic Therapy of Gastrointestinal Symptoms During Covid-19 Infection

The outbreak of the novel coronavirus (SARS-CoV-2)-infected disease (COVID-19) began in
Wuhan, Hubei province in December 2019, spread throughout China in early 2020 and
developed as a pandemic thereafter. Although the virus mainly causes respiratory
symptoms, GI (gastrointestinal) presentations have been reported in and outside of China.
Patients may present with anorexia, nausea, vomiting, diarrhea and abdominal discomfort.
Also, faecal-oral transmission of the virus is currently discussed. Preliminary,
unpublished data from China suggest that patients with GI symptoms may suffer more
frequently from severe courses of the disease. Clinical studies show an incidence rate of
diarrhea ranging from 2% to 50% of cases. It may precede or trail respiratory symptoms. A
pooled analysis revealed an overall percentage of diarrhea onset of 10.4%. SARS-CoV-2
uses the angiotensin-converting enzyme 2 (ACE2) for cellular entry. ACE2 is expressed in
the small intestinal epithelia as well as in the upper esophagus, liver, and colon.
SARS-CoV-2 binding affinity to ACE2 is significantly higher (10-20 times) compared with
SARS-CoV. Diarrhea is associated with prolonged symptoms and viral carriage.

Clinical information on the characteristics of Covid-19 diarrhea is scarce. The duration
of diarrhea is around 4 days with 3-4 loose stools per day. Faecal calprotectin is
elevated in stool of patients with Covid-19 diarrhea, indicating a relation between
gastrointestinal symptoms and this well-established inflammation biomarker.

So far, no therapy is available for Covid-19 infection in general or for Covid-19 induced
diarrhea. Rehydration and potassium monitoring should be performed as in all patients
with diarrhea. It is important to underline that antivirals and antibiotics are often
used for COVID-19 treatment or treatment of bacterial superinfections, involving a likely
alteration of the gut microbiota and causing diarrhea. It is therefore plausible that the
gut microbiota could be a new therapeutic target and that probiotics or synbiotics
(combination of probiotics with prebiotics) could have a role in the management of these
patients. The China's National Health Commission recommended the use of probiotics for
the treatment of patients with severe COVID-19 in order to preserve intestinal balance
and to prevent secondary bacterial infections without any available clinical studies to
support this and probiotics apparently were used in Zhejiang during the Covid-19
pandemic. Although there is no specific data on the effects of probiotics on SARS-CoV2
infections, meta-analyses show that probiotics are effective in the treatment of upper
respiratory tract infections and viral gastroenteritis of other origins. Furthermore,
Enterococcus faecium has been shown to have antiviral effects in enteropathogenic
coronavirus transmissible gastroenteritis virus infections in piglets. We therefore aim
to assess the role of synbiotics in the therapy of Covid-19 infection with
gastrointestinal symptoms.