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 Preliminary, unpublished data from China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.