Discussion:
This study showed that 3 participants in placebo group got SARS-COV2
infection in comparison to no participant in synbiotic group. Although
there was a lower number of involved persons in synbiotic group, the
difference was not statistically significant. This may be partly due to
small sample size, however, as even a small reduction in COVID-19
involvement is still promising, larger studies are critically needed.
While vaccines will not be widely available in the near future for
general population in many countries, additional preventive strategies
are urgently needed especially in high risk groups including health care
providers and hospital staffs.
There are many evidences that communications exist between gut and lung,
which is called the gut-lung axis. To our knowledge, this is the first
report of synbiotic application for prevention of COVID-19 and there is
no other published trial using probiotic or prebiotic for prevention or
treatment of this novel disease. There are some animal studies and very
nice reviews that suggest specific strains of probiotics are effective
against corona viruses and presumably, SARS-COV2. Julio Villena and
Haruki Kitazawa have summarized the information regarding the effect of
L. rhamnosus CRL1505 in the beneficial modulation of the mucosal
antiviral immune response and suggest that this strain could be
beneficial in the prevention and/or the reduction of the severity of
infections caused by SARS-COV2[14]. They also concluded that
immunobiotic interventions are mostly effective in the prevention of
respiratory infections while they rarely influence the course of
infection once the pathogen has started its replication in the host and
immunobiotics should be considered as a strategy for prevention rather
than as a therapeutic option.
Some patients with COVID-19 have intestinal microbial dysbiosis with low
numbers of probiotic species such as Bifidobacterium and Lactobacillus
which could be an indicator of their weak immunity, and therefore
prebiotic, probiotic or synbiotic supplementation will help to
re-normalize the intestinal flora balance and decrease the risk of
infection[14].
Zuo and coworkers compared the fecal microbiota of fifteen patients
infected with SARS-Cov2 to healthy controls and showed thatCoprobacillus spp. Clostridium ramosum andClostridium hatherwayi were associated with severity of COVID-19
symptoms[23]. Geva-Zatorsky demonstrated that Coprobacillusspp. can upregulate ACE2 (which is a receptor for virus entry) in the
murine guts[24]. Beneficial effects include enhancement of the
intestinal epithelial barrier, competition with pathogens for nutrients
and adhesion, production of anti-microbial agents and modulation of the
host immune system[25].
A recent systematic review and meta-analysis in 2020 concluded that
synbiotic interventions reduced the incidence rate of respiratory tract
infections (RTIs) by 16% and the proportion of participants
experiencing RTIs by 16%[19]. Interestingly, Synbiotic intervention
reduced the episodes of viral respiratory infections even in asthmatic
children[14].
Our study showed that participants in synbiotic had less
gastrointestinal symptoms. This era is another potential beneficial
effect of the application of immunobiotics as diarrhea is a frequent
symptom in 10 to 30% of patients infected with SARSCoV-2. Animal
studies demonstrated that L. plantarum Probio-38 and L. salivarius
Probio-37 were capable of reducing the replication of transmissible
coronavirus. A mixture of probiotic strains was also capable of
improving the immune system of pigs infected with coronavirus and
improved their reproductive performance (Tsukahara et al., 2018).
Interestingly, it was recently reported that a multi-strain probiotic
mixture significantly reduced the fecal shedding of the feline
coronavirus in cats infected with the pathogen[14].
Mak et al. reported that 58–71% of patients with COVID-19 in China
were consumed antibiotics, and antibiotic-associated diarrhea occurred
in 2–36% of patients. Probiotics intervention has been proposed to
make these COVID-19 patients less prone to secondary infections[26].
In our study, one participant in placebo group versus no one in
synbiotic group had anosmia. Dysgeusia and anosmia are common
comorbidities in COVID-19 patients. Epidemiological studies have
demonstrated that the incidence rate of olfactory problems in COVID-19
patients varies from 33.9-68% with female dominance [27]. There are
some ongoing trials using intranasal probiotics for prevention and
treatment of COVID-19. Their results will be interesting as to whether
local use or probiotics produce inhibitory effects on olfactory problems
(ClinicalTrials.gov Identifier: NCT04458519).
In COVID-19 patients, the main manifestations are fever and cough,
lymphocytopenia and ground-glass changes on chest computed tomography
[27]. In the current trial, fever and chill were seen in two cases
in placebo group compared to one case in synbiotic group with no
statistically significant difference.
Finally, although it seems that probiotics and synbiotic should be used
mainly as a preventive strategy against COVID-19, there are some
evidences that show they may also help patients after infection with
SARS-COV2[28]. Interestingly, in an RCT of 65 critically ill,
mechanically ventilated patients, a multi-strain synbiotic containing
Pediococcus pentosaceus, Leuconostoc mesenteroides, L. paracasei ssp.
Paracasei 19, L. plantarum plus inulin, oat bran, pectin, and resistant
starch lowered the rate of infections, sepsis, days of admission in the
intensive care unit, days under mechanical ventilation, and
mortality[29].
Controversy still exists as some experts believe that blind use of
probiotics for COVID-19 is not recommended until we have a better
understanding of the pathogenesis of SARS-CoV-2 and its effect on gut
microbiota [30].
The main limitation of this study was the small sample size. Many
hospital staff were excluded from the study for their positive past
clinical history or laboratory results of COVID-19. The strengths of
this study were the novelty of application of synbiotic in COVID-19 and
the study population, health care workers, which are in high risk group
and any data regarding the prevention of COVID-19 in this population are
highly needed.