Method:
Participants: This study was a randomized, double blind,
placebo-controlled trial that was done during the second wave of
COVID-19 pandemic (July to August 2020) in Mashhad, the second most
popular city in Iran. Subjects were recruited from employees of
emergency department of Imam Reza and Akbar hospital, COVID 19
referral centers in Mashhad. Participants were invited through
banners. Sixty persons without any history of clinical or laboratory
evidence of SARS-Cov2 infection participated in the trial. Exclusion
criteria included: History of COVID-19 infection, Positive antibody or
RT-PCR against SARS-Cov2, history of autoimmune disorders, pregnancy,
immunosuppressive drugs use, or any chronic lung diseases. All
participants signed informed consent form.
Figure 1: Flow chart of the study
- Study design: Participants in synbiotic group received once daily oral
synbiotic capsule (Lactocare®) that contains 1 billion CFU/Cap of
Lactobacillus casei, Lactobacillus rhamnosus, Streptococcus
thermophilus, Bifidobacterium breve, Lactobacillus acidophilus,
Bifidobacterium infantis, Lactobacillus bulgaricus, and
Fructooligosacharide (Zist Takhmir, Tehran, Iran) or placebo in the
same appearance for 30 days. They were followed up at 15 and 45 days
by phone call and after first and second month visited in clinic. If
suspected symptoms and signs of COVID-19 were occurred, SARS-Cov2
RT-PCR with nasal or oral swab was done.
- Sample size and randomization: All participants (60 persons) were
active hospital staff of emergency department in Imam Reza and Akbar
hospital, working at least 40 hours per week, and who had no evidence
of novel coronavirus infection at the time of trial entrance or before
it. They were randomly divided to synbiotic and placebo groups.
According to previous studies that showed a 20-30% reduction[22]
in common colds with a probiotic, we estimated a sample size of 28 in
each group using an α value of 0.05 with a power of 90% and possible
20% follow-up loss.
- Statistical analysis: Statistical analysis was done by statistical
package for social sciences (SPSS) software version 16.0 (IBM Inc.,
Chicago, Il, USA). The IBM SPSS Statistical Software for Windows
version 22.0 (IBM Corp., Armonk, N.Y., USA) was used for the
statistical analyses. The standard descriptive statistics were applied
to describe the pattern of the data. The Chi-square and Fisher’s exact
tests were used to examine the significance of associations between
categorical data. All tests were two-tailed, and the probability value
of 0.05 was considered significant.
Ethical consideration: This trial protocol was approved by Mashhad
University of Medical Sciences ethical committee (code:
IR.MUMS.REC.1399.240). The study protocol was registered in Iranian
registry of clinical trials. (Code: IRCT20101020004976N6). The authors
have no conflict of interests. This article was funded by the Deputy of
Research at Mashhad University of Medical Sciences.