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
  1. 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.
  2. 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.
  3. 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.