Randomised, double-blind, placebo-controlled trial of Probiotics To Eliminate COVID-19 Transmission in Exposed Household Contacts (PROTECT-EHC): a clinical trial protocol

Abstract

IntroductionThe COVID-19 pandemic has proven to be an unprecedented challenge to worldwide health, and strategies to mitigate the spread and severity of COVID-19 infection are urgently needed. Emerging evidence suggests that the composition of the gut microbiome and modification of microbial ecology via probiotics can affect susceptibility to a wide range of infections, including respiratory tract infections. In this study, we aim to evaluate the effects of the probiotic Lactobacillus rhamnosus GG (LGG) versus placebo on COVID-19 infection status and the gut microbiome in subjects with a household contact who has tested positive for COVID-19.Methods and analysisIn this double-blinded, randomised, placebo-controlled trial, we will randomise 1132 subjects having a household contact who has recently (≤7 days) tested positive for COVID-19 to daily oral LGG or placebo for 28 days. We hypothesise that taking LGG as a probiotic will protect against COVID-19 infection and reduce the severity of disease in those who become infected (primary endpoint: decreased symptoms), and will be associated with beneficial changes in the composition of the gut microbiome. Stool samples and nasal swabs will be collected to evaluate the microbiome by 16S rRNA sequencing and the presence of SARS-CoV-2 by PCR, respectively. We will also conduct multivariate analysis of demographic, behavioural, temporal, and other variables that may predict development of symptoms and other outcomes.Ethics and disseminationThis trial is conducted under a Food and Drug Administration Investigational New Drug for LGG, has received ethics approval by the institutional review board of Duke University and enrolment has begun. We plan to disseminate the results in peer-reviewed journals and at national and international conferences.Trial registration numberNCT04399252.

Evidences and perspectives of the use of probiotics, prebiotics, synbiotics, and postbiotics as adjuvants for prevention and treatment of COVID-19: A bibliometric analysis and systematic review

“…Arguably the COVID-19 pandemic has changed the way people live. After almost two years of pandemic, we are still learning how to prevent and treat it, and strategies to mitigate the spread of the virus and severity of the infection are extremely necessary ( Tang et al, 2021 ). In this way, it is known that the intestine and the lung, are organs that shares a relationship by influencing immune responses and inflammatory processes through the gut-lung axis, and both may respond to the treatment with pre and/or probiotics ( Baindara et al, 2021 ).…”

“… Reference Country Study type Subjects Probiotic strain Intervention Main results d’Ettorre et al (2020) Italy Single group Seventy patients with COVID-19 hospitalized Streptococcus thermophilus DSM 32345, Lactobacillus acidophilus DSM 32241 , Lactobacillus helveticus DSM 32242, Lacticaseibacillus paracasei DSM 32243, Lactiplantibacillus plantarum DSM 32244 , Levilactobacillus brevis DSM 27961 , Bifidobacterium lactis DSM 32246 , Bifidobacterium lactis DSM 32247. Daily oral 2.4 billion CFU bacteria for a period of 14 days A probiotic intervention demonstrated a significant improving on the clinical conditions of patients with COVID-19 Tang et al (2021) United States Double-blinded, randomized, placebo-controlled trial One thousand one hundred and thirty-two individuals with household contact who tested positive for COVID-19 Lacticaseibacillus rhamnosus GG (ATCC 53103) Daily oral Lacticaseibacillus rhamnosus GG or placebo for a period of 28 days Probiotics are low-cost and safe. It can serve as a rapid intervention strategy in the prevention or reduction of symptoms against pandemic diseases Endam et al (2020) Canada, Saudi Arabia, and United States Prospective randomized clinical trial Twenty-three individuals between aged 18–59 years having received lately PCR tested positive for SARS-CoV-2 Lactococcus lactis W136 Nasal irrigations through buffered isotonic solution containing 2.4 × 10 9 CFU of Lactococcus lactis W136 or buffered isotonic saline isolated for along the 2 weeks (twice daily) Probiotic intranasal intervention was correlated with a reduced number of patients showing moderate/severe symptoms of fatigue, loss of perception of smell, and sensation of breathlessness, and by an improved proportion of individuals with moderate/severe facial pain or sore throat Gutiérrez-Castrellón et al (2021) México and Spain Single-center, quadruple-blinded randomized clinical trial Three hundred outpatients with symptomatic COVID-19 (aged between 18 to 60 years) with positive nucleic acids test for SARS-CoV-2 …”

“… Tang et al (2021) performed trial a first double-blind, randomized, placebo-controlled trial of 1132 individuals who ingested L. rhamnosus GG for 28 days that had household contact with individuals who have recently (≤7 days) tested positive for COVID-19. Unfortunately, the researchers reported that the results of the of the primary and secondary outcomes have yet to be published, but this study has already revealed that probiotics are inexpensive and safe ( Tang et al, 2021 ).…”

COVID-19 associated mucormycosis: evolving technologies for early and rapid diagnosis

“…However, there are several reports and experimental studies highlighting the importance of use of probiotics as an adjunctive or prophylactic treatment for COVID-19 (He et al 2020 ; Morais et al 2020 ; Olaimat et al 2020 ; Gohil et al 2021 ; Chhibber-Goel et al 2021 ). To date, four clinical studies have used probiotics in management of COVID-19 and around six studies are being assessed for the clinical trials (Baindara et al 2021 ; Tang et al 2021 ; Peng et al 2021 ) Therefore, on the basis of the existing fundamental studies, future research could be directed toward assessing the efficacy of probiotics singly or as an adjunct with the existing management strategies in treatment of CAM. Thus, probiotics could be used to tackle the triple threat of COVID-19 i.e., as a replenisher of gut dysbiosis, as an anti-inflammatory agent, and as an antimicrobial (antifungal) agent.…”

Is the Gut Microbiome a Target for Adjuvant Treatment of COVID-19?

“…The intervention will be made by providing a probiotic consisting of Lactobacillus rhamnosus GG. In total, 182 participants are expected to enrol [86,87]. A clinical trial in Austria aims to use Omni-Biotic ® 10 AAD (Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Enterococcus faecium W54, Lactobacillus acidophilus W37, Lactobacillus acidophilus W55, Lactobacillus paracasei W20, Lactobacillus plantarum W1, Lactobacillus plantarum W62, Lactobacillus rhamnosus W71, and Lactobacillus salivarius W24) as an invention for COVID-19-related diarrhoea [88].…”