Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial

Abstract

Intestinal bacteria may influence lung homeostasis via the gut-lung axis. We conducted a single-center, quadruple-blinded, randomized trial in adult symptomatic Coronavirus Disease 2019 (Covid19) outpatients. Subjects were allocated 1:1 to probiotic formula (strains Lactiplantibacillus plantarum KABP022, KABP023, and KAPB033, plus strain Pediococcus acidilactici KABP021, totaling 2 × 10 9 colony-forming units (CFU)) or placebo, for 30 days. Co-primary endpoints included: i) proportion of patients in complete symptomatic and viral remission; ii) proportion progressing to moderate or severe disease with hospitalization, or death; and iii) days on Intensive Care Unit (ICU). Three hundred subjects were randomized (median age 37.0 years [range 18 to 60], 161 [53.7%] women, 126 [42.0%] having known metabolic risk factors), and 293 completed the study (97.7%). Complete remission was achieved by 78 of 147 (53.1%) in probiotic group compared to 41 of 146 (28.1%) in placebo (RR: 1.89 [95 CI 1.40–2.55]; P < .001), significant after multiplicity correction. No hospitalizations or deaths occurred during the study, precluding the assessment of remaining co-primary outcomes. Probiotic supplementation was well-tolerated and reduced nasopharyngeal viral load, lung infiltrates and duration of both digestive and non-digestive symptoms, compared to placebo. No significant compositional changes were detected in fecal microbiota between probiotic and placebo, but probiotic supplementation significantly increased specific IgM and IgG against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) compared to placebo. It is thus hypothesized this probiotic primarily acts by interacting with the host’s immune system rather than changing colonic microbiota composition. Future studies should replicate these findings and elucidate its mechanism of action (Registration: NCT04517422). Abbreviations: AE: Adverse Event; BMI: Body Mass Index; CONSORT: CONsolidated Standards of Reporting Trials; CFU: Colony-Forming Units; eDRF: Electronic Daily Report Form; GLA: Gut-Lung Axis; GSRS: Gastrointestinal Symptoms Rating Scale; hsCRP: High-sensitivity C-Reactive Protein; HR: Hazard Ratio; ICU: Intensive Care Unit; OR: Odds Ratio; PCoA: Principal Coordinate Analysis; RR: Relative Risk; RT-qPCR: Real-Time Quantitative Polymerase Chain Reaction; SARS-CoV2: Severe acute respiratory syndrome coronavirus 2; SpO 2 : Peripheral Oxygen Saturation; WHO: World Health Organization

Evaluation of a throat spray with lactobacilli in COVID-19 outpatients in a randomized, double-blind, placebo-controlled trial for symptom and viral load reduction

“…However, it should be noted that the authors did not report any correction for multiple testing in this study, which is also not yet peer reviewed. In another larger trial (n = 300) with an oral probiotic mixture of L. plantarum strains and Pediococcus acidilactici KABP021, patients in the verum group reported fewer days of fever, cough, headache, body aches and shortness of breath [8].…”

“…While oral administration of such microbiome therapeutics or probiotics remains most common [7], this route relies on systemic effects to ameliorate respiratory infections. Also during the current COVID-19 pandemic, oral administrations targeting the gut have already been explored [8][9][10]. Alternatively, topical application of rationally-selected probiotics in the airways might offer several advantages [11], as this could lead to direct blocking or inhibition of respiratory viruses [12], and direct immune modulation at the site of infection and inflammation [13,14].…”

Use of dietary supplements and OTC products in the era of COVID-19

“…18 Additionally, the probiotic supplementation was well-tolerated and reduced nasopharyngeal viral load and lung infiltrates as well as the duration of both digestive and nondigestive symptoms in comparison to the placebo. 18…”

“…Another study was conducted in 300 adult symptomatic outpatients with COVID-19. 18 Patients were randomized to a probiotic formula or placebo for 30 days, with 293 patients completing the study. 18 Complete symptomatic and viral remission was achieved by 78 of 147 patients (53.1%) in the probiotic group compared to 41 of 146 patients (28.1%) in the placebo group.…”

“…18 Patients were randomized to a probiotic formula or placebo for 30 days, with 293 patients completing the study. 18 Complete symptomatic and viral remission was achieved by 78 of 147 patients (53.1%) in the probiotic group compared to 41 of 146 patients (28.1%) in the placebo group. 18 Additionally, the probiotic supplementation was well-tolerated and reduced nasopharyngeal viral load and lung infiltrates as well as the duration of both digestive and nondigestive symptoms in comparison to the placebo.…”