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 11 to probiotic formula (strains Lactiplantibacillus plantarum KABP022, KABP023, and KAPB033, plus strain Pediococcus acidilactici KABP021, totaling 2 × 109 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; SpO2 Peripheral Oxygen Saturation; WHO World Health Organization.