Efficacy and safety of novel probiotic formulation in adult Covid19 outpatients: a randomized, placebo-controlled clinical trial

ABSTRACT Background Probiotics have been proposed as adjuvants for Coronavirus Disease 2019 (Covid19) but randomized controlled trials (RCT) are lacking. Methods Single-center, quadruple-blinded RCT. Symptomatic Covid 19 outpatients (aged 18 to 60 years) with positive SARS-CoV2 nucleic acids test were randomized to active (n=150; ≥2×10 9 colony-forming units (CFU) of probiotic strains Lactiplantibacillus plantarum KABP022, KABP023 and KAPB033, plus strain Pediococcus acidilactici KABP021) or placebo (n=150), take orally once daily for 30 days. Oral acetaminophen was allowed and controlled as co-intervention. Primary endpoint included: i) proportion of patients in complete remission (both symptoms and nucleic acids test) or progressing to moderate or severe disease with hospitalization; ii) death rate and duration on Intensive Care Unit (ICU). Safety was assessed in all patients. This study is registered at ClinicalTrials.gov ( NCT04517422 ). Findings 300 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%). Remission was achieved by 78 of 147 (53.1%) in the active group compared to 41 of 146 (28.1%) in placebo (P<0.0001; ARR=25.0% [95%CI 14.1-35.9%]), still significant after multiplicity correction for the primary endpoint. No hospitalizations or deaths occurred during the study, precluding the assessment of efficacy on these endpoints. No serious adverse events occurred during the study. Replication studies with this probiotic formula are warranted.