Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial
Pedro Gutiérrez-Castrellón, Tania Gandara-Martí, Ana T Abreu Y Abreu, Cesar D Nieto-Rufino, Eduardo López-Orduña, Irma Jiménez-Escobar, Carlos Jiménez-Gutiérrez, Gabriel López-Velazquez, Jordi Espadaler-Mazo
Gut Microbes, doi:10.1080/19490976.2021.2018899
Intestinal bacteria may influence lung homeostasis via the gut-lung axis. We conducted a singlecenter, 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 coprimary 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).
Author contributions PGC, JEM, and ATAA designed the study. TGM, CDNR, and IJE performed patient procedures. ELO and GLV performed laboratory analyses. CJG and PGC collected and curate the data. PGC conducted the statistical analyses. PGC and JEM drafted the manuscript. ATAA critically revised the manuscript.
Disclosure statement ATAA reports receiving speaker fees from AB-Biotics SA (Kaneka Group). JEM is a staff scientist with no stock options or shares at AB-Biotics SA (Kaneka Group). Other authors report their institution was sponsored by AB-Biotics SA (Kaneka Group) for the submitted work.
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