Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial
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 KAB...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Gut Microbes |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/19490976.2021.2018899 |
| _version_ | 1818950293640970240 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Pedro Gutiérrez-Castrellón |
| collection | DOAJ |
| description | 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 × 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 |
| first_indexed | 2024-12-20T09:16:17Z |
| format | Article |
| id | doaj.art-27663052b13042fdb07bc2cb7daf9b9b |
| institution | Directory Open Access Journal |
| issn | 1949-0976 1949-0984 |
| language | English |
| last_indexed | 2024-12-20T09:16:17Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj.art-27663052b13042fdb07bc2cb7daf9b9b2022-12-21T19:45:24ZengTaylor & Francis GroupGut Microbes1949-09761949-09842022-12-0114110.1080/19490976.2021.20188992018899Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trialPedro Gutiérrez-Castrellón0Tania Gandara-Martí1Ana T. Abreu Y Abreu2Cesar D. Nieto-Rufino3Eduardo López-Orduña4Irma Jiménez-Escobar5Carlos Jiménez-Gutiérrez6Gabriel López-Velazquez7Jordi Espadaler-Mazo8Hospital General Dr. Manuel Gea GonzalezHospital General Dr. Manuel Gea GonzalezHospital Angeles PedregalHospital General Dr. Manuel Gea GonzalezDiagnoMol SA de CVHospital General Dr. Manuel Gea GonzalezHospital General Dr. Manuel Gea GonzalezInternational Scientific Council for ProbioticsAB-Biotics SA (KANEKA Group)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 × 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 Organizationhttp://dx.doi.org/10.1080/19490976.2021.2018899covid19sars-cov2probioticviral loadchest x-rayacquired immunitygut-lung axis |
| spellingShingle | 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 Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial Gut Microbes covid19 sars-cov2 probiotic viral load chest x-ray acquired immunity gut-lung axis |
| title | Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial |
| title_full | Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial |
| title_fullStr | Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial |
| title_full_unstemmed | Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial |
| title_short | Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial |
| title_sort | probiotic improves symptomatic and viral clearance in covid19 outpatients a randomized quadruple blinded placebo controlled trial |
| topic | covid19 sars-cov2 probiotic viral load chest x-ray acquired immunity gut-lung axis |
| url | http://dx.doi.org/10.1080/19490976.2021.2018899 |
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