Summary of COVID-19 probiotics studies

1. Kolesnyk et al., The role of nutritional support with probiotics in outpatients with symptomatic acute respiratory tract infections: a multicenter, randomized, double-blind, placebo-controlled dietary study

73 patient probiotics early treatment RCT: 60% improved recovery (p=0.02) and 68% lower PASC (p=0.008).
RCT 73 outpatients with mild COVID-19 showing improved recovery and increased RBD/spike antibody response with 28 days of a multi-strain probiotic (Bifidobacterium (B.) lactis BI040, B. longum BL020, Lactobacillus (L) rhamnosus LR110, L. casei LC130, L. acidophilus LA120, 5 billion CFU total).
Jan 2024, BMC Nutrition, https://bmcnutr.biomedcentral.com/articles/10.1186/s40795-023-00816-8, https://c19p.org/kolesnyk

2. Di Pierro et al., The administration of S. salivarius K12 to children may reduce the rate of SARS-CoV-2 infection

128 patient probiotics prophylaxis RCT: 98% fewer cases (p<0.0001).
Interim report on an RCT for prophylactic treatment with S. salivarius K12, showing significantly lower cases with treatment. Only patients with symptoms or known positive contacts were tested. Trial identification/registration details are not provided.
Mar 2021, Minerva Medica, https://www.minervamedica.it/en/journals/minerva-medica/article.php?cod=R10Y2021N04A0514, https://c19p.org/dipierro3

3. Saviano et al., COVID-19 Pneumonia and Gut Inflammation: The Role of a Mix of Three Probiotic Strains in Reducing Inflammatory Markers and Need for Oxygen Support

80 patient probiotics late treatment RCT: 86% lower ICU admission (p=0.24) and 26% shorter hospitalization (p=0.52).
RCT 80 COVID-19 interstitial pneumonia patients in Italy, 40 treated with probiotics, showing significantly reduced gut inflammatory markers with treatment, and lower ICU admission and mortality, without statistical significance. Bifidobacterium lactis LA 304, lactobacillus salivarius LA 302, and lactobacillus acidophilus LA 201 bid for 10 days.
Jun 2022, J. Clinical Medicine, https://www.mdpi.com/2077-0383/11/13/3758, https://c19p.org/saviano

4. Haran et al., Targeting the Microbiome With KB109 in Outpatients with Mild to Moderate COVID-19 Reduced Medically Attended Acute Care Visits and Improved Symptom Duration in Patients With Comorbidities

350 patient probiotics early treatment RCT: 50% fewer combined hospitalization/ER visits (p=0.13) and 20% faster recovery (p=0.1).
RCT 350 COVID+ outpatients in the USA, 174 treated with prebiotic KB109 (a microbiome metabolic therapy candidate), showing lower combined hospitalization, ER, and urgent care visits with treatment. NCT04414124.
Mar 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.03.26.21254422, https://c19p.org/haran

5. Wischmeyer et al., Daily Lactobacillus Probiotic versus Placebo in COVID-19-Exposed Household Contacts (PROTECT-EHC): A Randomized Clinical Trial

182 patient probiotics prophylaxis RCT: 33% fewer moderate/severe cases (p=0.15), 38% fewer symptomatic cases (p=0.02), 27% faster recovery (p=0.37), and 43% fewer cases (p=0.17).
RCT 182 COVID-19 exposed patients, 91 treated with daily probiotic Lactobacillus rhamnosus GG starting a median of 3 days from exposure, showing lower symptomatic COVID-19 with treatment. There were no hospitalizations or deaths.
Jan 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.01.04.21268275, https://c19p.org/wischmeyer

6. Gutiérrez-Castrellón et al., Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial

293 patient probiotics early treatment RCT: 35% improved recovery (p<0.0001).
RCT 293 outpatients in Mexico, 147 treated with a probiotic composed of three L. plantarum strains (KABP022, KABP023 and KABP033) and one P. acidilacti strain (KABP021), showing improved recovery with treatment. There were no hospitalizations or deaths.
May 2021, Gut Microbes, https://www.tandfonline.com/doi/pdf/10.1080/19490976.2021.2018899, https://c19p.org/gutierrezcastrellon

7. Ceccarelli et al., Oral Bacteriotherapy in Patients With COVID-19: A Retrospective Cohort Study

200 patient probiotics late treatment study: 64% lower mortality (p=0.003) and 15% lower ICU admission (p=0.6).
Retrospective 200 severe condition hospitalized patients in Italy, 88 treated with probiotic Sivomixx, showing lower mortality with treatment.
Jan 2021, Frontiers in Medicine, https://internal-journal.frontiersin.org/articles/10.3389/fnut.2020.613928/full, https://c19p.org/ceccarelli

8. Di Pierro et al., Role of S. salivarius K12 in the prevention of URTI and AGE in nursery-aged children

287 patient probiotics prophylaxis study: 78% fewer cases (p=0.007).
Retrospective study of 287 nursery school children in Italy, 186 treated with S. salivarius K12 probiotic. The probiotic group had significantly lower rates of COVID-19, bronchitis, sinusitis, and laryngitis as well as lower antibiotic use. The study was registered retrospectively and details of COVID-19 diagnosis are not provided. Parents that administer the treatment may also use other treatments or take other actions that reduce risk for their children.
Sep 2023, Minerva Medica, https://www.minervamedica.it/index2.php?show=R10Y9999N00A23092804, https://c19p.org/dipierro7

9. d'Ettorre et al., Challenges in the Management of SARS-CoV2 Infection: The Role of Oral Bacteriotherapy as Complementary Therapeutic Strategy to Avoid the Progression of COVID-19

70 patient probiotics late treatment study: 87% lower mortality (p=0.14) and 88% lower progression (p=0.01).
Retrospective 70 hospitalized patients in Italy, 28 treated with probiotic Sivomixx, showing lower risk of respiratory failure and faster recovery with treatment.
Jul 2020, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2020.00389/full, https://c19p.org/dettorre

10. Trinchieri et al., Exploiting Bacteria for Improving Hypoxemia of COVID-19 Patients

35 patient probiotics late treatment study: 78% lower mortality (p=0.28) and 78% improvement (p=0.0001).
Retrospective COVID-19 patients requiring CPAP, 21 treated with SLAB51 probiotics and 15 control patients, showing improved outcomes with treatment, despite significantly lower blood oxygenation at baseline in the treatment group.
Jul 2022, Biomedicines, https://www.mdpi.com/2227-9059/10/8/1851, https://c19p.org/trinchieri

11. Catinean et al., Ongoing Treatment with a Spore-Based Probiotic Containing Five Strains of Bacillus Improves Outcomes of Mild COVID-19

120 patient probiotics prophylaxis study: 40% improved recovery (p=0.008).
Retrospective 60 patients in Romania taking probiotics and 60 matched controls, showing faster symptom resolution with the use of probiotics. Spore-based probiotic containing five strains of Bacillus.
Jan 2023, Nutrients, https://www.mdpi.com/2072-6643/15/3/488, https://c19p.org/catinean

12. Ahanchian et al., Synbiotic for Prevention of SARS-Cov2 Infection in High Risk Hospital Staffs: A Randomized Controlled Trial

60 patient probiotics prophylaxis RCT: 73% fewer symptomatic cases (p=0.35) and 85% fewer cases (p=0.24).
Small RCT 60 healthcare workers in Iran, showing lower cases with treatment but without statistical significance. Once daily oral synbiotic capsule (Lactocare®) containing 1 billion CFU L. (Lactobacillus) casei, L. rhamnosus, Streptococcus thermophilus, Bifidobacterium breve, L. acidophilus, Bifidobacterium infantis, L. bulgaricus, and Fructooligosacharide.
May 2021, Open J. Nursing, https://www.scirp.org/journal/paperinformation.aspx?paperid=108986, https://c19p.org/ahanchian

13. Zhang et al., Probiotics use is associated with improved clinical outcomes among hospitalized patients with COVID-19

300 patient probiotics late treatment study: 14% shorter hospitalization (p=0.009), 14% faster recovery (p=0.02), and 17% faster viral clearance (p=0.001).
Retrospective 375 patients in China, 179 treated with probiotics (Bifidobacterium, Lactobacillus, and Enterococcus), showing improved clinical outcomes with treatment.
Aug 2021, Therapeutic Advances in Gastroenterology , https://journals.sagepub.com/doi/full/10.1177/17562848211035670, https://c19p.org/zhang3

14. Giancola et al., Efficacy of a Multistrain Synbiotic Treatment in Acute and Post-Acute COVID-19 Patients: A Double-Blind, Placebo-Controlled Randomized Trial

50 patient probiotics late treatment RCT: 33% improved recovery (p=0.32).
RCT 52 acute COVID-19 inpatients in Italy showing a multistrain synbiotic formula prevented a decrease in gut microbiota diversity and prevented decreases in lymphocyte count and hemoglobin levels compared to placebo. The probiotic group also had enrichment of beneficial bacteria and fewer neurological/neurocognitive symptoms at 6 months, although not statistically significant. Authors suggest modulating gut microbiota in acute COVID-19 through probiotics could be a useful supportive strategy.
Jul 2024, Microorganisms, https://www.mdpi.com/2076-2607/12/7/1443, https://c19p.org/giancola

15. Sarlin et al., Streptococcus salivarius Probiotics to Prevent Acute Otitis Media in Children

827 patient probiotics prophylaxis RCT: 33% fewer cases (p=1).
RCT 827 children aged 1-6 years in daycare in Finland analyzing the effectiveness of daily Streptococcus salivarius K12 oral probiotic use for 6 months in preventing acute otitis media (AOM). The probiotic group did not have a significantly lower rate of AOM requiring antibiotics compared to placebo. A secondary outcome shows no significant difference in COVID-19, with only 2 and 3 cases in the treatment and placebo groups.
Nov 2023, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2811238, https://c19p.org/sarlin

16. Navarro-López et al., Oral intake of Kluyveromyces marxianus B0399 plus lactobacillus rhamnosus CECT 30579 to mitigate symptoms in COVID-19 patients: A randomized open label clinical trial

39 patient probiotics early treatment RCT: 33% improved recovery (p=0.08).
RCT with 24 probiotics and 15 control patients in Spain, showing lower overall symptoms and lower digestive symptoms with treatment. Kluyveromyces marxianus B0399 plus lactobacillus rhamnosus CECT 30579.
Aug 2022, Medicine in Microecology, https://www.sciencedirect.com/science/article/pii/S2590097822000118, https://c19p.org/navarrolopez

17. Zhang et al., Gut microbiota-derived synbiotic formula (SIM01) as a novel adjuvant therapy for COVID-19: An open-label pilot study

55 patient probiotics late treatment study: 67% improvement (p=0.06).
Pilot study of probiotic SIM01 with 25 consecutive COVID-19 patients in Hong Kong and 30 control patients treated by a different team during the same time period, showing improved antibody formation, reduced viral load and pro-inflammatory responses, and improvements for gut dysbiosis. SIM01 contains bifidobacteria strains, galactooligosaccharides, xylooligosaccharide, and resistant dextrin (derived from metagenomic databases of COVID-19 patients and healthy patients).
Mar 2022, J. Gastroenterology and Hepatology, https://onlinelibrary.wiley.com/doi/10.1111/jgh.15796, https://c19p.org/zhang5

18. Ceccarelli et al., Oxygen Sparing Effect of Bacteriotherapy in COVID-19

69 patient probiotics late treatment study: 82% lower ICU admission (p=0.15).
Prospective analysis of 69 severe COVID-19 patients requiring non-invasive oxygen therapy, 40 treated with probiotic formulation SLAB51, showing lower oxygen requirements and higher blood levels of pO2, O2Hb and SaO2 with treatment. Authors suggest that enzymes in SLAB51 could reduce oxygen requirements in intestinal cells, resulting in more oxygen available for other organs.
Aug 2021, Nutrients, https://www.mdpi.com/2072-6643/13/8/2898, https://c19p.org/ceccarelli2

19. Shah et al., Potential of the Combination of a Systemic Enzyme Complex and Probiotics administration to Combat COVID-19: A Randomized Open Label Prospective Analysis

60 patient probiotics late treatment RCT: 11% faster recovery (p=0.19) and 11% shorter hospitalization (p=0.18).
Small RCT 60 patients in India, 30 treated with ImmunoSEB and ProbioSEB CSC3, showing faster recovery with treatment. CTRI/2020/09/027685, CTRI/2020/08/027168.
Feb 2021, Advances in Clinical Toxicology, https://advancedenzymesdirect.com/wp-content/uploads/2021/05/Covid-Published-paper.pdf, https://c19p.org/shah

20. Hassan et al., The effects of probiotic Lactobacillus acidophilus and colchicine on the control of symptoms, duration, and disease progression of mild and moderate cases of COVID-19: A randomized controlled clinical trial

100 patient probiotics early treatment RCT: 80% lower hospitalization (p=0.2) and 18% improved recovery (p=0.42).
RCT 150 patients in Egypt showing no significant difference in outcomes with probiotic lactobacillus acidophilus, although hospitalization was 2% versus 10% for control. SOC included vitamin C, D, and zinc.
Jun 2023, Research Square, https://www.researchsquare.com/article/rs-3049708/v1, https://c19p.org/hassan

21. Di Pierro et al., Clinical Effects of Streptococcus salivarius K12 in Hospitalized COVID-19 Patients: Results of a Preliminary Study

50 patient probiotics late treatment RCT: 62% lower mortality (p=0.17) and no change in ICU admission (p=1).
RCT 50 hospitalized patients in Pakistan, 25 treated with S. salivarius K12, showing lower mortality with treatment, without statistical significance. There were more patients with higher oxygen requirements at baseline in the control group - 18 vs. 6 with O2 ≥ 8 L/min.
Sep 2022, Microorganisms, https://www.mdpi.com/2076-2607/10/10/1926, https://c19p.org/dipierro6

22. Rodriguez-Blanque et al., Evaluation of the effect of Loigolactobacillus coryniformis K8 CECT 5711 consumption in health care workers exposed to COVID-19

255 patient probiotics prophylaxis RCT: 9% fewer cases (p=0.92).
Prophylaxis RCT with 127 probiotics and 128 control healthcare workers in Spain, showing no significant difference in cases. There were only 4 cases. Severity information by arm is not provided. L. coryniformis K8 CECT 5711. Treatment may help sustain the immune response to vaccination - in the subgroup of subjects for whom more than 81 days had passed since they received the first dose, IgG levels were significantly higher in the treatment group. Patients that started probiotic consumption before the first vaccine dose also reported significantly fewer side effects.
Aug 2022, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2022.962566/full, https://c19p.org/rodriguezblanque

23. Louca et al., Modest effects of dietary supplements during the COVID-19 pandemic: insights from 445 850 users of the COVID-19 Symptom Study app

372,720 patient probiotics prophylaxis study: 8% fewer cases (p=0.03).
Survey analysis of dietary supplements showing probiotic usage associated with lower incidence of COVID-19. These results are for PCR+ cases only, they do not reflect potential benefits for reducing the severity of cases. A number of biases could affect the results, for example users of the app may not be representative of the general population, and people experiencing symptoms may be more likely to install and use the app.
Nov 2020, BMJ Nutrition, Prevention & Health, https://nutrition.bmj.com/content/4/1/149, https://c19p.org/loucak

24. Holt et al., Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK)

15,227 patient probiotics prophylaxis study: 30% fewer cases (p=0.11).
Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistical significance was not reached for any of these. Except for vitamin D, the results for treatments we follow were only adjusted for age, sex, duration of participation, and test frequency. NCT04330599. COVIDENCE UK.
Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtk

25. Ivashkin et al., Efficacy of a Probiotic Consisting of Lacticaseibacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911, and Bifidobacterium longum subsp. longum PDV 2301 in the Treatment of Hospitalized Patients with COVID-19: a Randomized Controlled Trial

200 patient probiotics late treatment RCT: 2% higher mortality (p=1), 18% lower ventilation (p=1), 27% lower ICU admission (p=0.77), and 5% faster recovery (p=0.47).
RCT 200 patients, 99 treated with a probiotic (Lacticaseibacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911, and Bifidobacterium longum subsp. longum PDV 2301). There was no significant difference in mortality or recovery time, however benefits were seen for diarrhea. NCT04854941.
Oct 2021, Probiotics Antimicrob Proteins, https://pubmed.ncbi.nlm.nih.gov/34643888/, https://c19p.org/ivashkin

26. Veterini et al., Probiotics Intake as Adjunct Therapy for Infected Health-Care with SARS COV-2

30 patient probiotics early treatment study: 29% faster viral clearance (p=0.22).
Small case control analysis with 15 probiotics patients and 15 contol patients, showing no significant differences. PCR tests were only done weekly. Dosage is unknown. 115/LOE/301.4.2/IX/2020.
Jun 2021, Indian J. Forensic Medicine & Toxicology, http://medicopublication.com/index.php/ijfmt/article/view/15003/13584, https://c19p.org/veterini

27. Li et al., The role of probiotics in coronavirus disease-19 infection in Wuhan: A retrospective study of 311 severe patients

311 patient probiotics late treatment study: 12% lower hospital discharge (p=0.68) and 35% slower viral clearance (p=0.001).
Retrospective 311 severe condition hospitalized patients in China, 123 treated with probiotics, showing slower viral clearance and recovery with treatment. Authors note that probiotics were able to moderate immunity and decrease the incidence of secondary infections.
Mar 2021, Int. Immunopharmacology, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934664/, https://c19p.org/li10

28. Fernández-Ferreiro et al., Effects of Loigolactobacillus coryniformis K8 CECT 5711 on the Immune Response of Elderly Subjects to COVID-19 Vaccination: A Randomized Controlled Trial

198 patient probiotics prophylaxis RCT: 2% higher mortality (p=1), 38% slower recovery (p=0.56), 28% higher severe cases (p=0.75), and 2% more symptomatic cases (p=1).
RCT 200 nursing home residents over 60 years old in Spain showing Loigolactobacillus coryniformis K8 probiotic administration enhanced IgG antibody response in subjects previously infected with SARS-CoV-2 and tended to improve IgA antibody response in those over 85 years old not previously infected, in the context of COVID-19 vaccination. There was no significant difference in incidence of COVID-19 infection between the probiotic and placebo groups during the study. The probiotic group had a higher percentage of asymptomatic COVID-19 cases compared to placebo, without statistical significance.
Jan 2022, Nutrients, https://www.mdpi.com/2072-6643/14/1/228, https://c19p.org/fernandezferreiro

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