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0 0.5 1 1.5 2+ Mortality -2% Improvement Relative Risk Ventilation 18% ICU admission 27% Recovery time 5% Probiotics  Ivashkin et al.  LATE TREATMENT  RCT Is late treatment with probiotics beneficial for COVID-19? RCT 200 patients in Russia (December 2020 - March 2021) Trial underpowered for serious outcomes c19early.org Ivashkin et al., Probiotics Antimicrob.., Oct 2021 Favors probiotics Favors control

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

Ivashkin et al., Probiotics Antimicrob Proteins, doi:10.1007/s12602-021-09858-5, NCT04854941
Oct 2021  
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Probiotics for COVID-19
17th treatment shown to reduce risk in March 2021
 
*, now known with p = 0.0000013 from 26 studies.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,100+ studies for 60+ treatments. c19early.org
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 (history).
The immune effects of probiotics are strain-specific.
risk of death, 2.0% higher, RR 1.02, p = 1.00, treatment 4 of 99 (4.0%), control 4 of 101 (4.0%).
risk of mechanical ventilation, 18.4% lower, RR 0.82, p = 1.00, treatment 4 of 99 (4.0%), control 5 of 101 (5.0%), NNT 110.
risk of ICU admission, 27.1% lower, RR 0.73, p = 0.77, treatment 5 of 99 (5.1%), control 7 of 101 (6.9%), NNT 53.
recovery time, 4.8% lower, relative time 0.95, p = 0.47, treatment 99, control 101.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Ivashkin et al., 13 Oct 2021, Randomized Controlled Trial, Russia, peer-reviewed, 11 authors, study period December 2020 - March 2021, average treatment delay 8.0 days, trial NCT04854941 (history).
This PaperProbioticsAll
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
Vladimir Ivashkin, Victor Fomin, Sergey Moiseev, Michail Brovko, Roman Maslennikov, Anatoly Ulyanin, Victoria Sholomova, Maria Vasilyeva, Elizaveta Trush, Oleg Shifrin, Elena Poluektova
Probiotics and Antimicrobial Proteins, doi:10.1007/s12602-021-09858-5
The treatment of coronavirus disease (COVID-19) and COVID-19-associated diarrhea remains challenging. This study aimed to evaluate the efficacy of a multi-strain probiotic in the treatment of COVID-19. This was a randomized, controlled, singlecenter, open-label trial (NCT04854941). Inpatients with confirmed COVID-19 and pneumonia were randomly assigned to a group that received a multi-strain probiotic (PRO group) or to the control group (CON group). There were 99 and 101 patients in the PRO and CON groups, respectively. No significant differences in mortality, total duration of disease and hospital stay, incidence of intensive care unit admission, need for mechanical ventilation or oxygen support, liver injury development, and changes in inflammatory biomarker levels were observed between the PRO and CON groups among all included patients as well as among subgroups delineated based on age younger or older than 65 years, and subgroups with chronic cardiovascular diseases and diabetes. Diarrhea on admission was observed in 11.5% of patients; it resolved earlier in the PRO group than in the CON group (2 [1-4] vs. 4 [3-6] days; p = 0.049). Hospital-acquired diarrhea developed less frequently in the PRO group than in the CON group among patients who received a single antibiotic (0% vs. 12.5%; p = 0.023) unlike among those who received > 1 antibiotic (10.5% vs. 13.3%; p = 0.696). The studied probiotic had no significant effect on mortality and changes in most biomarkers in COVID-19. However, it was effective in treating diarrhea associated with COVID-19 and in preventing hospital-acquired diarrhea in patients who received a single antibiotic.
Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1007/ s12602-021-09858-5. Author Contribution The idea and design of the study were developed by Vladimir Ivashkin and Elena Poluektova. Material preparation, data collection, and analysis were performed by all authors. The first draft of the manuscript was written by Roman Maslennikov, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Declarations Ethics Approval The study was approved by the local ethics committee (Conclusion №. 34-20 of September 9, 2020) in accordance with the Declaration of Helsinki. Consent to Participate Informed consent was obtained from all individual participants included in the study. Consent for Publication Patients' personal data are not published. Conflicts of Interest The authors declare no competing interests.
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Probiotics Antimicrob ' 'Proteins 13:611–623. https://doi.org/10.1007/s12602-020-09727-7', 'volume': '13', 'year': '2021'}, { 'DOI': '10.1038/s41538-020-00078-9', 'author': 'AN Olaimat', 'doi-asserted-by': 'publisher', 'first-page': '17', 'journal-title': 'NPJ Sci Food', 'key': '9858_CR19', 'unstructured': 'Olaimat AN, Aolymat I, Al-Holy M et al (2020) The potential application ' 'of probiotics and prebiotics for the prevention and treatment of ' 'COVID-19. NPJ Sci Food 4:17. https://doi.org/10.1038/s41538-020-00078-9', 'volume': '4', 'year': '2020'}, { 'DOI': '10.1016/j.micpath.2020.104452', 'author': 'M Mahooti', 'doi-asserted-by': 'publisher', 'journal-title': 'Microb Pathog', 'key': '9858_CR20', 'unstructured': 'Mahooti M, Miri SM, Abdolalipour E, Ghaemi A (2020) The immunomodulatory ' 'effects of probiotics on respiratory viral infections: a hint for ' 'COVID-19 treatment? Microb Pathog 148:104452. ' 'https://doi.org/10.1016/j.micpath.2020.104452', 'volume': '148', 'year': '2020'}, { 'DOI': '10.1177/2058738420961304', 'author': 'HS Bozkurt', 'doi-asserted-by': 'publisher', 'first-page': '205873842096130', 'journal-title': 'Int J Immunopathol Pharmacol', 'key': '9858_CR21', 'unstructured': 'Bozkurt HS, Quigley EM (2020) The probiotic Bifidobacterium in the ' 'management of Coronavirus: a theoretical basis. Int J Immunopathol ' 'Pharmacol 34:2058738420961304. https://doi.org/10.1177/2058738420961304', 'volume': '34', 'year': '2020'}, { 'DOI': '10.1016/j.intimp.2021', 'author': 'Q Li', 'doi-asserted-by': 'publisher', 'journal-title': 'Int Immunopharmacol', 'key': '9858_CR22', 'unstructured': 'Li Q, Cheng F, Xu Q et al (2021) The role of probiotics in coronavirus ' 'disease-19 infection in Wuhan: a retrospective study of 311 severe ' 'patients. Int Immunopharmacol 95:107531. ' 'https://doi.org/10.1016/j.intimp.2021', 'volume': '95', 'year': '2021'}, { 'DOI': '10.3389/fnut.2020.613928', 'author': 'G Ceccarelli', 'doi-asserted-by': 'publisher', 'journal-title': 'Front Nutr', 'key': '9858_CR23', 'unstructured': 'Ceccarelli G, Borrazzo C, Pinacchio C et al (2021) Oral bacteriotherapy ' 'in patients with COVID-19: a retrospective cohort study. Front Nutr ' '7:613928. https://doi.org/10.3389/fnut.2020.613928', 'volume': '7', 'year': '2021'}, { 'DOI': '10.3389/fmed.2020.00389', 'author': 'G d’Ettorre', 'doi-asserted-by': 'publisher', 'first-page': '389', 'journal-title': 'Front Med (Lausanne)', 'key': '9858_CR24', 'unstructured': 'd’Ettorre G, Ceccarelli G, Marazzato M et al (2020) Challenges in the ' 'management of SARS-CoV2 infection: the role of oral bacteriotherapy as ' 'complementary therapeutic strategy to avoid the progression of COVID-19. ' 'Front Med (Lausanne) 7:389. https://doi.org/10.3389/fmed.2020.00389', 'volume': '7', 'year': '2020'}, { 'DOI': '10.1007/s00392-020-01626-9', 'author': 'B Li', 'doi-asserted-by': 'publisher', 'first-page': '531', 'journal-title': 'Clin Res Cardiol', 'key': '9858_CR25', 'unstructured': 'Li B, Yang J, Zhao F et al (2020) Prevalence and impact of ' 'cardiovascular metabolic diseases on COVID-19 in China. Clin Res Cardiol ' '109:531–538. https://doi.org/10.1007/s00392-020-01626-9', 'volume': '109', 'year': '2020'}, { 'key': '9858_CR26', 'unstructured': 'Kamkin E et al. (2020) Interim guidelines for the prevention, diagnosis ' 'and treatment of new coronaviral infection (COVID-19). ' 'https://static-0.minzdrav.gov.ru/system/attachments/attaches/000/051/777/original/030902020_COVID-19_v8.pdf. ' 'Accessed 03 Sept\xa02020'}, { 'DOI': '10.4081/itjm.2020.1185', 'author': 'V Ivashkin', 'doi-asserted-by': 'publisher', 'first-page': '1', 'journal-title': 'Ital J Med', 'key': '9858_CR27', 'unstructured': 'Ivashkin V, Fadeeva M, Skhirtladze M et al (2020) Intestinal microbiota ' 'in the pathogenesis of chronic heart failure. Ital J Med 14:1–8. ' 'https://doi.org/10.4081/itjm.2020.1185', 'volume': '14', 'year': '2020'}, { 'DOI': '10.1111/apt.13404', 'author': 'H Szajewska', 'doi-asserted-by': 'publisher', 'first-page': '1149', 'journal-title': 'Aliment Pharmacol Ther', 'key': '9858_CR28', 'unstructured': 'Szajewska H, Kołodziej M (2015) Systematic review with meta-analysis: ' 'Lactobacillus rhamnosus GG in the prevention of antibiotic-associated ' 'diarrhoea in children and adults. Aliment Pharmacol Ther 42:1149–1157. ' 'https://doi.org/10.1111/apt.13404', 'volume': '42', 'year': '2015'}, { 'DOI': '10.3748/wjg.v25.i33.4999', 'author': 'YT Li', 'doi-asserted-by': 'publisher', 'first-page': '4999', 'journal-title': 'World J Gastroenterol', 'key': '9858_CR29', 'unstructured': 'Li YT, Xu H, Ye JZ (2019) Efficacy of Lactobacillus rhamnosus GG in ' 'treatment of acute pediatric diarrhea: a systematic review with ' 'meta-analysis. World J Gastroenterol 25:4999–5016. ' 'https://doi.org/10.3748/wjg.v25.i33.4999', 'volume': '25', 'year': '2019'}, { 'DOI': '10.26355/eurrev_202009_23057', 'doi-asserted-by': 'publisher', 'key': '9858_CR30', 'unstructured': 'Di JB, Gai ZT (2020) Protective efficacy of probiotics on the treatment ' 'of acute rotavirus diarrhea in children: an updated meta-analysis. Eur ' 'Rev Med Pharmacol Sci 24:9675–9683. ' 'https://doi.org/10.26355/eurrev_202009_23057'}, { 'DOI': '10.3389/fbioe.2020.01024', 'author': 'P Rasinkangas', 'doi-asserted-by': 'publisher', 'first-page': '1024', 'journal-title': 'Front Bioeng Biotechnol', 'key': '9858_CR31', 'unstructured': 'Rasinkangas P, Tytgat HLP, Ritari J et al (2020) Characterization of ' 'highly mucus-adherent non-GMO derivatives of Lacticaseibacillus ' 'rhamnosus GG. Front Bioeng Biotechnol 8:1024. ' 'https://doi.org/10.3389/fbioe.2020.01024', 'volume': '8', 'year': '2020'}, { 'DOI': '10.3389/fmicb.2016.00738', 'author': 'L Valdés-Varela', 'doi-asserted-by': 'publisher', 'first-page': '738', 'journal-title': 'Front Microbiol', 'key': '9858_CR32', 'unstructured': 'Valdés-Varela L, Hernández-Barranco AM, Ruas-Madiedo P, Gueimonde M ' '(2016) Effect of Bifidobacterium upon Clostridium difficile growth and ' 'toxicity when co-cultured in different prebiotic substrates. Front ' 'Microbiol 7:738. https://doi.org/10.3389/fmicb.2016.00738', 'volume': '7', 'year': '2016'}, { 'DOI': '10.1371/journal.pone.0173979', 'author': 'T Kawahara', 'doi-asserted-by': 'publisher', 'journal-title': 'PLoS ONE', 'key': '9858_CR33', 'unstructured': 'Kawahara T, Makizaki Y, Oikawa Y et al (2017) Oral administration of ' 'Bifidobacterium bifidum G9–1 alleviates rotavirus gastroenteritis ' 'through regulation of intestinal homeostasis by inducing mucosal ' 'protective factors. PLoS One 12:e0173979. ' 'https://doi.org/10.1371/journal.pone.0173979', 'volume': '12', 'year': '2017'}, { 'DOI': '10.1152/ajpcell.00194.2014', 'author': 'A Kumar', 'doi-asserted-by': 'publisher', 'first-page': 'C1084', 'journal-title': 'Am J Physiol Cell Physiol', 'key': '9858_CR34', 'unstructured': 'Kumar A, Hecht C, Priyamvada S (2014) Probiotic Bifidobacterium species ' 'stimulate human SLC26A3 gene function and expression in intestinal ' 'epithelial cells. Am J Physiol Cell Physiol 307:C1084–C1092. ' 'https://doi.org/10.1152/ajpcell.00194.2014', 'volume': '307', 'year': '2014'}], 'reference-count': 34, 'references-count': 34, 'relation': {}, 'resource': {'primary': {'URL': 'https://link.springer.com/10.1007/s12602-021-09858-5'}}, 'score': 1, 'short-title': [], 'source': 'Crossref', 'subject': ['Molecular Biology', 'Molecular Medicine', 'Microbiology'], 'subtitle': [], 'title': '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', 'type': 'journal-article', 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'volume': '15'}
Late treatment
is less effective
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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