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
Keywords:
Probiotics, Colchicine, COVID-19, RCT, Ain Shams University, Cairo
Abstract
Background: Coronavirus disease 2019 (COVID-19) is a newly emerging human disease caused by a novel coronavirus, causing a global pandemic crisis. Probiotics and/or colchicine may be considered as options for treatment since they have anti-viral, anti-inflammatory, and immunomodulatory effects. Objective: To assess the effectiveness of probiotic supplements (Lactobacillus acidophilus) and colchicine on symptoms, duration, and progression of mild and moderate cases of COVID-19 infection. Methods: A three-arm randomized controlled clinical trial was carried out in the triage clinic of the family medicine department at Ain Shams University Hospitals on 150 participants who had been diagnosed as COVID-19 patients with mild and moderate severity. Patients aged below 18 years or above 65 years with any co-morbidities, pregnant or lactating females, and severe COVID-19 confirmed cases were excluded. Randomization was done by using sealed envelopes containing codes for intervention or control. Patients are followed up for improvement of their symptoms with no development of new symptoms over the course of two weeks. Results: A total of 150 patients with mild and moderate severity of COVID-19 were enrolled in the study, 50 patients in each arm; around one third (34.7%) of the participants were aged between 29 and 39 years; one-quarter (24.7%) were aged between 18 and 28 years and 40.6% were aged 40 years and above. The mean duration of symptoms improvement was 12, 11 and 12 in the colchicine, probiotic, and control groups, respectively. Improvement of inflammatory markers over time occurred in each of the three groups, with no statistically significant difference between them. Conclusion: Probiotic Lactobacillus acidophilus and colchicine shows no significant effect on the symptoms, duration, and progression of mild and moderate cases of COVID-19.
Trial registration: The study was registered at Protocol Registration and Results System (No. NCT05911022) registered on 20/06/2023. https://classic.clinicaltrials.gov/ct2/show/NCT05911022
References
1. World Health Organization. Coronavirus disease (covid-19) - events as they happen .Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/events-as-they-happen (Accessed on April 29, 2023).
2. Centres for Disease Control and Prevention. "Coronavirus disease 2019 (COVID‐19) 2021 case definition. Available from: https://ndc.services.cdc.gov/case-definitions/coronavirus-disease-2019-2021/ (Accessed on April 29, 2023).
3. Angurana SK, Bansal A. Coronavirus disease 2019: think about the link. Br J Nutr 2021;126(10):1564-70. doi: 10.1017/S000711452000361X.
4. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S, Calder PC, Sanders ME. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 2014;11(8):506-14. doi: 10.1038/nrgastro.2014.66.
5. Yeo C, Kaushal S, Yeo D. Enteric involvement of coronaviruses: Is faecal-oral transmission of SARS-CoV-2 possible? Lancet Gastroenterol Hepatol 2020;5(4):335-7. doi: 10.1016/S2468-1253(20)30048-0.
6. Effenberger M, Grabherr F, Mayr L, Schwaerzler J, Nairz M, Seifert M, Hilbe R, Seiwald S, Scholl-Buergi S, Fritsche G, Bellmann-Weiler R, Weiss G, Müller T, Adolph TE, Tilg H. Faecal calprotectin indicates intestinal inflammation in COVID-19. Gut 2020;69(8):1543-4. doi: 10.1136/gutjnl-2020-321388.
7. Zhang H, Yeh C, Jin Z, Ding L, Liu BY, Zhang L, Dannelly HK. Prospective study of probiotic supplementation results in immune stimulation and improvement of upper respiratory infection rate. Synth Syst Biotechnol 2018;3(2):113-20. doi: 10.1016/j.synbio.2018.03.001.
8. Zuo T, Zhang F, Lui GCY, Yeoh YK, Li AYL, Zhan H, et al. Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization. Gastroenterology 2020;159(3):944-55.e8. doi: 10.1053/j.gastro.2020.05.048.
9. Lopes MI, Bonjorno LP, Giannini MC, Amaral NB, Menezes PI, Dib SM, et al. Beneficial effects of colchicine for moderate to severe COVID-19: a randomised, double-blinded, placebo-controlled clinical trial. RMD Open 2021;7(1):e001455. doi: 10.1136/rmdopen-2020-001455.
10. Leung YY, Yao Hui LL, Kraus VB. Colchicine-Update on mechanisms of action and therapeutic uses. Semin Arthritis Rheum 2015;45(3):341-50. doi: 10.1016/j.semarthrit.2015.06.013.
11. Tardif J-C, Bouabdallaoui N, L'Allier PL, Gaudet D, Shah B, Pillinger MH, et al. Colchicine for community-treated patients with COVID-19 (COLCORONA): a phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial. Lancet Respir Med 2021;9(8):924-32. doi: 10.1016/S2213-2600(21)00222-8.
12. Siemieniuk RAC, Bartoszko JJ, Zeraatkar D, Kum E, Qasim A, Díaz Martinez JP, et al. Drug treatments for covid-19: living systematic review and network meta-analysis. BMJ 2020;370:m2980. doi: 10.1136/bmj.m2980.
13. Karatza E, Ismailos G, Karalis V. Colchicine for the treatment of COVID-19 patients: efficacy, safety, and model informed dosage regimens. Xenobiotica. 2021;51(6):643-56. doi: 10.1080/00498254.2021.
14. Teranaka W, Pan D. Discharge criteria for patients with COVID-19 to long-term care facilities requires modification. Clin Med (Lond) 2021;21(1):e116-e117. doi: 10.7861/clinmed. Let.21.1.2.
15. Doerre A, Doblhammer G. The influence of gender on COVID-19 infections and mortality in Germany: Insights from age- and gender-specific modeling of contact rates, infections, and deaths in the early phase of the pandemic. PLoS One 2022;17(5):e0268119. doi: 10.1371/journal.pone.0268119.
16. Farsalinos K, Bagos PG, Giannouchos T, Niaura R, Barbouni A, Poulas K. Smoking prevalence among hospitalized COVID-19 patients and its association with disease severity and mortality: an expanded re-analysis of a recent publication. Harm Reduct J 2021;18(1):9. doi: 10.1186/s12954-020-00437-5.
17. Hakki S, Zhou J, Jonnerby J, Singanayagam A, Barnett JL, Madon KJ, et al. Onset and window of SARS-CoV-2 infectiousness and temporal correlation with symptom onset: a prospective, longitudinal, community cohort study. Lancet Respir Med 2022;10(11):1061-73. doi: 10.1016/S2213-2600(22)00226-0.
18. Gorial FI, Maulood MF, Abdulamir AS, Alnuaimi AS, abdulrrazaq MK, Bonyan FA. Randomized controlled trial of colchicine add on to the standard therapy in moderate and severe corona virus Disease-19 infection. Ann Med Surg (Lond) 2022;77:103593. doi: 10.1016/j.amsu.2022.103593.
19. Dorward J, Yu L-M, Hayward G, Saville BR, Gbinigie O, Van Hecke O, et al. Colchicine for COVID-19 in the community (PRINCIPLE): a randomised, controlled, adaptive platform trial. Br J Gen Pract 2022;72(720):e446-e455. doi: 10.3399/BJGP.2022.0083.
20. Colchicine in patients admitted to hospital with covid-19 (recovery): Colchicine in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet Respir Med 2021;9(12):1419-26. doi: 10.1016/S2213-2600(21)00435-5.
21. Hariyanto TI, Halim DA, Jodhinata C, Yanto TA, Kurniawan A. Colchicine treatment can improve outcomes of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis. Clin Exp Pharmacol Physiol 2021;48(6):823-30. doi: 10.1111/1440-1681.13488.
22. AbdelFattah EB, Korra EEA, Ahmed MA. Use of colchicine in COVID-19 hospitalized patients. Egypt J Chest Dis Tuberc 2022;71:290-5. doi: 10.4103/ecdt.ecdt_59_21.
23. Terkeltaub RA, Furst DE, Bennett K, Kook KA, Crockett RS, Davis MW. High versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study. Arthritis Rheum 2010;62(4):1060-8. doi: 10.1002/art.27327.
24. Yasmin F, Najeeb H, Moeed A, Hassan W, Khatri M, Asghar MS, et al. Safety and efficacy of colchicine in COVID-19 patients: A systematic review and meta-analysis of randomized control trials. PLoS One 2022;17(4):e0266245. doi: 10.1371/journal.pone.0266245.
25. Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, Tian DS. Dysregulation of Immune Response in Patients with Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis 2020;71(15):762-8. doi: 10.1093/cid/ciaa248.
26. Soraya GV, Ulhaq ZS. Crucial laboratory parameters in COVID-19 diagnosis and prognosis: An updated meta-analysis. Med Clin (Barc) 2020;155(4):143-51. doi: 10.1016/j.medcli.2020.05.017.
27. Deftereos SG, Giannopoulos G, Vrachatis DA, Siasos GD, Giotaki SG, Gargalianos P, et al. Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized with Coronavirus Disease 2019: The GRECCO-19 Randomized Clinical Trial. JAMA Netw Open 2020;3(6):e2013136. doi: 10.1001/jamanetworkopen.2020.13136.
28. Sarwar M, Ali Z, Fatima M, Sarfraz Z, Sarfraz A, Cherrez‐Ojeda I. Colchicine, COVID-19, and hematological parameters: A meta-analysis. J Clin Lab Anal 2021;35(12): e24057. doi: 10.1002/jcla.24057.
29. Sandhu T, Tieng A, Chilimuri S, Franchin G. Case Control Study to Evaluate the Impact of Colchicine on Patients Admitted to the Hospital with Moderate to Severe COVID-19 Infection. Can J Infect Dis Med Microbiol 2020;2020:8865954. doi: 10.1155/2020/8865954.
30. Wischmeyer PE, Tang H, Ren Y, Bohannon L, Ramirez ZE, Andermann TM, Sung AD. Daily Lactobacillus probiotic versus placebo in COVID-19-exposed household contacts (PROTECT-EHC): a randomized clinical trial. MedRxiv 2022-01. doi: 10.1101/2022.01.04.21268275
31. Darbandi A, Asadi A, Ghanavati R, Afifirad R, Darb Emamie A, kakanj M, et al. The effect of probiotics on respiratory tract infection with special emphasis on COVID-19: Systemic review 2010-20. Int J Infect Dis 2021; 105:91-104. doi: 10.1016/j.ijid.2021.02.011.
2. Centres for Disease Control and Prevention. "Coronavirus disease 2019 (COVID‐19) 2021 case definition. Available from: https://ndc.services.cdc.gov/case-definitions/coronavirus-disease-2019-2021/ (Accessed on April 29, 2023).
3. Angurana SK, Bansal A. Coronavirus disease 2019: think about the link. Br J Nutr 2021;126(10):1564-70. doi: 10.1017/S000711452000361X.
4. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S, Calder PC, Sanders ME. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 2014;11(8):506-14. doi: 10.1038/nrgastro.2014.66.
5. Yeo C, Kaushal S, Yeo D. Enteric involvement of coronaviruses: Is faecal-oral transmission of SARS-CoV-2 possible? Lancet Gastroenterol Hepatol 2020;5(4):335-7. doi: 10.1016/S2468-1253(20)30048-0.
6. Effenberger M, Grabherr F, Mayr L, Schwaerzler J, Nairz M, Seifert M, Hilbe R, Seiwald S, Scholl-Buergi S, Fritsche G, Bellmann-Weiler R, Weiss G, Müller T, Adolph TE, Tilg H. Faecal calprotectin indicates intestinal inflammation in COVID-19. Gut 2020;69(8):1543-4. doi: 10.1136/gutjnl-2020-321388.
7. Zhang H, Yeh C, Jin Z, Ding L, Liu BY, Zhang L, Dannelly HK. Prospective study of probiotic supplementation results in immune stimulation and improvement of upper respiratory infection rate. Synth Syst Biotechnol 2018;3(2):113-20. doi: 10.1016/j.synbio.2018.03.001.
8. Zuo T, Zhang F, Lui GCY, Yeoh YK, Li AYL, Zhan H, et al. Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization. Gastroenterology 2020;159(3):944-55.e8. doi: 10.1053/j.gastro.2020.05.048.
9. Lopes MI, Bonjorno LP, Giannini MC, Amaral NB, Menezes PI, Dib SM, et al. Beneficial effects of colchicine for moderate to severe COVID-19: a randomised, double-blinded, placebo-controlled clinical trial. RMD Open 2021;7(1):e001455. doi: 10.1136/rmdopen-2020-001455.
10. Leung YY, Yao Hui LL, Kraus VB. Colchicine-Update on mechanisms of action and therapeutic uses. Semin Arthritis Rheum 2015;45(3):341-50. doi: 10.1016/j.semarthrit.2015.06.013.
11. Tardif J-C, Bouabdallaoui N, L'Allier PL, Gaudet D, Shah B, Pillinger MH, et al. Colchicine for community-treated patients with COVID-19 (COLCORONA): a phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial. Lancet Respir Med 2021;9(8):924-32. doi: 10.1016/S2213-2600(21)00222-8.
12. Siemieniuk RAC, Bartoszko JJ, Zeraatkar D, Kum E, Qasim A, Díaz Martinez JP, et al. Drug treatments for covid-19: living systematic review and network meta-analysis. BMJ 2020;370:m2980. doi: 10.1136/bmj.m2980.
13. Karatza E, Ismailos G, Karalis V. Colchicine for the treatment of COVID-19 patients: efficacy, safety, and model informed dosage regimens. Xenobiotica. 2021;51(6):643-56. doi: 10.1080/00498254.2021.
14. Teranaka W, Pan D. Discharge criteria for patients with COVID-19 to long-term care facilities requires modification. Clin Med (Lond) 2021;21(1):e116-e117. doi: 10.7861/clinmed. Let.21.1.2.
15. Doerre A, Doblhammer G. The influence of gender on COVID-19 infections and mortality in Germany: Insights from age- and gender-specific modeling of contact rates, infections, and deaths in the early phase of the pandemic. PLoS One 2022;17(5):e0268119. doi: 10.1371/journal.pone.0268119.
16. Farsalinos K, Bagos PG, Giannouchos T, Niaura R, Barbouni A, Poulas K. Smoking prevalence among hospitalized COVID-19 patients and its association with disease severity and mortality: an expanded re-analysis of a recent publication. Harm Reduct J 2021;18(1):9. doi: 10.1186/s12954-020-00437-5.
17. Hakki S, Zhou J, Jonnerby J, Singanayagam A, Barnett JL, Madon KJ, et al. Onset and window of SARS-CoV-2 infectiousness and temporal correlation with symptom onset: a prospective, longitudinal, community cohort study. Lancet Respir Med 2022;10(11):1061-73. doi: 10.1016/S2213-2600(22)00226-0.
18. Gorial FI, Maulood MF, Abdulamir AS, Alnuaimi AS, abdulrrazaq MK, Bonyan FA. Randomized controlled trial of colchicine add on to the standard therapy in moderate and severe corona virus Disease-19 infection. Ann Med Surg (Lond) 2022;77:103593. doi: 10.1016/j.amsu.2022.103593.
19. Dorward J, Yu L-M, Hayward G, Saville BR, Gbinigie O, Van Hecke O, et al. Colchicine for COVID-19 in the community (PRINCIPLE): a randomised, controlled, adaptive platform trial. Br J Gen Pract 2022;72(720):e446-e455. doi: 10.3399/BJGP.2022.0083.
20. Colchicine in patients admitted to hospital with covid-19 (recovery): Colchicine in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet Respir Med 2021;9(12):1419-26. doi: 10.1016/S2213-2600(21)00435-5.
21. Hariyanto TI, Halim DA, Jodhinata C, Yanto TA, Kurniawan A. Colchicine treatment can improve outcomes of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis. Clin Exp Pharmacol Physiol 2021;48(6):823-30. doi: 10.1111/1440-1681.13488.
22. AbdelFattah EB, Korra EEA, Ahmed MA. Use of colchicine in COVID-19 hospitalized patients. Egypt J Chest Dis Tuberc 2022;71:290-5. doi: 10.4103/ecdt.ecdt_59_21.
23. Terkeltaub RA, Furst DE, Bennett K, Kook KA, Crockett RS, Davis MW. High versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study. Arthritis Rheum 2010;62(4):1060-8. doi: 10.1002/art.27327.
24. Yasmin F, Najeeb H, Moeed A, Hassan W, Khatri M, Asghar MS, et al. Safety and efficacy of colchicine in COVID-19 patients: A systematic review and meta-analysis of randomized control trials. PLoS One 2022;17(4):e0266245. doi: 10.1371/journal.pone.0266245.
25. Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, Tian DS. Dysregulation of Immune Response in Patients with Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis 2020;71(15):762-8. doi: 10.1093/cid/ciaa248.
26. Soraya GV, Ulhaq ZS. Crucial laboratory parameters in COVID-19 diagnosis and prognosis: An updated meta-analysis. Med Clin (Barc) 2020;155(4):143-51. doi: 10.1016/j.medcli.2020.05.017.
27. Deftereos SG, Giannopoulos G, Vrachatis DA, Siasos GD, Giotaki SG, Gargalianos P, et al. Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized with Coronavirus Disease 2019: The GRECCO-19 Randomized Clinical Trial. JAMA Netw Open 2020;3(6):e2013136. doi: 10.1001/jamanetworkopen.2020.13136.
28. Sarwar M, Ali Z, Fatima M, Sarfraz Z, Sarfraz A, Cherrez‐Ojeda I. Colchicine, COVID-19, and hematological parameters: A meta-analysis. J Clin Lab Anal 2021;35(12): e24057. doi: 10.1002/jcla.24057.
29. Sandhu T, Tieng A, Chilimuri S, Franchin G. Case Control Study to Evaluate the Impact of Colchicine on Patients Admitted to the Hospital with Moderate to Severe COVID-19 Infection. Can J Infect Dis Med Microbiol 2020;2020:8865954. doi: 10.1155/2020/8865954.
30. Wischmeyer PE, Tang H, Ren Y, Bohannon L, Ramirez ZE, Andermann TM, Sung AD. Daily Lactobacillus probiotic versus placebo in COVID-19-exposed household contacts (PROTECT-EHC): a randomized clinical trial. MedRxiv 2022-01. doi: 10.1101/2022.01.04.21268275
31. Darbandi A, Asadi A, Ghanavati R, Afifirad R, Darb Emamie A, kakanj M, et al. The effect of probiotics on respiratory tract infection with special emphasis on COVID-19: Systemic review 2010-20. Int J Infect Dis 2021; 105:91-104. doi: 10.1016/j.ijid.2021.02.011.
Published
2024-01-10
How to Cite
Mrs. Wedad Mohammad. (2024). 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. Central Asian Journal of Medical and Natural Science, 5(1), 72-84. Retrieved from https://cajmns.centralasianstudies.org/index.php/CAJMNS/article/view/2282
Section
Articles
