Probiotics for Long COVID Symptoms

Overseen By

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical College of Wisconsin

Must not be taking: Vitamin K antagonists

Disqualifiers: Antibiotics, Chronic diseases, Cognitive impairment, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the probiotic Lp299v can reduce symptoms of Long COVID, focusing on blood vessel function and inflammation. Participants will take either the probiotic or a placebo daily for eight weeks. Individuals diagnosed with Long COVID, who are 30-180 days post-COVID, and have not recently taken antibiotics may qualify for this trial. The researchers aim to determine if the probiotic improves health by reducing inflammation and enhancing blood vessel health. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research on Long COVID treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking antibiotics, Vitamin K antagonists like coumadin or warfarin, or if you have certain health conditions. It's best to discuss your medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that Lactobacillus plantarum 299v (Lp299v), the probiotic under testing, has beneficial effects on the gut. Individuals who have taken Lp299v report improved gut health, including less gas and more regular bowel movements, suggesting that Lp299v is generally well-tolerated.

One study found that Lp299v does not cause serious side effects like stomach pain or bloating compared to a placebo. It is important to note that Lp299v is considered safe for most people, though it may not be suitable for those with weakened immune systems or certain health conditions.

Overall, current evidence supports the safety of Lp299v for human use, particularly for gut health. This makes it a promising option for those considering participation in the trial for Long COVID symptoms. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for Long COVID, which often focus on managing symptoms with medications like anti-inflammatories or anticoagulants, Lp299v is a probiotic that aims to address symptoms by improving gut health. Researchers are excited about Lp299v because it introduces 20 billion colony-forming units of beneficial bacteria to the gut, which could help rebalance the microbiome and reduce inflammation. This unique approach could provide relief without relying on traditional pharmaceuticals, offering a more natural option for those suffering from Long COVID symptoms.

What evidence suggests that Lp299v might be an effective treatment for Long COVID?

Research suggests that the probiotic Lactobacillus plantarum 299v (Lp299v), which participants in this trial may receive, may help with Long COVID symptoms. Studies have shown that Lp299v can improve blood vessel function and reduce inflammation, common issues in Long COVID. This probiotic lowers certain DNA fragments in the blood linked to inflammation. It also reduces the activity of toll-like receptor 9, a part of the immune system, and decreases inflammation markers like interleukin-6. These changes might improve blood flow and make blood vessels less stiff, potentially relieving some Long COVID symptoms. ^{6 7 8 9 10}

Who Is on the Research Team?

Michael E Widlansky

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

This trial is for adults aged 18-89 who have had COVID-19 and are experiencing lingering symptoms known as PASC. They must be within 30 to 180 days post-diagnosis. People with daily alcohol use, recent antibiotics, blood thinner usage like warfarin, pregnancy, cognitive issues preventing study compliance, unstable heart disease or certain chronic conditions can't participate.

Inclusion Criteria

I was diagnosed with COVID-19 between 30 to 180 days ago.

I have been diagnosed with long COVID by a doctor.

Exclusion Criteria

Pregnant at the time of screening

You drink alcohol every day, which could affect the way the study drug works.

I am currently taking blood thinners like coumadin or warfarin.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Lp299v or placebo supplementation for 8 weeks

8 weeks

Weekly visits (in-person or virtual) for monitoring and data collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lp299v

Trial Overview

The trial tests if a probiotic called Lactobacillus plantarum (Lp299v) in capsule form can improve blood vessel function in those with PASC by reducing inflammation and immune system activation compared to a placebo made of potato starch capsules.

How Is the Trial Designed?

Group I: Lp299v Experimental Treatment 1 Intervention

Subjects will consume 20 billion colony forming units of Lp299v (2 capsules) once daily for 8 weeks.

Group II: Heat-killed placebo control Placebo Group 1 Intervention

Subjects will consume potato starch (2 capsules) once daily for 8 weeks.

Lp299v is already approved in European Union, United States for the following indications:

Approved in European Union as LP299V for:

• Gastrointestinal health
• Irritable bowel syndrome (IBS)
• Iron absorption and status

Approved in United States as LP299V for:

• Gastrointestinal health
• Irritable bowel syndrome (IBS)
• Iron absorption and status
• Post-Acute Sequelae of SARS-CoV-2 (PASC)

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Published Research Related to This Trial

The study found that the probiotic Lactobacillus plantarum significantly increased the innate cytokine index in healthy individuals, suggesting it may enhance immune responses against COVID-19, with a mean fold change of 17-fold (P=0.0138).

In contrast, another probiotic, Bifidobacterium longum, did not show a significant effect on the innate cytokine index, indicating that not all probiotics have the same immunomodulatory potential against COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactobacillus plantarum induces innate cytokine responses that potentially provide a protective benefit against COVID-19: A single-arm, double-blind, prospective trial combined with an in vitro cytokine response assay. Kageyama, Y., Nishizaki, Y., Aida, K., et al.[2021]

The probiotic Lactobacillus plantarum GUANKE (LPG) can enhance immune responses to SARS-CoV-2 vaccines, promoting the production of neutralizing antibodies even 6 months post-vaccination.

Administering LPG immediately after vaccination significantly boosts antibody levels and maintains T-cell responses in both the lungs and spleen, suggesting it could be an effective strategy to prolong vaccine-induced immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Boosting Vaccine-Elicited Respiratory Mucosal and Systemic COVID-19 Immunity in Mice With the Oral Lactobacillus plantarum. Xu, J., Ren, Z., Cao, K., et al.[2022]

In a study of 35 cancer patients receiving home enteral nutrition, Lactobacillus plantarum 299v (Lp299v) significantly increased serum albumin levels compared to a placebo, indicating potential benefits for nutritional status.

Lp299v also reduced gastrointestinal symptoms like vomiting and flatulence after 4 weeks, suggesting it may help alleviate discomfort associated with enteral nutrition, although it did not significantly improve overall quality of life compared to the placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of 4 weeks of Lactobacillus plantarum 299v supplementation on nutritional status, enteral nutrition tolerance, and quality of life in cancer patients receiving home enteral nutrition - a double-blind, randomized, and placebo-controlled trial. Kaźmierczak-Siedlecka, K., Folwarski, M., Ruszkowski, J., et al.[2021]

Lactiplantibacillus plantarum 299v (L. plantarum 299v) is a well-researched probiotic strain with over 170 publications, including more than 60 clinical studies, demonstrating its safety and efficacy in improving gastrointestinal health, particularly in reducing symptoms of irritable bowel syndrome (IBS).

This strain not only enhances iron absorption and status but also survives the harsh conditions of the gastrointestinal tract, making it suitable for various food applications and dietary supplements, with a stable shelf-life in freeze-dried formats.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactiplantibacillus plantarum 299v (LP299V®): three decades of research. Nordström, EA., Teixeira, C., Montelius, C., et al.[2021]

In a study of 3533 hospitalized patients, the routine use of the probiotic Lactobacillus plantarum 299v (LP299v) significantly reduced the incidence of Clostridium difficile infections (CDI) from 1.21% to 0.11% after its implementation as a preventive measure during antibiotic treatment.

The findings suggest that LP299v may be an effective prophylactic option for preventing CDI in high-risk patients receiving antibiotics, particularly in nephrology and transplantation settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Lactobacillus plantarum 299v on the Incidence of Clostridium difficile Infection in High Risk Patients Treated with Antibiotics. Kujawa-Szewieczek, A., Adamczak, M., Kwiecień, K., et al.[2020]

In a study of 120 patients with mild COVID-19, those taking a spore-based Bacillus probiotic showed a significantly shorter time to symptom resolution (6.63 days) compared to those not taking probiotics (8.48 days).

Patients on probiotics also experienced faster fever resolution and reported fewer digestive symptoms, indicating that ongoing probiotic treatment may improve clinical outcomes in mild COVID-19 cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ongoing Treatment with a Spore-Based Probiotic Containing Five Strains of Bacillus Improves Outcomes of Mild COVID-19. Catinean, A., Sida, A., Silvestru, C., et al.[2023]

Immunomodulatory strains of Lactiplantibacillus plantarum, particularly MPL16, have been shown to enhance the immune response in human respiratory cells and increase resistance to SARS-CoV-2 infection, indicating potential therapeutic benefits against COVID-19.

This study is the first to demonstrate that specific immunobiotic lactobacilli can positively influence the replication of SARS-CoV-2, suggesting a new avenue for research into probiotics as a preventive or therapeutic strategy for COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunobiotic Lactobacilli Improve Resistance of Respiratory Epithelial Cells to SARS-CoV-2 Infection. Islam, MA., Albarracin, L., Tomokiyo, M., et al.[2021]

The probiotic strain Lacticaseibacillus paracasei DG has shown significant potential in enhancing antiviral immunity and inhibiting SARS-CoV-2 infection in laboratory studies using intestinal epithelial cells.

L. paracasei DG not only directly inhibits SARS-CoV-2 but also boosts the antiviral effects of lactoferrin, suggesting it could be an effective preventive measure against COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lacticaseibacillus paracasei DG enhances the lactoferrin anti-SARS-CoV-2 response in Caco-2 cells. Salaris, C., Scarpa, M., Elli, M., et al.[2021]

Lactobacillus plantarum 299v has been shown to improve gut health by increasing anti-inflammatory cytokines, which can enhance cancer treatment efficacy and reduce gastrointestinal side effects.

This probiotic also benefits patients with irritable bowel syndrome (IBS) by normalizing stool and alleviating abdominal pain, and it helps prevent Clostridium difficile-associated diarrhea in those undergoing antibiotic treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of Lactobacillus plantarum 299v in supporting treatment of selected diseases. Kaźmierczak-Siedlecka, K., Daca, A., Folwarski, M., et al.[2021]

In a study using a rat model of colitis, Lactobacillus plantarum species 299 (LP299) did not improve the severity of colitis or gut permeability compared to untreated controls, indicating it may not be effective in this context.

The experiment involved 48 rats with induced colitis and assessed outcomes like colon macroscopic scoring and gut permeability, but LP299 treatment did not show any beneficial effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotic therapy fails to improve gut permeability in a hapten model of colitis. Kennedy, RJ., Hoper, M., Deodhar, K., et al.[2019]

In a study of 300 symptomatic COVID-19 outpatients, those taking a specific probiotic formula achieved complete remission of symptoms at a significantly higher rate (53.1%) compared to the placebo group (28.1%), indicating the probiotic's potential efficacy in managing COVID-19 symptoms.

The probiotic supplementation was well-tolerated and not only reduced viral load and lung infiltrates but also increased specific immune responses against SARS-CoV-2, suggesting that its mechanism of action may involve enhancing the host's immune system rather than altering gut microbiota composition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial. Gutiérrez-Castrellón, P., Gandara-Martí, T., Abreu Y Abreu, AT., et al.[2023]

In a study of 44 moderate/severe COVID-19 inpatients, those who received an oral booster of single-strain probiotic bifidobacteria had a significantly shorter hospital stay (median of 7.6 days) compared to those who did not receive the probiotic.

The probiotic group also showed improved clinical outcomes, including better radiological improvement and lower levels of interleukin-6, with a mortality rate of 5% compared to 25% in the non-probiotic group, suggesting that probiotics may enhance recovery in severe COVID-19 cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral booster probiotic bifidobacteria in SARS-COV-2 patients. Bozkurt, HS., Bilen, Ö.[2022]

In a study involving 200 nursing home residents over 60 years old, the probiotic Loigolactobacillus coryniformis K8 did not show a significant difference in overall antibody levels compared to a placebo after COVID-19 vaccination.

However, among those who contracted COVID-19, participants taking K8 had significantly higher IgG antibody levels, suggesting that K8 may enhance the immune response in elderly individuals, particularly in those over 85 years old.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Loigolactobacillus coryniformis K8 CECT 5711 on the Immune Response of Elderly Subjects to COVID-19 Vaccination: A Randomized Controlled Trial. Fernández-Ferreiro, A., Formigo-Couceiro, FJ., Veiga-Gutierrez, R., et al.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11011397/

Long COVID: Long-Term Impact of SARS-CoV2 - PMC

Malik and colleagues showed that Lactobacillus Plantarum 299v supplementation improved vascular endothelial function and reduced inflammatory ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05227170

Impact of Lp299v on Vascular Function in Patients With ...

Based on these data, the investigators hypothesize that supplementation with Lp299v will attenuate SARS-CoV-2 associated endothelial dysfunction by reducing cf ...

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S2213453022002373

Modulatory effects of Lactiplantibacillus plantarum on ...

L. plantarum also has been shown to prevent and treat upper respiratory tract infections by inducing immunomodulatory and anti-inflammatory effects while ...

4.

tandfonline.com

tandfonline.com/doi/full/10.1080/25785826.2025.2570902

Long COVID: mechanisms of disease, multisystem ...

Persistent symptoms after SARS-CoV-2 infection may be partly explained by incomplete viral clearance, a mechanism also observed with other ...

5.

mdpi.com

mdpi.com/1420-3049/30/20/4130

The Role of Probiotics and Their Postbiotic Metabolites in ...

Many of patients who have survived the acute phase of SARS-CoV-2 infection experience long-term symptoms, collectively known as “post-acute COVID-19 syndrome” ...

6.

sciencedirect.com

sciencedirect.com/science/article/pii/S0753332225000496

Subphenotypes of Long COVID and the clinical ...

plantarum 299 v. Consuming the probiotic was linked to a decrease in flatulence, a return to normal bowel movement rhythm, and a significant improvement in all ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11990516/

Strain-Specific Therapeutic Potential of Lactiplantibacillus ...

In contrast, L. plantarum 299v [33,38] showed no significant effect on abdominal pain, bloating, or rectal emptying when compared to a placebo. ...

8.

mdpi.com

mdpi.com/2072-6643/15/15/3466

Intake of Lactiplantibacillus plantarum HEAL9 Improves ...

Intake of LPHEAL9 significantly improved cognitive functions compared to the placebo, potentially by ameliorating aspects of mood and sleep.

9.

webmd.com

webmd.com/vitamins/ai/ingredientmono-1672/lactiplantibacillus-plantarum

Lactiplantibacillus Plantarum - Uses, Side Effects, and More

There is also no good evidence to support using L. plantarum for COVID-19. Don't confuse L. plantarum with other probiotics, or with fermented food products ...

10.

fda.gov

fda.gov/media/178866/download

GRAS Notice (GRN) 1127, Lactiplantibacillus plantarum ...

It is not intended to be used by certain individuals under medical supervision, including immune- compromised individuals, infants with marked ...