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

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• It is advisable for those over 60 years old with a metabolic risk factor (BMI>30, diabetes and/or hypertension) to consult with their clinical practitioners if tested positive for Covid-19.
• Specific probiotic strains are reported to show positive results in reducing the duration and severity of Covid-19 symptoms in adults under 60 years old.
• These probiotics (Lactiplantibacillus plantarum KABP022, KABP023, and KAPB033, plus strain Pediococcus acidilactici KABP021) have also shown a positive effect on reducing inflammation and supporting remission of Covid-19.

A quadruple-blinded, randomized trial was conducted in adults with symptomatic Coronavirus Disease 2019(Covid19) outpatients.

Three hundred subjects between the ages of 18 and 60 years, with a peripheral oxygen saturation (SpO2) ≥ 90% and in whom 42% had known metabolic risk factors for severe Covid19, were randomized to a oral probiotic containing Lactiplantibacillus plantarum KABP022, KABP023, and KAPB033, with Pediococcus acidilactici strain KABP021, totaling 2 x 109 colony-forming units (n=150), or placebo (n=150), for 30 days. At endpoint, 293/300 subjects finished the study.

Primary clinical outcomes were:

• Complete remission was achieved by 78 of 147 (53.1%) in probiotic group compared to 41 of 146 (28.1%) in placebo (P< .001).
• Adverse events were lower in the probiotic group (p=0.008), though not statistically significant in those taking ≥2 medications daily (risk ratio 0.66 (95%CI 0.29-1.48)
• No hospitalizations or deaths occurred during the study.

Secondary clinical outcomes were:

• The probiotic treatment was well-tolerated and reduce the duration of both digestive and non-digestive symptoms, compared to placebo.
• The probiotic treatment was associated with reduce nasopharyngeal viral load compared to placebo (P < .001) and reduce lung infiltrates (P < .001).

Furthermore, the probiotic treatment

• significantly increased specific IgM and IgG against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and
• lower serum levels of high-sensitivity C-reactive protein (hsCRP) (P<00.1) and D-Dimer levels (P,00.1) compared to placebo.
• shortened median recovery time by 5 days (p<0.001).

• General practitioners, pharmacists, and clinic nurses are generally the first point of contact for patients who are not feeling well. Especially, during a pandemic when hospitals are inundated with patients who need urgent care. It is therefore essential for clinicians to have outpatient treatment protocols available to support the community.
• The microbiome is reported to be the first line of defense and interacts with the human host’s immune system. Therefore, probiotics may be useful as a preventative and supportive measure during a pandemic.
• Based on this study, practitioners could therefore consider a probiotic containing Lactiplantibacillus plantarum and Pediococcus acidilactici strains alone or in combination with other probiotic strains as a supportive measure.

• Future studies are needed to replicate these findings and elucidate its mechanism of action, particularly as fecal microbiome analysis in a subset of n=100 subjects did not detect a difference in fecal microbiome composition between groups at baseline or endpoint.
• Additionally, further studies are needed to identify specific probiotic strains that display immune effects and their required dosage.
• Elevated D-Dimer levels are associated with a higher risk of thrombotic events such as pulmonary embolism and have been associated with Covid19 severity and mortality. Therefore, further investigation of this probiotic formula in helping prevent thrombotic complications in Covid19 is warranted.
• All the subjects in the study were of Hispanic ethnicity, therefore further studies of other ethnicities are required.
• This study was capped at 60-year-olds, thus studies in older subjects are warranted.
• Conflict of interest statement: This study was fully funded by the manufacturer of the provided probiotic, and authors received either speaker fees or institutional support from the manufacturer.