Probiotics as a COVID-19 Prophylaxis
The role the gut microbiome has in modifying our innate immunity for better or worse infection outcomes is one of the least appreciated factors of epidemiology, likely because there isn’t much money to be made here. When salience is a function of corporate profitability modifiable risks like metabolic disease and vitamin D serum levels get ignored while patentable quick fixes get steered to the forefront of national discourse. That is why I will continue to highlight and summarize the scientific evidence for holistic alternatives and lower cost off label solutions to those being peddled by Big Pharma and their academic and regulatory stooges. Since 70-80% of the immune system is in the gut and SARS-Cov-2 has been associated with digestive system disturbances, reduced biodiversity of the gut microbiome and has been detected in fecal samples of infected people there is solid evidence that the virus infects the GI tract and thus interventions targeting the GI tract could reduce disease severity, reduce infections and possibly prevent COVID-19 disease entirely.
The first evidence that certain symbiotic gut bacteria could reduce the incidence and severity of upper respiratory tract infections emerged well before the pandemic. A 1998 rodent experiment was the first to find the immunological benefits of certain probiotics against respiratory infections, particularly the flu. Mice given a Bifidobacteria probiotic and immunized against influenza had enhanced serum IgG antibodies, mucosal IgA antibodies and better protection against flu infection compared to mice that were only immunized against the particular flu variant used in the study. A pilot study conducted in the early 2000s with elderly participants for 3 weeks during the winter found that participants given milk fermented with yoghurt cultures were sick for significantly fewer days and had significantly lower temperature fevers than participants given regular milk. A 4 week long double blind placebo controlled RCT conducted among professional rugby players found that players given probiotic supplementation had significantly fewer respiratory tract illnesses and sick days than placebo control players. There were no differences in illness severity between groups, likely because professional rugby players are already exceptionally healthy people with little room for improvement in their immune response to respiratory infections. A similar 4 month long double blind placebo controlled RCT conducted among long distance runners found that runners given a lactobacillus probiotic supplement for 30 days reported respiratory symptoms for fewer than half the days of the placebo group.
A double blind placebo controlled RCT conducted in Germany in the early 2000s over two three month winter/spring periods (n = 454) found that participants given a combination of a vitamin/mineral supplement plus a probiotic containing three different strains of bacteria, over 14 days, had a significantly shorter duration of common cold episodes and days with fever during a cold episode compared to the active placebo group who only received the vitamin and mineral supplement.
A double blind placebo controlled RCT conducted in Malaysia in 2018 among immunocompetent adults (n = 109) found participants who were given a lactobacillus supplement containing 10 billion colony forming units over 12 weeks had a significantly shorter duration of nasal symptoms by an average of 5 days fewer compared to placebo controls and suffered significantly less frequent upper respiratory tract infections in weeks 4 and 12 of the study. Administration of this probiotic also significantly increased interleukin-4 and interleukin-10 anti-inflammatory cytokine levels in young adults at week 12 and decreased inflammatory cytokines such as tumor necrosis factor and interferon gamma in all participants who were given the probiotic supplement over 12 weeks. Compared to placebo controls, two types of cytotoxic natural killer cells were also downregulated in young and middle aged adult participants in the treatment arm.
Naturally, prior evidence of probiotic effectiveness against several different types of viral and bacterial respiratory infections provoked curiosity about its possible effectiveness against COVID-19.
A matched case retrospective cohort study conducted at a hospital in China among COVID-19 patients between January 2020 and April 2020 (n = 375), found that patients given 3 daily doses of a 210 mg capsule containing three different bacteria strains had a shorter duration to clinical improvement in symptoms (median 18 days) compared to patients who received only the standard of care (median 21 days) and had a significantly shorter hospital stay (median 17 days) compared to the standard of care group (median 20 days).
A double blind placebo controlled RCT conducted in the U.S. among (unvaxxed) persons with exposure to at least one household contact diagnosed with with COVID-19 within the past seven days but not infected themselves or taking any antiviral or antibiotic treatments (n = 106), found, following intention to treat method, that participants given a 28 day regimen of Lacticaseibacillus rhamnosus GG consisting of 10 billion colony forming units per capsule were significantly less likely to report any COVID-19 symptoms by day 28 (26.4%) compared to placebo controls (43%) and had a significantly longer time to symptom onset even after controlling for between group differences in smoking and hypertension.
A quadruple blind placebo controlled RCT conducted at a general hospital in Mexico City among high risk COVID-19 adult outpatients no older than 60 years of age enrolled within 7 days of symptom onset (n = 293), found that outpatients given a daily probiotic capsule containing 4 different bacteria strains for 30 days were significantly more likely to have lower viral loads by day 15, experience complete remission of disease symptoms and test PCR negative at the final check up on day 30 (53.1%) compared to patients given the placebo (28.1%) and also reported significantly fewer days of fever, cough, headache, body aches, shortness of breath, nausea, diarrhea and abdominal pain compared to placebo controls. Patients given probiotic supplements also had higher anti-N IgG and IgM antibody levels on days 15 and 30, lower C reactive protein on day 15, and experienced overall symptom resolution a median of 5 days earlier than placebo controls indicating both a more robust immune response and lower disease severity.
A single center retrospective study conducted at a hospital in Istanbul, Turkey among COVID-19 patients hospitalized with moderate to severe disease between November 1, 2020 and December 15, 2020 (n = 44) found that patients administered a three day course of a probiotic containing 1 trillion colony forming units of a single bacterial strain per dose were hospitalized for a significantly shorter period of time (median of 7.6 days) compared to patients who did not receive any probiotics (median 13.6 days), had significantly lower levels of inflammatory interleukin 6 cytokines, and had a 4x lower COVID-19 mortality rate.
A randomized open label case control study conducted in a Spanish hospital in late 2020 and early 2021 among hospitalized adult COVID-19 patients who were allowed to receive several different antiviral drugs over the course of the study period (n = 41), found that patients who received a daily probiotic supplement capsule consisting of two different bacteria strains for a month significantly improved both digestive and non-digestive symptoms in a greater proportion of patients given probiotic capsules than patients assigned to the control group.
A double blind placebo controlled RCT conducted in Hong Kong among immunocompetent patients diagnosed with at least one symptom of Post-acute COVID-19 syndrome using U.S. CDC criteria between June 2021 and August 2022 (n = 463), found that patients given a bi-daily synbiotic preparation consisting of 10 billion colony forming units of three different bacteria strains and three different prebiotic compounds were significantly more likely to experience alleviation of post acute sequelae symptoms after 6 months of treatment compared to placebo controls including fatigue, memory loss, brain fog, gastrointestinal disturbance, and general unwellness.
This is in no way an exhaustive list of the evidence for the immunological benefits of probiotics only the 1) literature I had enough access to to discern the methodology and findings 2) those directly examining effectiveness against respiratory infections in general and COVID-19 in general.