Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a .... trial, 2022, Gutiérrez-Castrellón et al

Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial
2022 study

ABSTRACT

Intestinal bacteria may influence lung homeostasis via the gut-lung axis. We conducted a single-center, quadruple-blinded, randomized trial in adult symptomatic Coronavirus Disease 2019 (Covid19) outpatients. Subjects were allocated 1:1 to probiotic formula (strains Lactiplantibacillus plantarum KABP022, KABP023, and KAPB033, plus strain Pediococcus acidilactici KABP021, totaling 2 × 109 colony-forming units (CFU)) or placebo, for 30 days.

Co-primary endpoints included: i) proportion of patients in complete symptomatic and viral remission; ii) proportion progressing to moderate or severe disease with hospitalization, or death; and iii) days on Intensive Care Unit (ICU).
Three hundred subjects were randomized (median age 37.0 years [range 18 to 60], 161 [53.7%] women, 126 [42.0%] having known metabolic risk factors), and 293 completed the study (97.7%).
Complete remission (i.e. complete symptomatic and viral clearance*) on day 30 was achieved by 78 of 147 (53.1%) in probiotic group compared to 41 of 146 (28.1%) in placebo (RR: 1.89 [95 CI 1.40–2.55]; P < .001), significant after multiplicity correction. No hospitalizations or deaths occurred during the study, precluding the assessment of remaining co-primary outcomes.
Probiotic supplementation was well-tolerated and reduced nasopharyngeal viral load, lung infiltrates and duration of both digestive and non-digestive symptoms, compared to placebo.
No significant compositional changes were detected in fecal microbiota between probiotic and placebo, but probiotic supplementation significantly increased specific IgM and IgG against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) compared to placebo.

It is thus hypothesized this probiotic primarily acts by interacting with the host’s immune system rather than changing colonic microbiota composition. Future studies should replicate these findings and elucidate its mechanism of action (Registration: NCT04517422).

*Requires negative RT-qPCR (viral clearance) plus complete resolution of all five Covid19 symptoms considered at study entry (symptomatic clearance).

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This is an interesting inclusion!

 

The product page:
https://www.ab21probiotic.com/

 

What I don’t understand, is that it looks like the probiotic group broadly had a stronger immune response, but also had less symptoms?

Wouldn’t a stronger immune response lead to more severe symptoms? Isn’t SARS (severe acute respiratory syndrome) mostly the immune system reacting so strongly it damages the lungs.

 

I'd guess the most likely reason would be that "immune response" is a very broad term. ARDS is caused by a cytokine storm (highly elevated levels of pro-inflammatory cytokines) from what I remember - this is an overactivation in that case. Here, it seems like the antibody response against SARS CoV 2 is increased, which could lead to quicker neutralization of the virus? That how I would interpret it anyways?

 

I don’t understand the 15 day data point for blue (probiotics). And what happened to the error bars?

Edit: it’s figure 2.

 

Good question, looks like they might have deleted outliers that would have messed with statistical significance? Any other reasons?

 

I believe the only way to get a bar like the fourth one would be if all values = 2. But that would give you an error bar = 0. The current one goes from 1-4.

 

So, the box are the quartiles, right? Meaning in that bar it looks like all the patients in the mid 50% of the Gauss curve had a score of 2. Then there's outliers making the error bars which are the 95% CI of the mean?

 

Good point.
The paper says:

Box plot example from google: