Clinical Effects of Streptococcus salivarius K12 in Hospitalized COVID-19 Patients: Results of a Preliminary Study
RCT 50 hospitalized patients in Pakistan, 25 treated with S. salivarius K12, showing lower mortality with treatment, without statistical significance. There were more patients with higher oxygen requirements at baseline in the control group - 18 vs. 6 with O2 ≥ 8 L/min.
The immune effects of probiotics are strain-specific.
This study is excluded in the after exclusion results of meta
unadjusted differences between groups.
risk of death, 62.5% lower, RR 0.38, p = 0.17, treatment 3 of 25 (12.0%), control 8 of 25 (32.0%), NNT 5.0.
risk of ICU admission, no change, RR 1.00, p = 1.00, treatment 8 of 25 (32.0%), control 8 of 25 (32.0%).
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Di Pierro et al., 28 Sep 2022, Randomized Controlled Trial, Pakistan, peer-reviewed, mean age 48.5, 7 authors, study period 11 August, 2021 - 18 November, 2021, trial NCT05043376 (history)
email@example.com (corresponding author).
Clinical Effects of Streptococcus salivarius K12 in Hospitalized
COVID-19 Patients: Results of a Preliminary Study
Francesco Di Pierro 1,2, * , Somia Iqtadar 3 , Sami Ullah Mumtaz 3 , Alexander Bertuccioli 4 , Martino Recchia 5 ,
Nicola Zerbinati 6 and Amjad Khan 7
Scientific & Research Department, Velleja Research, 20100 Milan, Italy
Digestive Endoscopy, Fondazione Poliambulanza, 25133 Brescia, Italy
Department of Medicine, King Edward Medical University, Lahore 54000, Pakistan
Department of Biomolecular Sciences (DISB), University of Urbino, 61029 Urbino, Italy
Medistat, Unità di Epidemiologia Clinica e Biostatistica, 20100 Milan, Italy
Department of Medicine and Surgery, University of Insubria, 21100 Varese, Italy
Nuffield Division of Clinical and Laboratory Sciences (NDCLS), Radcliffe Department of Medicine,
John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK
Correspondence: firstname.lastname@example.org; Tel.: +39-0523-510848; Fax: +39-0523-511894
Academic Editor: Despoina Koulenti
Abstract: Anatomical and physiological considerations indicate that the oral cavity is a primary
source of the lung microbiota community, and recent studies have shown that the microbiota in
the lungs contributes to immunological homeostasis, potentially altering the organ’s susceptibility
to viral infection, including SARS-CoV-2. It has been proposed that, in the case of viral infection,
lung Gram-negative bacteria could promote the cytokine cascade with a better performance than
a microbiota mainly constituted by Gram-positive bacteria. Recent observations also suggest that
Prevotella-rich oral microbiotas would dominate the oral cavity of SARS-CoV-2-infected patients. In
comparison, Streptococcus-rich microbiotas would dominate the oral cavity of healthy people. To
verify if the modulation of the oral microbiota could have an impact on the current coronavirus
disease, we administered for 14 days a well-recognized and oral-colonizing probiotic (S. salivarius
K12) to hospitalized COVID-19 patients. The preliminary results of our randomized and controlled
trial seem to prove the potential role of this oral strain in improving the course of the main markers
of pathology, as well as its ability to apparently reduce the death rate from COVID-19. Although
in a preliminary and only circumstantial way, our results seem to confirm the hypothesis of a
direct involvement of the oral microbiota in the construction of a lung microbiota whose taxonomic
structure could modulate the inflammatory processes generated at the pulmonary and systemic level
by a viral infection.
Received: 27 August 2022
Keywords: oral microbiota; lantibiotics; salivaricins; Streptococcus salivarius; COVID-19; SARS-CoV-2
Citation: Di Pierro, F.; Iqtadar, S.;
Mumtaz, S.U.; Bertuccioli, A.;
Recchia, M.; Zerbinati, N.; Khan, A.
Clinical Effects of Streptococcus
salivarius K12 in Hospitalized
COVID-19 Patients: Results of a
Preliminary Study. Microorganisms
2022, 10, 1926. https://doi.org/
Accepted: 24 September 2022
Published: 28 September 2022
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