Randomized, Double-Blind, Placebo-Controlled Trial of a Throat Spray with Selected Lactobacilli in COVID-19 Outpatients
De Boeck, Ilke; Cauwenberghs, Eline; Spacova, Irina; Gehrmann, Thies; Eilers, Tom; Delanghe, Lize; Wittouck, Stijn; Bron, Peter A; Henkens, Tim; Gamgami, Imane; Simons, Alix; Claes, Ingmar; Mariën, Joachim; Ariën, Kevin K; Bakokimi, Diana; Loens, Katherine; Jacobs, Kevin; Ieven, Margareta; Bruijning-Verhagen, Patricia; Delputte, Peter; Coenen, Samuel; Verhoeven, Veronique; Lebeer, Sarah
(2022) Microbiology spectrum, volume 10, issue 5
(Article)
Abstract
Primary care urgently needs treatments for coronavirus disease 2019 (COVID-19) patients because current options are limited, while these patients who do not require hospitalization encompass more than 90% of the people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we evaluated a throat spray containing three Lactobacillaceae strains
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with broad antiviral properties in a randomized, double-blind, placebo-controlled trial. Before the availability of vaccines, 78 eligible COVID-19 patients were randomized to verum (n = 41) and placebo (n = 37) within 96 h of a positive PCR-based SARS-CoV-2 diagnosis, and a per-protocol analysis was performed. Symptoms and severity were reported daily via an online diary. Combined nose-throat swabs and dried blood spots were collected at regular time points in the study for microbiome, viral load, and antibody analyses. The daily reported symptoms were highly variable, with no added benefit for symptom resolution in the verum group. However, based on 16S V4 amplicon sequencing, the acute symptom score (fever, diarrhea, chills, and muscle pain) was significantly negatively associated with the relative abundance of amplicon sequence variants (ASVs) that included the applied lactobacilli (P, 0.05). Furthermore, specific monitoring of these applied lactobacilli strains showed that they were detectable via quantitative PCR (qPCR) analysis in 82% of the patients in the verum group. At the end of the trial, a trend toward lower test positivity for SARS-CoV-2 was observed for the verum group (2/30; 6.7% positive) than for the placebo group (7/27; 26% positive) (P = 0.07). These data indicate that the throat spray with selected antiviral lactobacilli could have the potential to reduce nasopharyngeal viral loads and acute symptoms but should be applied earlier in the viral infection process and substantiated in larger trials.
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Keywords: Antiviral Agents/therapeutic use, COVID-19, COVID-19 Testing, COVID-19/drug therapy, Humans, Lactobacillus, Outpatients, Pandemics/prevention & control, Pharynx, SARS-CoV-2, Treatment Outcome, lactobacilli, microbiome, throat spray, Journal Article, Randomized Controlled Trial
ISSN: 2165-0497
Publisher: American Society for Microbiology
Note: Funding Information: I.D.B. and I.S. were supported by grants from the Research Foundation—Flanders (FWO) (postdoctoral grants 12S4222N and 1277222N), and I.D.B. was also supported by a small research grant from the University of Antwerp (BOF KP 43829). E.C. is supported by iBOF grant POSSIBL. T.H., A.S., and I.C. were supported by a research grant from Flanders Innovation and Entrepreneurship (HBC.2020.2923). K.K.A. was supported by the Research Foundation—Flanders (G0G4220N) and by an intramural grant (a subsidy from the Department of Economy, Science, and Innovation [EWI] from the Flemish Government). L.D. was supported by a Baekeland mandate from Flanders Innovation and Entrepreneurship (HBC.2020.2873). S.L., T.H., and T.E. were supported by a European Research Council grant (Lacto-Be 26850). The application of the real-time duplex PCR for the detection of SARS-CoV-2 and RNase P was funded through the RECOVER project (European Commission under H2020 call SC1-PHE-CORONAVIRUS-2020). Funding Information: I.D.B., I.S., I.C., T.H., and S.L. are inventors on a patent application (BE2021/5643) related to this work. I.C., T.H., I.G., and A.S. are working at Yun NV (www.yun.be), which formulated the spray for this study. S.L. is a member of the scientific advisory board of Yun NV. The Ph.D. research of L.D. is currently funded by the VLAIO through a Baekeland mandate in collaboration with Yun NV. Yun NV was not involved in the clinical study design or data analysis of this work. P.A.B. is a consultant for multiple companies in the food and health industries, but they were not involved in the manuscript. The remaining authors have no conflicts of interest to declare related to this work. Publisher Copyright: © 2022 De Boeck et al.
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