Abstract: nutrients Article Ongoing Treatment with a Spore-Based Probiotic Containing Five Strains of Bacillus Improves Outcomes of Mild COVID-19 Adrian Catinean 1 , Anamaria Sida 1, *, Celina Silvestru 1 and Gheorghe G. Balan 2 1 2 * Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania Correspondence: ana.sida04@gmail.com Abstract: Spore-based Bacillus probiotic treatment improves intestinal health. The intestinal microbiota influences both the innate and adaptive immune responses. As such, the influence of ongoing spore-based probiotic treatment (five probiotic strains of Bacillus) on the clinical outcomes of mild COVID-19 was evaluated in this retrospective, observational study. Demographics, medical history, probiotic use, and COVID-19 symptom information were collected. The study included 120 patients with a PCR-confirmed SARS-CoV-2 infection and mild COVID-19 symptoms. The probiotic group (n = 60) comprised patients with ongoing probiotic treatment (≥1 month); the control group comprised patients not taking probiotics (n = 60). The primary outcome was time to symptom resolution; secondary outcomes included time to fever resolution and presence of digestive symptoms. The probiotic group had a significantly shorter time to symptom resolution (mean (95% confidence interval) days: control group, 8.48 (6.56, 10.05); probiotic group, 6.63 (5.56; 6.63); p = 0.003) and resolution of fever (control group, 2.67 (1.58, 3.61); probiotic group, 1.48 (1.21, 2.03); p < 0.001). More patients in the probiotic group (n = 53) than in the control group (n = 34) did not have digestive symptoms (p < 0.001). Among adults with mild COVID-19, participants receiving ongoing probiotic treatment had a shorter clinical course, and fewer had digestive symptoms compared with those not taking probiotics. Citation: Catinean, A.; Sida, A.; Keywords: Bacillus; COVID-19; probiotics; SARS-CoV-2; time to symptom resolution; gut microbiota; gut–lung axis; gastrointestinal COVID-19 symptoms; immunomodulation; fever in COVID-19 infection Silvestru, C.; Balan, G.G. Ongoing Treatment with a Spore-Based Probiotic Containing Five Strains of Bacillus Improves Outcomes of Mild COVID-19. Nutrients 2023, 15, 488. https://doi.org/10.3390/ nu15030488 Academic Editor: Gang Wang Received: 16 December 2022 Revised: 5 January 2023 Accepted: 12 January 2023 Published: 17 January 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).