Abstract: ORIGINAL RESEARCH published: 24 June 2021 doi: 10.3389/fbioe.2021.646184 Oropharyngeal Probiotic ENT-K12 Prevents Respiratory Tract Infections Among Frontline Medical Staff Fighting Against COVID-19: A Pilot Study Edited by: Stephen Allen Morse, Centers for Disease Control and Prevention (CDC), United States Reviewed by: Dorothee Von Laer, Innsbruck Medical University, Austria Sumit Ghosh, The Research Institute at Nationwide Children’s Hospital, United States *Correspondence: Qiang Wang wangqiang@wust.edu.cn Qingming Wu wuhe9224@sina.com Baoli Zhu zhubaoli@im.ac.cn Junbo Xia xjb47@126.com † These authors have contributed equally to this work and share first authorship Specialty section: This article was submitted to Biosafety and Biosecurity, a section of the journal Frontiers in Bioengineering and Biotechnology Received: 04 January 2021 Accepted: 11 May 2021 Published: 24 June 2021 Citation: Wang Q, Lin X, Xiang X, Liu W, Fang Y, Chen H, Tang F, Guo H, Chen D, Hu X, Wu Q, Zhu B and Xia J (2021) Oropharyngeal Probiotic ENT-K12 Prevents Respiratory Tract Infections Among Frontline Medical Staff Fighting Against COVID-19: A Pilot Study. Front. Bioeng. Biotechnol. 9:646184. doi: 10.3389/fbioe.2021.646184 Qiang Wang 1* † , Xuan Lin 2† , Xiaochen Xiang 1 , Wanxin Liu 1 , Ying Fang 2 , Haiping Chen 2 , Fang Tang 2 , Hongyan Guo 2 , Di Chen 2 , Xiafen Hu 1 , Qingming Wu 1* , Baoli Zhu 3,4,5,6* and Junbo Xia 7* 1 Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Medical College, Wuhan University of Science and Technology, Wuhan, China, 2 Huarun WISCO General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, China, 3 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China, 4 Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China, 5 Beijing Key Laboratory of Antimicrobial Resistance and Pathogen Genomics, Beijing, China, 6 Department of Pathogenic Biology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, China, 7 Department of Pulmonary Medicine, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China Healthcare workers at the frontline are facing a substantial risk of respiratory tract infection during the COVID-19 outbreak due to an extremely stressful work schedule and public health event. A well-established first-line defense on oropharyngeal microbiome could be a promising strategy to protect individuals from respiratory tract infections including COVID-19. The most thoroughly studied oropharyngeal probiotic product which creates a stable upper respiratory tract microbiota capable of preventing upper respiratory tract infections was chosen to evaluate the safety and efficacy on reducing episodes of upper respiratory tract infections for COVID-19 healthcare workers. To our knowledge to date, this is the very first study describing the beneficial effects of oropharyngeal probiotic been administered by healthcare workers during the COVID-19 pandemic. In this randomized controlled trial, we provided the probiotics to frontline medical staff who work in the hospitals in Wuhan and had been in close contact with hospitalized COVID-19 patients for prophylactic use on a daily basis. Our finding suggests that oropharyngeal probiotic administration significantly..