Application of LiveSpo Navax in Treatment of Acute Respiratory Disease in Children Infected With Respiratory Syncytial Virus

Respiratory syncytial virus (RSV) is the most common virus that causes Acute Respiratory Tract Infections (ARTIs) in young children, with a high risk of serious bronchiolitis. RSV infection symptoms range from mild fever, cough, runny nose, and wheezing to severe symptoms such as difficulty breathing and respiratory failure. Cytokines in the airways of children with bronchiolitis, such as tumor necrosis factor (TNF-alpha), Interleukin-6 (IL-6) and IL-8, have been shown to increase at a very high level in primary RSV infection, and extreme elevation of IL-6 is associated with sudden death in children with RSV infection. The World Health Organization (WHO) estimates that 160,000-600,000 children under the age of five die or hospitalize each year as a result of RSV infection. There is currently no vaccine or specific treatment for RSV-infected children because monoclonal antibody palivizumab therapy and antiviral nucleotide drug ribavirin are either too expensive or too dangerous for children and are only recommended for high-risk patients.

In recent years, preventive and supportive therapies for respiratory tract infection have grown in popularity, with probiotics emerging as promising safe candidates for therapeutic support and antibiotic reduction. It is suggested that probiotics can capture viruses through direct interactions, or produce secondary growths that inhibit virus growth or stimulate the immune system to capture virus intrusion. However, the efficacy of oral digested probiotics on children's respiratory tracts has been slow to develop (normally it takes about 3-12 months) and is primarily used for prevention rather than supportive treatment of ARITs. As a result, alternative delivery routes for probiotics in the treatment of ARTIs are required.

The aim of the study about to evaluate the effectiveness of nasal-spraying probiotics containing two bacterial strains, Bacillus subtilis and Bacillus clausii in preventing and in supporting the treatment of children having acute respiratory symptoms due to RSV infection.

Methods: A randomized, blind, and controlled clinical trial are conducted. The patient's parents are required to provide the following information of their children: full name, sex, age, obstetric history, vaccination history, antibiotic use history... After informed consent, 100 patients with ARTIs due to RSV will be randomized into 2 groups (n = 50/group): the control group (named "Control" group) use 0.9% NaCl physiological saline and an experimental group (named the "Navax" group) use the probiotics LiveSpo Navax. The patient is given a coded spray in the form of a blind sample to ensure the objectivity of the study. The clinical follow-up will be 6 days, nasopharyngeal samples will be collected at day 0 and day 3 to evaluate potential reductions in viral load and co-infection bacteria, as well as modulation of overreacted cytokine release and the presence of probiotic spores in the patient's nasal mucosa.

Real-time PCR for detection of microorganism in nasopharyngeal samples: semi-quantitative assays for measuring changes in RSV load and co-infection bacterial concentrations is conducted by the real-time RT-PCR/PCR routine protocol which has been standardized under ISO 15189:2012 criteria and used in Vietnam National Children's Hospital. Detection of B. subtilis ANA4 and B. clausii ANA39 are also conducted by real-time PCR SYBR Green that has been standardized under ISO 17025: 2017 standard and routinely in the Key Laboratory of Enzyme and Protein Technology, VNU University of Science.