Global Journal of Medical Research, F: Diseases, Volume 23 Issue 2

experiment in a closed space in which 0.01 ppmv CD gas inactivated more than 99% of all floating viruses (Ogata et al., 2016). More than 99% of the viruses adhering to the surface of objects were also inactivated by 0.007 ppmv CD gas (Morino et al., 2013).In vivo experiments suggested that 0.03 ppmv CD gas prevented influenza infection in mice (Ogata & Shibata, 2008). In vitro experiments using a CD gas-releasing agent have also shown inactivation of the avian influenza virus A (H7N9) (Sun et al., 2022). Further, studies in humans have suggested that the use of CD gas-releasing agents is effective against viral infections (Mimura et al., 2010; Ogata & Shibata, 2009). Although CD gas-releasing agents can be expected to be useful for COVID-19 prophylaxis, no studies have been conducted to investigate the relationship between COVID-19 infection and CD gas- releasing agents. Therefore, the purpose of this study was to conduct a retrospective study of the relationship between the use of CD gas-releasing agents and the incidence of COVID-19 in elementary schools. II. M aterial and M ethods a) Design This multicenter, retrospective study investigated the relationship between the incidence of COVID-19 and the use of CD gas-releasing, from January to March 2022, using a database created by the City Board of Education. This study was approved by the Juntendo University School of Medicine Medical Research Ethics Committee (Research Project No. E22- 0382). b) Subjects The subjects of this study were first- to sixth- grade (approximately 6 to 12 years old) male and female students in public elementary schools under the jurisdiction of a municipal board of education in an urban area in Japan. Since there was no precedent for this study, the sample size could not be calculated. No exclusion criteria were established as this was an exploratory study. c) CD gas-releasing agent CD gas-releasing agents (Cleverin® pro Gel Large type for 50m2(Taiko Pharmaceutical Co.) and Cleverin Pro Pouch type for 30 m2, Taiko Pharmaceutical Co., Ltd., Japan) are made by adding sodium dihydrogen phosphate to sodium chlorite and solidifying the mixture by adding superabsorbent polymers, which then generate and release CD gas continuously for several months. Those agents, which can be safely used in an inhabited environment, were provided free of charge by Taiko Pharmaceutical Co., Ltd. to city school boards for marketing purposes. They were further distributed by city school boards to elementary schools that requested them from January 2022 through March 2022. It was recommended that those agents be provided in classrooms at a rate of one unit per 30 m2 or 50 m2 in the case of Cleverin Pro Pouch type or Placeable type, respectively. d) Incidence of COVID-19 The number of infections of COVID-19 was investigated in all elementary schools from January to March 2022. The parents of the children were requested to notify the schools when the PCR test for COVID-19 was positive, when the antigen test was positive, or when a physician determined that COVID-19 was strongly suspected. These reports were compiled by the elementary schools and reported to the city's board of education. The city school board created a database of the CD gas-releasing agents provided and the number of COVID-19 infections. e) Statistical analysis The distribution by a number of elementary school students was shown as the median (25th–75th percentile values), since the Kolmogorov-Smirnov normality test did not allow for a normal distribution. The association between the use of CD gas-releasing agents and the incidence of COVID-19 was analyzed using crude odds ratios of the subjects who suffered from COVID-19. Incidence as cases were defined as the number of reported COVID-19 incidences, and controls (non-incidence) were defined as the number of children minus the number of reported COVID-19 infections. The significance level was p<0.05, and IBM SPSS Statistics® ver. 28 was used for statistical analysis. III. R esults A summary of the elementary schools analyzed in this study is shown in Table 1. Sixty-eight elementary schools (n = 34,810) did not use any CD gas-releasing agent, whereas 96 (n = 38,714) used those agents. Table 2 shows the odds ratio for incident COVID-19. Elementary schools that did not use chlorine dioxide-releasing agents had higher odds (odds ratio: 0.934, 95% confidence interval: 0.895–0.975) of COVID- 19 incidence than those that did. IV. D iscussion This exploratory study investigated the relationship between the use of CD gas-releasing agents in classrooms and COVID-19 infections in elementary schools and showed that elementary schools that used those agents had significantly lower odds ratios for COVID-19 incidence than those that did not. A previous study showed that in an intervention study of Ground Self-Defense Forces personnel, a group that used those CD gas-releasing agents in a room had significantly lower numbers of cases of influenza-like illnesses than the non-intervention group 2 Year 2023 Global Journal of Medical Research Volume XXIII Issue II Version I ( D ) F © 2023 Global Journals Relationship between COVID-19 and use of Chlorine Dioxide Gas-Releasing Agents in Elementary Schools