The main finding of this study was that the cumulative incidence of COVID-19 in the test community was lower than that in the control community during the use of a population-based virucidal phthalocyanine gargle/rinse protocol. This is a promising result, as COVID-19 is very recent, and there is still no "gold standard" treatment; thus, actions based on primary prevention measures to slow down and interrupt transmission are essential. Populations pre-experienced in viral epidemics adopted preventive measures with good risks and benefits, which is defended, such as social distancing, washing hands, wearing masks, and gargling/rinsing with antiseptic solutions.18–21 Since saliva was an important source of virus transmission during the pandemic, protective measures, such as the use of antiseptic gargles were adopted and recommended by several countries and organizations against SARS-CoV-2.5, 10, 21–23
Some studies have shown that the use of a mouthwash containing APD can reduce the viral load of SARS-CoV-2, acting as a therapeutic aid in reducing the severity and risk of COVID-19 transmission. 8–9, 22–24 These data corroborate the findings of the present study. The municipalities divided as test and control did not differ in terms of disease risk before the period of distribution of mouthwashes (phase 1) (p>0.05); however, disease risk was lower in the test than in the control community after the widespread use of the mouthwash/gargling protocol with APD.
COVID-19 is a disease with pandemic characteristics that spreads according to population mobility.16 The municipalities selected in this community trial had similar population sizes and social indicators. They belonged to the same geographic mesioregion, had a similar structure to primary healthcare, and were connected by a single route with neighboring municipalities.25–26 In both communities, the measures to control the COVID-19 pandemic in the whole study period were similar regarding the recommendations for social distance and self-administered hygiene measures inducing people to wear face masks, frequently wash their hands with soaps, and, if necessary, use alcohol gel on the hands. Therefore, there were no reasons for any incidence difference in COVID-19 cases from both communities, except for the virucidal phthalocyanine gargle/rinse protocol used in the test community. Owing to these points, the comparison presented herein is assumed to be licit.
The cumulative incidence difference of COVID-19 at the population level in the test community was nearly significant, showing promising findings. Prior to the beginning of the use of the APD mouthwash the cumulative COVID-19 cases were visually similar; however, at the 38th week, the test community’s curve seemed to deflect differently with a small number of new cases, while still showing a slight increase. However, despite the control community continuing to increase the COVID-19 cases, in the test community, new cumulative cases per 1,000 inhabitants were lower than those in the control community. In phase 2, the moment the population was exposure to the APD mouthwash, the relative risk decreased to 0.46, suggesting a preventive effect in the test community. The p-value was borderline (p=0.076) to significant, sufficient to be considerable in an epidemiologic study in a very difficult history moment. After phase 2, both communities increased the number of new COVID-19 cases. After the intervention period, the test community data returned to the new cumulative case curve similar to the control community, reinforcing the potential effect of the APD mouthwash at the population level.
Saliva is a source of biological fluid in the spread of the disease COVID-19. The presence of SARS-CoV-2 in saliva causes viral proliferation and consequent RNA secretion in any cells involved in the production of salivary components, such as salivary glands, respiratory tract cells, and the periodontal tissue.27–28 Although our research did not analyze the salivary components and substantivity, we observed a difference in COVID-19 risk in the test community compared to the control community. This was supported by the finding that the virus has been consistently detected in saliva; thus, the oral cavity was a source of SARS-CoV-2.29 Thus, rinsing/gargling with an APD solution could reduce the chemical/mechanical action of the virus from the oral cavity and throat. In addition, a chemical antiviral aerosol can be generated and inhaled to protect the upper airways when a gargle is done.
Strengths and limitations of this study must be considered in relation to the methodology used. The study was undertaken in an adverse historic moment, and the field team did not have the conditions to register the use of the APD mouthwash. Thus, important variables, such as the personal/family’s behavior related to COVID-19 could not be obtained to control for possible confounding factors. On the opposite, all the assessments were conducted at the population level, without any interference from the research group regarding each case and were publicly registered in both communities. It is noteworthy that the results were observed in the Brazilian context in which the testing strategy was restricted. The widespread use of masks, which could have also contributed to reducing the transmissibility of COVID-19, was not assessed in this study. A difference in COVID-19 cumulative cases was observed in the current study, suggesting an effect of the intervention and possible contribution to prevent the health system from collapsing while preserving lives.