Abstract: Medicine ® Clinical Trial/Experimental Study The short-term effect of different chlorhexidine forms versus povidone iodine mouth rinse in minimizing the oral SARS-CoV-2 viral load An open label randomized controlled clinical trial study Zuhair S. Natto, DrPHa,* , Muhammed A. Bakhrebah, PhDb, Marwah Afeef, MScc, Samiah Al-Harbi, BAd, Majed S. Nassar, PhDb, Abdulkarim F. Alhetheel, PhDe,f, Heba Ashi, PhDa Abstract Several investigations evaluated the possibility of different types of mouth wash rinse in minimizing the SARS-CoV-2 load. However, results still controversial. The study aim is to assess the short-term efficiency of several over-the-counter mouth rinses and lozenges in minimizing the salivary viral load for SARS-CoV-2 in patients with confirmed COVID-19 in comparison to saline. This is a randomized controlled clinical trial with 4 arms. The recruited cases were randomized using a simple randomization technique and were assigned to chlorhexidine digluconate mouth rinse (CHX mouth rinse), 2 mg of chlorhexidine digluconate lozenges (CHX lozenges), povidone iodine mouth rinse (PVP-I mouth rinse) or saline as a control group. Saliva were collected from all study subjects by passive drool technique at two time points. First, prior to intervention with mouth rinse or the lozenges, the baseline saliva sample was collected. Second saliva samples were collected immediately after the mouth rinse. Real time PCR was conducted and the value threshold cycle (Ct) for each sample was recorded. Majority of the participants had an education level of high school or less (60%), were married (68.3), males (58.3%), and nonsmokers (58.5%). No statistically significant differences between groups at the two times test (P > .05). However, a significant decrease of salivary viral load in all four groups combined (P-value for E genes = .027, and for S genes = .006), and in PVP-I mouth rinse specifically (P = .003 and P = .045, respectively). Povidone iodine mouth rinse showed a potential influence on the reduction of the viral load on a short-term basis. However, longer-term studies of the effect of these products should be conducted. Abbreviations: CHX mouth rinse = digluconate mouth rinse, CHX lozenges = chlorhexidine digluconate lozenges, PVP-I mouth rinse = povidone iodine mouth rinse, Ct = threshold cycle, SARS-CoV-2 = Severe Acute Respiratory Syndrome Coronavirus 2, KFGH = King Fahad General Hospital, RT-PCR = Real-time polymerase chain reaction. Keywords: COVID-19, SARS-CoV-2, mouth rinse, chlorhexidine digluconate, povidone iodine especially given the new variants, and the chances of its transmission with asymptomatic patients is still very high.[7] The SARS-CoV-2 incubation period has been reported to range between 1 and 14 days, with most evidence suggested it to be 3 to 7 days.[5] Therefore, there is evidence indicating the possibility of infection spreading when patients were unaware about their infection status and asymptomatic.[8,9] Current evidence proved saliva can act as a SARS-CoV-2 reservoir.[9] Several reports found that the virus is transmitted through aerosols, which pose a significant possibility for transmission risk of the infection in dental clinics.[5,7] So, it is required to decrease this potential risk in dental offices, by minimizing the salivary SARS-CoV-2 load, if possible,