Povidone-iodine (PVP-I) is a time-tested antiseptic agent with excellent virucidal (99.99%) properties. Repurposing it against coronavirus disease-19 (COVID-19) is a relatively newer concept and has been sparsely tested in vivo. The most common route of entry of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) is the nasopharynx. Hence, it was targeted to prevent access and contamination of the nasopharynx by several protective measures, including facemasks. Averting colonization of the virus could be one of the best options to reduce the incidence of infection. PVP-I gargle and mouthwash were found to be effective in vitro rapid inactivation against SARS-CoV-2 on a smaller scale [1, 2]. However, efficacy in humans is lacking. To assess the virucidal effect of PVP-I against SARS-CoV-2 located in the nasopharynx was the objective of this parallel armed randomized clinical trial.


This single-center, open-label randomized clinical trial with a 7-arm parallel-group design was approved by the ethical review committee of Dhaka Medical College, Bangladesh. (NCT Identifier number: NCT04549376). We screened all reverse transcription-polymerase chain reaction (RT-PCR)-confirmed COVID-19 cases aged 18 years and above with symptoms. Written informed consent was obtained before randomization. Nasopharyngeal clearance of SARS-CoV-2 was tested after single time application of PVP-I nasal irrigation (NI) at diluted concentrations of 0.4%, 0.5% and 0.6% and PVP-I nasal spray (NS) at diluted concentrations of 0.5% and 0.6%. All groups were compared to the corresponding controls (distilled water). The primary outcome was viral clearance in a repeat RT-PCR (qualitative), and the secondary outcome was the number of adverse events. Final data analysis was performed using the statistical software SPSS (Version 20). The authors followed the Extension of the Consolidated Standards of Reporting Trials (CONSORT) 2010 guideline [3]. The study protocol was published elsewhere [4].


A total of 189 confirmed COVID-19 cases were randomized into seven groups: 27 patients in each group. All of them completed the study. Of all, 159 (84.1%) were male, and 30 (15.9%) were female. The average age of the participants was 43.98 ± 12.67 years (SD), with the majority ranging from 31 to 40 years (n = 56, 29.60%). The PVP-I NS group had significantly higher proportions of severe patients than the control-NS (C-NS) group (p < 0.001). The 0.6% NS group differed from the C-NS group by sex and the presence of comorbidities (p < 0.05). Adjusting the differences, we observed a statistically significant proportion of nasopharyngeal clearance with all strengths of PVP-I NI and PVP-I NS compared to the corresponding controls. Additionally, 0.5% NI was significantly better than 0.5% NS for viral clearance (p = 0.018) and had the highest nasopharyngeal clearance among all strengths (n = 25, 92.6%) and 0.6% NS is best among 0.5% NS and CNS. The only adverse event was nasal irritation recorded in two patients each in the 0.4% and 0.6% PVP-I NI groups (Tables 1 and 2).

Table 1 Patient Demographics, baseline clinical characteristics and virucidal activity of PVI-P Nasal spray and mouth wash
Table 2 Level of significance table for pair-wise comparisons of patient demographics, baseline clinical characteristics and virucidal activity of PVI-P Nasal spray and mouth wash


Although in vitro testing of PVP-I solution revealed a considerable reduction in SARS-CoV-2 viral titers, its effect on humans was unclear [1]. Our study confirms the presumed effectiveness of PVP-I in nasopharyngeal clearance of SARS-CoV-2 among COVID-19 patients. Compared to controls, we noted viral clearance at two-fifth to three-fifth dilutions of PVP-I nasal irrigation and spray. Our findings agree with the first report of in vivo PVP-I mouthwash application [5]. In contrast, Guenezan et al. [6] observed no effect of PVP-I on nasopharyngeal viral loads. They reported unpleasant nasal tingling and transient elevation of thyroid stimulating hormone after povidone iodine administration. In contrast, we found nasal irritation in only two patients (1.1%). Our study’s strength was testing different strengths of PVP-I nasal solution and comparing those with distilled water controls in a modest number of cases. However, our limitation was the inability to conduct viral quantification before and after intervention.


In this study, a statistically significant proportion of nasopharyngeal clearance with all strengths of PVP-I NI and PVP-I NS (compared to the corresponding controls) is observed, so our recommendation is to use PVP-I prophylactically in nasopharynx as well as oropharynx (through which areas SARS-CoV-2 enters and resides for a while) for prevention of COVID-19.