The proposed study is a prospective randomized double blinded placebo-controlled study of
6-weeks in duration. Patients who have tested positive and diagnosed with COVID-19 within the
previous 72 h and who meet the inclusion and exclusion criteria, will be invited to
participate in this study.

This study will be involving non-hospitalized patients who are recovering at home. One arm
will use betadine sinonasal rinses and a betadine mouth gargle while another arm will act as
a control receiving a placebo (a food coloring agent). A third arm will use a 0.6% PVP-I gel
forming nasal spray twice daily. A baseline saliva sample will be collected to assure a
positive COVID-19 test and to quantify viral load. Repeat saliva samples will be collected
every 2 days for 2 weeks, then at 4 weeks and 6 weeks to quantify test status and quantify
viral load reduction. WURSS-44 questionnaires will be completed daily for 2 weeks and then
again at 4 weeks and 6 weeks. SNOT-22 questionnaires will be completed at baseline and then
again at 2 weeks, 4 weeks, and 6 weeks. The investigators will also monitor for worsening of
symptoms and the need for hospitalization for the entire 6 week duration of the study.

Upon enrolment in the study after obtaining positive results for COVID-19, demographic data
and clinical data will be obtained by the investigators. Patients will be randomly assigned
to one of the study arms delineated above by permuted block randomization

The clinical samples that detect COVID-19 are obtained by collecting a saliva sample prior to
rinsing. This will avoid confounding by artificially lowering the viral particles sampled and
will minimize any potentially inhibitory effects of the intervention compounds on lab
detection. The sample will be put into a sterile collection container and stored in the
fridge until it is transported to the laboratory for analysis.

Sample Size

Considering the quick turnover and the rapid doubling time in the number of positive cases
and the unprecedented nature of this study's design and treatment, the investigators hope to
recruit 20 patients in each study arm as a pilot study around this subject matter. To account
for a drop-out rate of 25% the investigators plan to recruit 27 patients in each arm.

Analysis

Primary outcomes

1. Time to a negative/undetectable RT-PCR SARS-CoV-2 saliva sample amongst patients rinsing
and gargling with 0.23% PVP-I compared to a placebo group measured during the study
treatment daily for 2 weeks and at the 4-week and 6-week mark.

1.1. A Kaplan-Meier curve and log rank test will be used to compare the time to a
negative saliva test from the start of the study between patients receiving PVP-I to
those receiving the placebo. A hazard ratio of >1 will favor treatment with PVP-I,
calculated with a 95% confidence interval by Cox proportional hazards model.

1.2. The median time to negative swab in the PVP-I group versus the control will be
statistically compared using the unpaired Mann-Whitney U test.

1.3. The proportion of patients with a negative sample will be compared between the
PVP-I group and control group at all times points using the Chi-squared test.

1.4. A subsequent risk factor analysis will be conducted using the cox proportional
hazards model, investigating the independent influence of various host and disease
factors on the time to a negative sample during the study period. The following relevant
factors included in the multivariable regression were identified a priori upon
consultation with experienced clinicians at our center: gender, age, smoking status
(yes/no), baseline viral load, known baseline lung comorbidity (yes/no) , duration of
symptoms before treatment.

2. SARS-CoV-2 viral load changes in the saliva amongst patients rinsing and gargling with
0.23% PVP-I compared to a placebo group measured during the study treatment daily for 2
weeks and at the 4-week and 6-week mark.

2.1. Logarithmic viral load levels in the saliva samples will be graphed and compared
between the PVP-I and placebo group at all time points using the unpaired Mann-Whitney U
test. For complete statistical analysis, a value of 1 log base 10 copies/mL will be
assigned to samples with undetectable viral levels.

3. Time to a negative/undetectable SARS-CoV-2 saliva sample as well as SARS-CoV-2 viral
load changes amongst patients rinsing and gargling with 0.23% PVP-I compared to the 0.6%
PVP-I gel forming nasal spray for 2 weeks and at the 4-week and 6-week mark.

3.1. Similar analysis as per 1.1, 1.2, 1.3 and 2.1 above in primary outcomes.

Secondary outcomes

1. Change in symptom scores between the PVP-I group and placebo group as assessed by the
SNOT-22 scores collected at baseline and at the 2-week, 4-week and 6-week mark.

1.1. SNOT-22 scores will be graphed and compared between baseline and each time point
for each group separately using the ANOVA with repeated measures test and Bonferroni
post hoc test.

1.2. The change in SNOT-22 scores between baseline and each time point will be compared
between groups using the unpaired Mann-Whitney U test.

2. Change in symptom scores between the PVP-I group and placebo group as assessed by the
WURSS-44 scores collected daily from baseline for 2 weeks and at the 4-week and 6-week
mark.

2.1. WURSS-44 scores will be graphed and compared between baseline, the 2 week, 4-week
and 6-week marks for each group separately using the ANOVA with repeated measures test
and Bonferroni post hoc test.

2.2. WURSS-44 scores will be graphed and compared between baseline and at all time
points using the unpaired Mann-Whitney U test.

3. The need for hospitalization between the PVP-I group and placebo group. 3.1. The
Kaplan-Meier technique will also be used to compare the need for hospitalization from
the start of the study between both groups.

4. The change in SNOT-22 scores, WURSS-44 scores and the need for hospitalization between
patients rinsing and gargling with 0.23% PVP-I compared to the 0.6% PVP-I gel forming
nasal spray.

4.1. Similar analysis as per 1.1, 1.2, 2.1, 2.2 and 3.1 above in secondary outcomes.

Descriptive statistics (mean, median, SD) will be used to describe demographic
characteristics of the patients. Results will be considered statistically significant with p
values < 0.05. All statistical analyzes will be performed using RStudio version 3.4.1
(RStudio, Boston, MA, USA).

Assessment of Safety

Safety Monitoring

Patients who experience signs and symptoms of iodine reaction will be noted and the code will
be broken so that a discussion can occur between the research supervisor and the patient
regarding the use of the topical iodine.

Patients can contact the office anytime if they notice any of the signs or symptoms of iodine
reaction and will be seen by the research supervisor (or designate) within 24 hours.

Adverse Events (AE's)

All expected and unexpected adverse events will be recorded and graded by the research
supervisor. Stable chronic conditions, which are present prior to the clinical trial entry
and do not worsen, are not considered adverse events and will be accounted for in the
patient's medical history.