In this pilot trial, 150 confirmed COVID-19 individuals will be randomly assigned to 1 of 5 groups: distilled water, CloSYS Ultra Sensitive Rinse (Rowpar Pharmaceutical Inc., USA), Oral-B Mouth Sore (Oral-B, USA), Crest Pro-Health Multi-Protection (Crest, USA), or Listerine Zero (Johnson and Johnson, USA). Study participants will be asked to rinse/gargle with 10-20ml (according to the rinse instructions) of the assigned solutions 4 times per day, for 30-60 seconds, for 4 weeks.
SARS-CoV-2, the virus causing COVID-19, has affected vulnerable individuals, especially those
with comorbidities, and high exposure health care workers (HCWs). Typically, the virus first
colonizes in the upper respiratory tract (URT) causing clinical symptoms such as coughing,
sore throat, and then is transferred to the lower respiratory tract (LRT) which can lead to
severe pneumonia, acute respiratory distress syndrome (ARDS), sepsis, and death, if it is not
managed.
The World Health Organization (WHO) has presented comprehensive guidelines underscoring
personal hygiene measures including respiratory hygiene against SARS, MERS, influenza, and
now SARS-CoV-2 / COVID-19. While personal protection equipment (PPE), personal hygiene
measures, environmental infection control, and physical distancing are crucial in mitigating
disease transmission, respiratory hygiene measures do not prevent SARS-CoV-2 colonization in
URTs and LRTs of infected individuals (symptomatic and asymptomatic).
Experimental and clinical research studies on infections similar to COVID-19 such as SARS,
MERS, and H5N1 have shown that using antiseptic mouthwash/gargling solutions, such as
products containing chlorhexidine gluconate (CHG), polyvinylpyrrolidone iodine (PVP-I),
chlorine dioxide (ClO2), cetylpyridinium chloride (CPC), and hydrogen peroxide (H2O2) can
reduce viral load. A randomized controlled trial (N=387) showed efficacy and
cost-effectiveness of gargling with water or a product containing PVP-I (3X/day, 20 seconds)
on URTIs in healthy volunteers (18-65 years) over 60 days from a societal perspective; in
vitro studies have shown that CloSYS, an over the counter mouthwash containing ClO2, was
effective on inactivating SARS-CoV as well as disinfecting dental unit waterlines, and
biofilm control in ultrasonic dental scaling units. A recent study has shown that CloSYS
Ultra Sensitive Oral Rinse reduced the viral load of SARS CoV 2, SARS CoV, and Influenza A
H3N2 to a varying extent. The data show that the viral load reduction of SARS CoV 2 by Ultra
Sensitive rinse was 10 fold more than the reduction of SARS CoV in 30s. Recently, the US
Centers for Disease Control (CDC) and the American Dental Association (ADA) have recommended
using a mouthwash containing 1.0-1.5% H2O2 as a pre-procedural rinse before dental treatment
to potentially reduce SARS-CoV-2 load; however, no in vivo clinical studies have been
conducted to support this claim.
The aim of this pilot trial is to evaluate the effect of four over-the-counter antiseptic
mouthwash/gargling solutions compared to a control (distilled water) to reduce SARS-CoV-2
load. In addition, study participants will be assessed for the severity of their clinical
symptoms during the study period. The 4-week protocol was selected as studies have shown that
patients can continue to shed the virus and potentially transmit it to the others for a 2 to
4 week period. An interim analysis is planned when 10 participants per arm (50 total)
complete the study using the alpha-spending function with O'Brien-Fleming boundary rule.
Drug: Oral-B Mouth Sore mouthwash
Rinse and gargle 4 times daily, for 60 seconds, for 4 weeks.
Other Name: Array
Drug: Crest Pro-Health Multi-Protection mouthwash
Rinse and gargle 4 times daily, for 60 seconds, for 4 weeks.
Other Name: Array
Drug: CloSYS Ultra Sensitive Rinse mouthwash
Rinse and gargle 4 times daily, for 45 seconds, for 4 weeks.
Other Name: Array
Drug: Distilled water
Rinse and gargle 4 times daily, for 60 seconds, for 4 weeks.
Other Name: Array
Drug: Listerine Zero Mouthwash Product
Rinse and gargle 4 times daily, for 30 seconds, for 4 weeks.
Other Name: alcohol-free
Inclusion Criteria:
- Tested positive for COVID-19 with a sample collected in the prior 7 days
- Ability to read and speak English or Spanish
- Ability to participate in the study for 4 weeks
- Being asymptomatic or having mild or moderate symptoms (for example, sore throat,
coughing, fever, fatigue)
- Ability to rinse/gargle
- Not having any condition that might worsen with gargling solutions
- Not having a history of mouthwash sensitivity
- Not having an allergy to any mouthwash that has been used before
- Not using another mouthwash/gargling solution since the most recent positive test
- Not taking antimicrobial medications (antibacterial, antiviral, antibiotics including
off-label FDA-approved medications such as hydroxychloroquine)
- Anticipated ability to participate in the study for 4 weeks
- Have a cellphone and agree to receive text messages for reminders to use mouthwash
during the day and for follow-up visits, and can videoconference (like zoom) on a
cellphone, tablet, or computer for sample collection instructions
Exclusion Criteria:
- People who because of their symptoms intend to receive antiviral medications that
could potentially affect viral load in their saliva samples
- Pregnant or lactating women due to potential aversions to mouthwash solution
taste/smell.
University Of California, San Francisco
San Francisco, California, United States
Stuart A Gansky, DrPH, Principal Investigator
Professor and Lee Hysan Chair of Oral Epidemiology