Adults (aged 18-65 years) recently diagnosed with SARS-CoV-2 infection who use a 4-day combined intervention of nasal washes with 1% baby shampoo solution and oral gargles with Listerine Antiseptic® will have a reduced SARS-CoV-2 viral load compared to those using nasal and oral washes with normal saline. This combined intervention should be acceptable, tolerable and safe in this population. To test this, investigators are conducting a trial comparing the efficacy of a number of washes in reducing the oral and nasal SARS-CoV-2 viral load among adults.

Investigators have demonstrated the in vitro viridical efficacy of both Listerine Antiseptic® and 1% dilute baby shampoo solution, a commonly used nasal rinse, against a SARS-CoV-2 surrogate and Meister et al. have similar findings with SARS-CoV-2. With an urgent need to expand the armamentarium of widely available, low-cost interventions, that are safe for repeated human use and reduce viral transmission, investigators seek to determine the impact of a combined regimen of oral and nasal rinsing with these agents on naso-oropharyngeal viral loads in adults (aged 18-65 years) with SARS-CoV-2 infection.

Rationale for the intervention: a combination of nasal washes with 1% solution of baby shampoo and oral washes with Listerine Antiseptic® Available data indicate that SARS-CoV-2 is most likely to spread, like most other common respiratory viruses, primarily through respiratory droplet transmission. With the naso-oropharynx being both the primary site from which the virus is expelled by people with infection and the nasal and oral mucosal cells is one of the sites of initial infection and viral replication. Specifically the ACE2 receptor, that SARS-CoV-2 binds for cell entry, are highly concentrated in the goblet and ciliated cells of the nose and on the tongue. Thus a reduction of viral load through topical treatment of these sites could potentially lead to reduced transmission of SARS-CoV-2.

Each of the two proposed agents to be tested have independently demonstrated virucidal activity with short contact time in vitro. With over 140 years of usage worldwide, the safety of gargles with Listerine Antiseptic® is well established. Topical nasal lavage using a dilute solution of baby shampoo has also been demonstrated to be safe and effective both as a mucoactive and microbicidal agent. Both agents are readily available and cost-efficient for daily usage.

While there are a number of ongoing trials of interventions with similar approaches, most of them focus on a single intervention, either nasal or oral rinses. This potentially leaves a viral reservoir in the untreated site, with the potential for recolonizing the entire oronasopharynx thereby limiting the utility of intervention. There is a single trial treating both the oral and nasal spaces. However, the agent being tested is povidone-iodine, that has known adverse effects limiting its use. These adverse effects include discoloration of teeth, ciliary dysfunction, iodine overdose and possible drug interactions, such as with lithium.

Investigators believe that the proposed intervention for this study is likely to be well-tolerated, highly acceptable and result in elimination from the key sites in the oronasopharynx. Additionally, the proposed four-arm design will allow investigators to compare the combined intervention with each of the component treatments. A decision was made to use saline rinses as the control arm as the investigator's in vitro data revealed that saline had no virucidal activity against human coronavirus.

Based on recent literature describing viral load dynamics during the course of SARS-CoV-2 infection, investigators believe that a four-day trial, initiated within 5 days of Covid testing, will allow for the testing of change in viral load close to/or within the 7-10 day timeframe of greatest SARS-CoV-2 viral load. The study period will also fall within the 2-3 week period of the mean duration of SARS-CoV-2. Mohamed et al suggest that 4 days of oral Listerine washes three times daily may be efficacious in decreasing viral load. Several other rinse trials also employ this rinse frequency. The rinse times of 60 secs and 30 secs for nasal wash with 1% dilute baby shampoo and oral Listerine respectively, are based on the successful virus reduction demonstrated at these contact times in vitro.

Inclusion Criteria:

1. A first-time positive test for SARS-CoV-2 infection within 5 days of enrollment
2. Adults who are ≥18 -65 years of age
3. Currently in isolation
4. Symptomatic or asymptomatic from SARS-CoV-2

Exclusion Criteria:

1. History of nasal or sinus surgery
2. Non-English speaking
3. Lack of electronic device (computer, mobile phone etc.) on which to access an app for study data collection.
4. Adults that need inpatient care for COVID-19 or any of its complications.
5. Adults that give a history of being unable to tolerate gargles or nasal washes.
6. Adults who do not give informed consent for study participation.
7. History of a Covid vaccine booster
8. A history of use of nasal or oral washes after SARS-CoV-2 test sample collection.
9. Prisoners
10. Adults that give history of current pregnancy (NO KNOWN CONTRAINDICATION TO PREGNANCY)
11. History of monoclonal antibody treatment
12. History of or current molnupiravir treatment

We plan to provide the number and proportion of the primary outcome of participants who have completed 5 days of follow up from randomization, by treatment arms to an independent biostatistician, as well as participant accrual rate, and withdrawals from study. A formal interim analysis (as detailed in the analysis section) will be completed when 67% of final sample size reaches day 5 and the results will be provided masked to the independent biostatistician, who will decide whether to halt the trial or not.