Impact of Nasal Saline Irrigations on Viral Load in Patients With COVID-19

Study Overview
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Brief Summary
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Nasal saline irrigations are a safe and commonly used mechanism to treat a variety of sinonasal diseases including sinusitis, rhinitis, and upper respiratory tract infections. When used properly, these irrigations are a safe and easy intervention available over the counter without a prescription. Additionally, baby shampoo has been found to be a safe additive functioning as a surfactant when a small amount is added to the saline rinses which may help augment clearance of the sinonasal cavity. While many systemic medications and treatments have been proposed for COVID-19, there has not yet been a study looking at targeted local intervention to the nasal cavity and nasopharynx where the viral load is the highest. Studies have shown that the use of simple over the counter nasal saline irrigations can decrease viral shedding in the setting of viral URIs, including the common coronavirus (not SARS-CoV-2). Further, as SARS-CoV-2 is an enveloped virus, mild-detergent application with nasal saline would neutralize the virus further. It is our hypothesis that nasal saline or nasal saline with baby shampoo irrigations may decrease viral shedding/viral load and viral transmission, secondary bacterial load, nasopharyngeal inflammation in patients infected with the novel SARS-CoV-2.

Detailed Description
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The novel coronavirus known as SARS-CoV-2 and the associated disease process COVID-19 (coronavirus disease 2019) was first seen in late 2019 in Wuhan, China. Over the following months, it quickly spread across the continent and, in short order, the globe, making an impact that hasn't been seen in generations. Although coronaviruses have been prevalent for millennia, this version is immunologically novel, and thus there is no natural immunity to the virus. This has been a major reason for its rapid spread across the world. Previous members of the coronavirus family have typically caused upper respiratory symptoms such as the common cold, though there have also been more virulent versions of this virus seen in the recent past, such as SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome). Similarly named, SARS-CoV-2 also causes upper respiratory symptoms but has varied from the previous viral syndromes in a number of ways including how quickly it has been able to transmit within a population. This is a disease that does not segregate and can affect all ages, genders, and ethnicities. Everyone is susceptible to this virus. New diagnostic and therapeutic approaches for respiratory viruses are also being rapidly developed and polymerase chain reaction-based (PCR) diagnostics and multiplex assays are increasingly used in clinical laboratories for SARS-CoV-2 clinical detection and subtyping. Rapid antigenic and genetic evolution has been expected for SARS-CoV-2 strains, and a better understanding of SARS-CoV-2 evolutionary dynamics is needed to establish an effective vaccine. Our present understanding of the nature and extent of the upper respiratory track (URT) microbiome in humans is limited. Furthermore, we have little understanding of how acute viral respiratory infections of SARS-CoV-2 influence the URT microbiome, or how genotypic differences in the virus influence the URT microbiome and vice versa. Innate immune responses to pathogens, along with dysregulation of inflammation, are key factors involved in pathogenesis, and different viral pathogens activate different types of inflammatory responses. Respiratory viral infection i.e., SARS-CoV-2 infection is expected to activate TLR2, TLR3, TLR4 and TLR7 responses and this is likely to modulate commensal microbiota populations. It is not yet known if the severity of SARS-CoV-2 disease in older adults is due to a biased host response, SARS-CoV-2 virulence determinants, or the impact infection has on commensal microbiota. Up to this point, there is no unanimously approved treatment for the disease nor is there a vaccine or antiviral drugs available for the public. The primary methods for treatment of this deadly virus have been supportive in nature including intubation in severe cases with respiratory failure. While a unanimous treatment has yet to be discovered, there has been a great amount of knowledge garnered over the last few months about the virus and the disease that accompanies it. Several studies have demonstrated high viral titers within the nasopharynx and oral cavity and many have posited that this is the primary source of infection and viral replication. Additionally, a high nasal/nasopharyngeal viral load has been associated with increased symptoms and higher severity of the disease. Interestingly, there have been a number of studies recently looking at the effect of nasal saline irrigations in the setting of viral URIs, including coronaviruses (not including SARS-CoV-2). One of the major takeaways from these studies was decreased viral shedding in patients treated with saline irrigations compared to the control group. Nasal saline irrigations are available over the counter and widely viewed as both safe and affordable. Could these irrigations have a similar effect on the novel SARS-CoV-2 that they have on other viral respiratory infections?

Official Title
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Impact of Nasal Saline Irrigations on Viral Load in Patients With COVID-19

Conditions
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COVID 19

Intervention / Treatment
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* Other: Saline Nasal Irrigation
* Other: Saline with Baby Shampoo Nasal Irrigation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients testing positive for COVID-19 at Vanderbilt University Medical Center or VUMC-associated testing centers Age of 18 years or greater Patients must be planning self-quarantine after infection in the greater Nashville area within a 30-mile radius of Vanderbilt University Medical Center Exclusion Criteria: Requiring hospitalization - only outpatient COVID-19 cases are eligible for the study Current use of nasal saline irrigations or other intranasal medications Inability to perform saline irrigations/nasal swabs in separate bathroom away from household contacts

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients enrolled will be randomized to one of three treatment groups (1. control- no intervention, 2. intervention 1 - nasal saline irrigations BID, 3. intervention 2- nasal saline irrigations with ½ teaspoon surfactant (Johnson's baby shampoo) BID).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control Group, No intervention<br>control group, no nasal irrigation | |
| Experimental: Saline Nasal Irrigation<br>Nasal irrigation BID with normal saline | Other: Saline Nasal Irrigation<br>* Saline nasal irrigation BID<br>|
| Experimental: Saline with Baby Shampoo Nasal Irrigation<br>Nasal irrigation BID with normal saline and 1/2 teaspoon baby shampoo | Other: Saline with Baby Shampoo Nasal Irrigation<br>* Saline with 1/2 teaspoon Baby Shampoo Nasal Irrigation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in SARS-CoV-2 mucosal immune response in the nasopharynx | Viral RNA will be extracted using a standard Qiagen viral RNA isolation kit. An established, high-throughput CoV genome sequencing pipeline will be used to perform overlapping long-range RT-PCR across the viral genome for each viral genome proposed in this project. | Day 1 to day 21 | 
| Change in microbial load in the nasopharynx | Evaluate microbial sequence data in the context of SARS-CoV-2 infection status to determine taxonomic profiles and their distributions within and between samples. | Day 1 to day 21 | 
| Change in Viral Load in the nasopharynx over the course of COVID-19 infection | Perform qPCR Analysis to asses viral copy number. | Day 1 to day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptom assessment | Identify symptom burden during the course of the disease via self-report | 21 days | 
| Temperature assessment | Identify temperature during the course of the disease via self-report | 21 days |