Obstructive Sleep Apnoea Post Covid 19: Role of the Upper Airway Microbiome

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causing coronavirus disease, Covid-19, has spread rapidly across the globe since its emergence in January 2020. As of January 2021, there are 87.6 million confirmed cases worldwide, with 1.9milion deaths. In conjunction with this high disease incidence, there have also been reports of Covid-19 related sleep disordered breathing, with up 18% in a Chinese study and 57% in an Italian study of individuals with Covid-19 reporting sleep disturbance.

Obstructive Sleep Apnea (OSA) is a common, chronic condition due to partial or complete upper airway collapse during sleep. OSA is more common in males & obese individuals, both of which are more adversely affected by SARS-CoV-2 infection. Furthermore, inflammation of the upper airway, or nasal passages leading to congestion could lead to a compromised upper airway during sleep and subsequently, obstructive sleep apnea.

We believe that's SARS -CoV-2 infection, and subsequent Covid-19 will lead to an altered microbiome in the upper airway. This is turn will lead to worsening nasal inflammation and congestion, which could predispose individual with previous Covid-19 disease to OSA.

Additionally, OSA is treated with Continuous Positive Airway Pressure (CPAP) a machine which delivers pressurized air into the upper airway via a face mask. This keeps the upper airway open during sleep. When CPAP is well tolerated by individuals, it works well to reduce the symptoms of OSA. Unfortunately, many patients find it difficult to tolerate CPAP. One reason often reported for poor tolerance is nasal congestion. We believe that an altered upper airway microbiome, due to previous SARS-CoV-2 infection, will affect treatment adherence to CPAP therapy. Secondly, we will investigate if treatment with CPAP therapy causes any change in the upper airway microbiome.

Study Overview

• Status: Not yet recruiting
• Conditions: Snoring; Fatigue Syndrome, Chronic; SARS-CoV2 Infection; Sleepiness
• Intervention / Treatment: Diagnostic test: Nasal Lavage and Oral Wash

• Study Type: Observational
• Enrollment (Anticipated): 50

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants will be selected from the Sleep Clinic and Post-Covid Clinic in Beaumont Hospital. Participants with snoring and daytime somnolence requiring sleep assessment as part of routine clinical care will be selected.

Description

Inclusion Criteria:

• Symptoms of sleepiness, fatigue, loud snoring

Exclusion Criteria:

1. Gross skeletal alterations affecting the upper airway (eg.micrognathia)
2. Unstable chronic medical conditions known to affect OSA (CHF, stroke) 3.
3. Pregnancy or intent to become pregnant within the period of the protocol
4. Inability to sign informed consent form
5. Habitual snorer or previous diagnosis of OSA.
6. Less than 18 years of age.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
SARS-CoV2 OSA; Patients will be recruited from both Post-COVID19 and Sleep Clinics run through Beaumont Hospital, Beaumont, Dublin, Ireland. This will allow for the recruitment of patients with and without a history of SARS-CoV-2 infection.	Diagnostic test: Nasal Lavage and Oral Wash; Nasal Lavage: The nasal lavage will be performed using a spray technique. Using a disposable metered-dose inhaler (100 µl per spray), room temperature saline will be sprayed in one nostril while the other nostril is closed. After 5 sprays, the subject will gently exhale through the lavaged nostril and the fluid will be collected in a specimen cup. The procedure will be repeated a minimum of 8 times and a maximum of 15 times in each nostril. After collection, the sample will be placed on ice and processed within 2 hours.; Oral Rinse: Oral samples will be collected using a standardized procedure in accordance with the Manual of Procedures for Human Microbiome Project.Study participants will rinse their mouth (swish/gargle) with 15 mL sterile normal saline for 1 min, and will expectorate the contents of the mouth into a 50 mL centrifuge tube. Sample should be kept cold on ice until processing.; Other Names: Home Sleep Study; Positive Airway Pressure if diagnosed with Sleep Apnea
Non-SARS-CoV2 OSA; Patients will be recruited from both Post-COVID19 and Sleep Clinics run through Beaumont Hospital, Beaumont, Dublin, Ireland. This will allow for the recruitment of patients with and without a history of SARS-CoV-2 infection.	Diagnostic test: Nasal Lavage and Oral Wash; Nasal Lavage: The nasal lavage will be performed using a spray technique. Using a disposable metered-dose inhaler (100 µl per spray), room temperature saline will be sprayed in one nostril while the other nostril is closed. After 5 sprays, the subject will gently exhale through the lavaged nostril and the fluid will be collected in a specimen cup. The procedure will be repeated a minimum of 8 times and a maximum of 15 times in each nostril. After collection, the sample will be placed on ice and processed within 2 hours.; Oral Rinse: Oral samples will be collected using a standardized procedure in accordance with the Manual of Procedures for Human Microbiome Project.Study participants will rinse their mouth (swish/gargle) with 15 mL sterile normal saline for 1 min, and will expectorate the contents of the mouth into a 50 mL centrifuge tube. Sample should be kept cold on ice until processing.; Other Names: Home Sleep Study; Positive Airway Pressure if diagnosed with Sleep Apnea

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Examine the incidence of post SARS-CoV-2 infection obstructive sleep apnoea (OSA) and its relationships with the upper airway/nasal microenvironment	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Determine the relationship between post- SARS-CoV-2 Infection OSA, Positive Airway Pressure (PAP) treatment adherence and change in the upper airway/nasal microenvironment.	1 year

Collaborators and Investigators

• Sponsor: Royal College of Surgeons, Ireland

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): November 22, 2021
• Primary Completion (ANTICIPATED): January 1, 2023
• Study Completion (ANTICIPATED): January 1, 2023

Study Registration Dates

• First Submitted: November 10, 2021
• First Submitted That Met QC Criteria: November 10, 2021
• First Posted (ACTUAL): November 11, 2021

Study Record Updates

• Last Update Posted (ACTUAL): November 11, 2021
• Last Update Submitted That Met QC Criteria: November 10, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: obstructive sleep apnea; microbiome; sars-CoV2
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Signs and Symptoms, Respiratory; Respiratory Sounds; Encephalomyelitis; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; COVID-19; Snoring; Fatigue Syndrome, Chronic; Sleepiness
• Other Study ID Numbers: 21-031

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No