COVID-19: SARS-CoV-2 Detection in Saliva, Oropharyngeal and Nasopharyngeal Specimens

Study Overview
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Brief Summary
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The aim of this study is to compare the SARS-CoV-2 detection rate using either a Saliva, oropharyngeal swabs or nasopharyngeal swab method for specimen collection.

Detailed Description
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The reference test to evaluate patients with suspected respiratory infection caused by virus is a real-time reverse transcription-polymerase chain reaction (RT-PCR) from a nasopharyngeal swab (NPS). However, other specimen collection methods like oropharyngeal swabs (OPS) and a saliva specimen collection have also been accepted by the Centers for Disease Control and Prevention for SARS-CoV-2 testing during the current coronavirus disease 19 (COVID-19) pandemic. It is unclear how much the SARS-CoV-2 detection rate differs when using different sampling methods and the aim of this study is to compare the expected COVID-19 detection rate using saliva, oropharyngeal swabs or nasopharyngeal swab in a public setting. We, therefore, aim to investigate the detection rate of SARS-CoV-2 in Saliva, oropharyngeal swab, and nasopharyngeal swab specimen samples collected in symptomatic and non-symptomatic individuals tested for COVID-19 in a public test center during the COVID-19 pandemic. Individuals referred for outpatient COVID-19 testing center will be invited to participate in a prospective clinical study. They will have saliva, OPS, and NPS specimen collection performed at the same time and analyzed separately for SARS-CoV-2. The rate for SARS-CoV-2 detection in saliva, OPS, and NPS will be compared using a logistic regression mixed-effect analysis. A Sample Size Calculation estimated that a sample of 18,000 participants would be needed for the trial with 80% power at a significance level of 5%.

Official Title
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Comparison of Detection Rate of SARS-CoV-2 in Saliva, Oropharyngeal and Nasopharyngeal Specimens in a Public COVID-19 Test Setting

Conditions
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SARS-CoV Infection, Covid19, Coronavirus

Intervention / Treatment
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* Diagnostic Test: Sequence of testing.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: volunteers, who are attending the COVID-19 test facilities to obtain a RT-PCR test. oral and written informed consent to participate before entering the study. Exclusion Criteria: Failure to understand and provide informed consent. Neck breathers (tracheostomy/laryngectomy patients) or other nasopharyngeal or oropharyngeal anomalies that do not allow for sampling using swabs.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: All participants will have Saliva collected and recieve nasopharyngeal swabs and oropharyngeal swabs for SARS-COV2. To avoid systematic bias we plan to randomize the sequence of testing.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nasopharyngeal swab, oropharyngeal swab, and salvia collection<br>The participants will first be tested with nasopharyngeal swabs followed by oropharyngeal swab and saliva collection. The collection material, virus transport medium and laboratory equipment for each method is the same in both arms | Diagnostic Test: Sequence of testing.<br>* The participants will be tested in the following sequences of sampling technique: (1) nasopharyngeal swab, oropharyngeal swab, and salvia collection OR (2) oropharyngeal swab, salvia collection, and nasopharyngeal swab OR (3) salvia collection, nasopharyngeal swab, and oropharyngeal swab. Only the sequence is different in the different arm, while the sampling technique for each method is the same in all arms.<br>|
| Active Comparator: Oropharyngeal swab, salvia collection, and nasopharyngeal swab<br>The participants will first be tested with oropharyngeal swabs followed by saliva collection and nasopharyngeal swab. The collection material, virus transport medium and laboratory equipment for each method is the same in both arms | Diagnostic Test: Sequence of testing.<br>* The participants will be tested in the following sequences of sampling technique: (1) nasopharyngeal swab, oropharyngeal swab, and salvia collection OR (2) oropharyngeal swab, salvia collection, and nasopharyngeal swab OR (3) salvia collection, nasopharyngeal swab, and oropharyngeal swab. Only the sequence is different in the different arm, while the sampling technique for each method is the same in all arms.<br>|
| Active Comparator: Salvia collection, nasopharyngeal swab, and oropharyngeal swab<br>The participants will first be tested with saliva collection followed by nasopharyngeal swab and oropharyngeal swabs. The collection material, virus transport medium and laboratory equipment for each method is the same in both arms | Diagnostic Test: Sequence of testing.<br>* The participants will be tested in the following sequences of sampling technique: (1) nasopharyngeal swab, oropharyngeal swab, and salvia collection OR (2) oropharyngeal swab, salvia collection, and nasopharyngeal swab OR (3) salvia collection, nasopharyngeal swab, and oropharyngeal swab. Only the sequence is different in the different arm, while the sampling technique for each method is the same in all arms.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SARS-CoV-2 detection rates for oropharyngeal swabs (OPS) compared with nasopharyngeal swabs and saliva collection. | Due to the high specificity of RT-PCR, we will define a participant with an RT-PCR positive result from either Saliva, OPS or NPS as having a COVID-19 infection. The combined Saliva/OPS/NPS result will therefore be used as the diagnostic reference standard to calculate the sensitivity for the Saliva, OPS and NPS tests. | 48 hours after testing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SARS-CoV-2 RT-PCR cycle threshold (Ct) values | Ct values are compared between testing methods | 48 hours after testing | 
| OPS, NPS and saliva test discomfort and likelihood to get retested | Discomfort scores (1-10) and likelihood to get retested are compared between testing methods | immediately after testing (10 minutes) | 
| Ratio of mutations in SARS-CoV-2 | Detection rate of any mutations in SARS-CoV-2 | 48 hours after testing |