Combined Molecular Testing for Influenza, SARS-CoV-2, and RSV RNA From Different Upper Airway Specimens.

Study Overview
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Brief Summary
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This is a comparative prospective diagnostic accuracy study reported according to the STARD guidelines. Citizens at an outpatient COVID19 test facility at Testcenter Danmark Valby will be invited to participate in the study on a volunteer basis. The enrolled participants will have the planned oropharyngeal swab performed in the test center and sent for a SARS-CoV-2 RT-PCR test at TestCenter Danmark, Statens Serum Institut, Copenhagen, Denmark as usual. Besides the planned oropharyngeal swab performed in the test center, the participants will have additional specimens collected in form of saliva, nasopharyngeal-, nasal-, and oropharyngeal swabs. These will all be used for the detection of nucleic acids from the four most common strains of influenza (B Yamagata, B Victoria, A H1N1 and A H3N2), SARS-CoV-2 and RSV A/B. Further we will measure immune mediating cytokines, chemokines, and interleukins in the different specimens. These analyses will be performed at Technical University of Denmark (DTU).

Official Title
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Combined Molecular Testing for Influenza, SARS-CoV-2, and RSV RNA From Different Upper Airway Specimens.

Conditions
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Influenza, COVID-19, RSV Infection

Intervention / Treatment
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* Diagnostic Test: (NPS right - Nasal swab left - OPS)
* Diagnostic Test: (NPS left - Nasal swab right - OPS)
* Diagnostic Test: (Nasal swab right - NPS left - OPS)
* Diagnostic Test: (Nasal swab left - NPS right - OPS)
* Diagnostic Test: (NPS right - OPS - Nasal swab left)
* Diagnostic Test: (NPS left - OPS - Nasal swab right)
* Diagnostic Test: (Nasal swab right - OPS - NPS left)
* Diagnostic Test: (Nasal swab left - OPS - NPS right)
* Diagnostic Test: (OPS - NPS right - Nasal swab left)
* Diagnostic Test: (OPS - NPS left - Nasal swab right)
* Diagnostic Test: (OPS - Nasal swab left - NPS right)
* Diagnostic Test: (OPS - Nasal swab right - NPS left)


Participation Criteria
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Eligibility Criteria
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The inclusion criterion: A. 18 years or more of age requiring a test for COVID-19. The exclusion criteria are : A. Neck breathers (tracheostomy/laryngectomy patients) or other nasopharyngeal or oropharyngeal anomalies that do not allow for sampling using swabs. B. Do not understand oral or written Danish

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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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: Sequential Assignment
Interventional Model Description: The order of the swabs performed will be decided with randomization to either of the eight combination: NPS right - Nasal swab left - OPS NPS left - Nasal swab right - OPS Nasal swab right - NPS left - OPS Nasal swab left - NPS right - OPS NPS right - OPS - Nasal swab left NPS left - OPS - Nasal swab right Nasal swab right - OPS - NPS left Nasal swab left - OPS - NPS right OPS - NPS right - Nasal swab left OPS - NPS left - Nasal swab right OPS - Nasal swab left - NPS right OPS - Nasal swab right - NPS left
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence for upper airway specimen collection (NPS right - Nasal swab left - OPS)<br>1 NPS right - Nasal swab left - OPS NPS = nasopharyngeal swab OPS = oropharyngeal swab | Diagnostic Test: (NPS right - Nasal swab left - OPS)<br>* Collection of nasopharyngeal-, nasal-, and oropharyngeal swabs in randomized order<br>|
| Experimental: Sequence for upper airway specimen collection (NPS left - Nasal swab right - OPS)<br>2 NPS left - Nasal swab right - OPS | Diagnostic Test: (NPS left - Nasal swab right - OPS)<br>* Collection of nasopharyngeal-, nasal-, and oropharyngeal swabs in randomized order<br>|
| Experimental: Sequence for upper airway specimen collection (Nasal swab right - NPS left - OPS)<br>3 Nasal swab right - NPS left - OPS | Diagnostic Test: (Nasal swab right - NPS left - OPS)<br>* Collection of nasopharyngeal-, nasal-, and oropharyngeal swabs in randomized order<br>|
| Experimental: Sequence for upper airway specimen collection (Nasal swab left - NPS right - OPS)<br>4 Nasal swab left - NPS right - OPS | Diagnostic Test: (Nasal swab left - NPS right - OPS)<br>* Collection of nasopharyngeal-, nasal-, and oropharyngeal swabs in randomized order<br>|
| Experimental: Sequence for upper airway specimen collection (NPS right - OPS - Nasal swab left)<br>5 NPS right - OPS - Nasal swab left | Diagnostic Test: (NPS right - OPS - Nasal swab left)<br>* Collection of nasopharyngeal-, nasal-, and oropharyngeal swabs in randomized order<br>|
| Experimental: Sequence for upper airway specimen collection (NPS left - OPS - Nasal swab right)<br>6 NPS left - OPS - Nasal swab right | Diagnostic Test: (NPS left - OPS - Nasal swab right)<br>* Collection of nasopharyngeal-, nasal-, and oropharyngeal swabs in randomized order<br>|
| Experimental: Sequence for upper airway specimen collection (Nasal swab right - OPS - NPS left)<br>7 Nasal swab right - OPS - NPS left | Diagnostic Test: (Nasal swab right - OPS - NPS left)<br>* Collection of nasopharyngeal-, nasal-, and oropharyngeal swabs in randomized order<br>|
| Experimental: Sequence for upper airway specimen collection (Nasal swab left - OPS - NPS right)<br>8 Nasal swab left - OPS - NPS right | Diagnostic Test: (Nasal swab left - OPS - NPS right)<br>* Collection of nasopharyngeal-, nasal-, and oropharyngeal swabs in randomized order<br>|
| Experimental: Sequence for upper airway specimen collection (OPS - NPS right - Nasal swab left)<br>9 OPS - NPS right - Nasal swab left | Diagnostic Test: (OPS - NPS right - Nasal swab left)<br>* Collection of nasopharyngeal-, nasal-, and oropharyngeal swabs in randomized order<br>|
| Experimental: Sequence for upper airway specimen collection (OPS - NPS left - Nasal swab right)<br>10 OPS - NPS left - Nasal swab right | Diagnostic Test: (OPS - NPS left - Nasal swab right)<br>* Collection of nasopharyngeal-, nasal-, and oropharyngeal swabs in randomized order<br>|
| Experimental: Sequence for upper airway specimen collection (OPS - Nasal swab left - NPS right)<br>11 OPS - Nasal swab left - NPS right | Diagnostic Test: (OPS - Nasal swab left - NPS right)<br>* Collection of nasopharyngeal-, nasal-, and oropharyngeal swabs in randomized order<br>|
| Experimental: Sequence for upper airway specimen collection (OPS - Nasal swab right - NPS left)<br>12 OPS - Nasal swab right - NPS left | Diagnostic Test: (OPS - Nasal swab right - NPS left)<br>* Collection of nasopharyngeal-, nasal-, and oropharyngeal swabs in randomized order<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RT-PCR for upper airway viral diagnostics | the detection of nucleic acids from the four most common strains of influenza (B Yamagata, B Victoria, A H1N1 and A H3N2), SARS-CoV-2 and RSV A/B | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| local immunological mediators from the upper airway tract | measure interferon γ (IFN-γ), C-X-C motif chemokine 10 (CXCL10/IP10), interleukin 10 (IL-10), interleukin 12p70, interleukin 13 (IL-13), interleukin 1β (IL-1β), interleukin 2, interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 6, CXCL8, tumor necrosis factor α (TNF-α), C-C motif chemokine 5 (CCL5/RANTES), interferon α2a, and granulocyte macrophage colony-stimulating factor (GM-CSF). | 1 day |