Generic Testing of Antigen Tests for COVID-19 in Denmark

Agreement of Antigen Tests on Oral Pharyngeal Swabs or Less Invasive Testing With PCR, for Detecting SARS-CoV-2 in Adults: A Prospective Nationwide Observational Study

To evaluate the analytical and clinical sensitivity and specificity of antigen tests performed as oropharyngeal swabs, outer nasal swabs, saliva swabs or breath tests including self-tests for SARS-CoV-2 towards standard RT-PCR testing.

For each test 200 SARS-CoV-2 positive and 200 SARS-CoV-2 negative individuals previously defined by RT-PCR are tested. When tested an additional RT-PCR test is performed to verify status.

Analytical sensitivity and specificity is determined on 210 SARS-CoV-2 positive samples with known Cq and 100 SARS-CoV-2 negative samples.

30 companies with a total of 55 tests participate in this nationwide study.

Study Overview

• Status: Completed
• Conditions: SARS-CoV2 Infection; COVID-19 Testing
• Intervention / Treatment: Diagnostic test: Comparison of antigen tests with RT-PCR as reference method

• Study Type: Observational
• Enrollment (Actual): 4000

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Aarhus University Hospital
  • Hvidovre, Denmark, 2650
    • Hvidovre University Hospital
  • Odense, Denmark, 5000
    • Odense University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

approximately 4400 adult out-patients tested for SARS-CoV-2 by RT-PCR within 24 hours prior to inclusion.

Description

Inclusion Criteria:

• Age 18 years or over,
• Capacity to give informed, written consent
• Be able to cooperate to the additional testing.

Exclusion Criteria:

• Individuals not fulfilling the inclusion criteria
• Declining additional oropharyngeal, nasal or saliva swabs.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
SARS-Cov-2 positives; 200 individuals will be tested by each antigen test. Testing is done with up to three swabs at a time from each anatomical test location	Diagnostic test: Comparison of antigen tests with RT-PCR as reference method; Antigen tests are performed locally including sampling from multiple anatomical testing sites. A reference oropharyngeal swab is always send for RT-PCR for SARS-CoV-2 at DTU to verify the status of the patient. RT-PCR samples from other anatomical test locations may be included.
SARS-CoV-2 negatives; 200 individuals will be tested by each antigen test. Testing is done with up to three swabs at a time from each anatomical test location	Diagnostic test: Comparison of antigen tests with RT-PCR as reference method; Antigen tests are performed locally including sampling from multiple anatomical testing sites. A reference oropharyngeal swab is always send for RT-PCR for SARS-CoV-2 at DTU to verify the status of the patient. RT-PCR samples from other anatomical test locations may be included.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical sensitivity and specificity of each antigen test compared to RT-PCR test result.	Performance is compared for each antigen test in relation to oropharyngeal RT-PCR samples collected simultaneously	Up to 3 days after first initial positive COVI-19 RT-PCR test
Analytical sensitivity and specificity of each antigen test on retrospectively collected SARS-CoV-2 positive and negative samples.	SARS-CoV-2 positive samples are stratified into subgroups according to Cq by RT-PCR and frozen samples in universal transport medium is tested on each antigen test.	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical sensitivity compared to RT-PCR result with the later stratified into low, intermediate and high Cq	Performance of each antigen test in relation to the cycle of quantification Cq by RT-PCR stratified into low (Cq <25), intermediate (Cq 25-35) and High (Cq >35).	Up to 3 days after first initial positive COVI-19 RT-PCR test
Agreement between oropharyngeal swabs and tests from other anatomical test locations by RT-PCR.	Antigen an RT-PCR tests are performed from multiple anatomical sampling sites on each teste individual.	Up to 3 days after first initial positive COVI-19 RT-PCR test.

Collaborators and Investigators

• Sponsor: Hvidovre University Hospital
• Collaborators: Odense University Hospital; Aarhus University Hospital; Rigshospitalet, Denmark; Aalborg University Hospital; Herlev and Gentofte Hospital; Sygehus Lillebaelt; Statens Serum Institut; Hospital of South West Jutland; Slagelse Hospital

Publications and helpful links

General Publications

• Schneider UV, Knudsen JD, Koch A, Kirkby NS, Lisby JG. An Agreement of Antigen Tests on Oral Pharyngeal Swabs or Less Invasive Testing With Reverse Transcription Polymerase Chain Reaction for Detecting SARS-CoV-2 in Adults: Protocol for a Prospective Nationwide Observational Study. JMIR Res Protoc. 2022 May 4;11(5):e35706. doi: 10.2196/35706.

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2021
• Primary Completion (Actual): September 9, 2021
• Study Completion (Actual): September 9, 2021

Study Registration Dates

• First Submitted: May 12, 2021
• First Submitted That Met QC Criteria: May 30, 2021
• First Posted (Actual): June 4, 2021

Study Record Updates

• Last Update Posted (Actual): January 26, 2022
• Last Update Submitted That Met QC Criteria: January 24, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: RT-PCR; antigen test; Prospective samples; Retrospective samples
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: Nat COVID Ag Project

Drug and device information, study documents

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