COVID-19 Antigen Rapid Test Evaluation in Low-Prevalence Setting (CV006)

Performance Assessment of COVID-19 Antigen Rapid Diagnostic Tests and Algorithms in Low-Prevalence Settings

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting COVID-19 pandemic present important diagnostic challenges. Point-of-care tests that detect SARS-CoV-2 antigen have the potential to allow earlier detection and isolation of confirmed cases compared to PCR-based diagnostic methods, and could be implemented at Ports of Entry (PoE) to screen low-prevalence populations effectively.This study will assess the performance of available antigen Ag-RDTs such as the Panbio and Standard Q SARS-CoV-2 rapid antigen tests. Approximately 15,000 subjects entering Botswana at Ports of Entry will be enrolled over a 6-months period or more. SARS-CoV-2 RT-PCR will be used as a reference standard. A subset of participants will also be contacted, re-evaluated and re-tested at 48-72 hours following initial assessment, to assess for the impact of incubating infection on the performance of the Ag-RDTs.

In order to assess the impact of viral genetic variability on test performance, genomic sequencing will be part of the study. All SARS-CoV-2 PCR positive samples will undergo genomic sequencing to determine the virus lineages or variants.

In addition to assessing the performance of each of the Ag-RDTs, a set of testingalgorithms that could be implemented at Ports of Entry, including the sequential use of multiple Ag-RDTs with or without RT-PCR confirmation, will be assessed.

Study Overview

• Status: Completed
• Conditions: Corona Virus Infection
• Intervention / Treatment: Diagnostic test: The Abbott Panbio™ COVID-19 Ag Rapid Test

Detailed Description

Point-of-care tests to detect active SARS-CoV-2 infection have the potential to allow earlier detection and isolation of confirmed cases compared to PCR-based diagnostic methods performed in centralized laboratories, with the aim of cost-effective reduction of transmission field (Dinnes et al., 2020). In theory, sufficiently sensitive and specific point-of-care format tests could be implemented at PoE and used to screen low-prevalence populations effectively.

In particular, rapid COVID-19 antigen tests in a lateral flow format COVID antigen RDTs or AgRDTs can play a key role in accelerating access to testing and improving turnaround times for COVID-19 test results. COVID antigen RDTs detect specific proteins known as antigens on the surface of the virus and can identify people who are at the peak of infection when virus levels in the body are likely to be high. A number of AgRDTs are now available, some of which have received emergency use authorizations from the World Health Organisation (WHO) and/or the United States Food and Drug Administration (FDA). These tests have the potential to detect an active infection with performance that is close to that of PCR in specific settings. However, the performance of COVID antigen RDTs outside of highly controlled settings is not well defined,particularly in low-prevalence groups of asymptomatic people (Bryan et al., 2020; Lassaunière et al., 2020 Linares et al., 2020; Porte et al., 2020).

Antigen tests with rapid turnaround times and minimal user skill have been recently approved for emergency use listing (EUL) by the WHO. Performance data show sensitivity and specificity levels (at least 80% and 97%, respectively) sufficient for diagnostic purposes of SARS-CoV-2 in targeted individuals, but their role in population-based screening remains to be established. In this evaluation, performance characteristics of rapid SARS-COV-2 detection kits (including but not limited to the Standard Q COVID-19 Antigen Test Standard Q RDT and the Panbio™ COVID-19 Ag Rapid Test Panbio RDT, will be assessed for sensitivity, specificity, and their overall agreement with standard nucleic acid testing using polymerase chain reaction (PCR) tests. Finally, the performance of multi-test algorithms based on Ag-RDTs with or without RTPCR will be assessed for their potential use in low-prevalence screening programmes.

• Study Type: Observational
• Enrollment (Actual): 7274

Contacts and Locations

Study Locations

• Botswana
  • Gabonone
    • Gaborone, Gabonone, Botswana, 267
      • Botswana Harvard AIDS Institute Partnership

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Study participants will be enrolled at PoE at study sites within the Greater Gaborone Health District.

1. Sir Seretse Khama International Airport
2. Tlokweng, Ramotswa, Pioneer and Ramatlabana land borders Participants will be included regardless of symptoms. Individuals younger than 18 years of age or unable to provide informed consent will be excluded from the study. A subset of study subjects are expected to show evidence of negative SARS-CoV-2 RT-PCR testing within the 72 hours prior to study enrolment. These subjects will be eligible for the study; however, based on the sample size considerations described above, the number of subjects with documented negative RT-PCR testing will be capped at 1,000.

Description

Inclusion Criteria:

• In order to meet the study objectives, study recruitment will focus on the population meeting the following eligibility criteria:
• Age ≥ 18 years crossing ports of entry in Greater Gaborone Health District [including International Airport, Ports within Gaborone Health Districts ((as above)
• Able to understand the scope of the study and provided written informed consent

Exclusion Criteria:

• Participants are excluded from the study if any of the following exclusion criteria apply:
• Participants who are less than 18 years or who are unable to provide informed consent.
• Any contraindications to nasopharyngeal sample collection: recent nasal trauma or surgery, markedly deviated nasal septum, or a history of chronically blocked nasal passages or severe coagulopathy
• Vulnerable populations as deemed inappropriate for study by site PI

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
The SD Biosensor COVID-19 Ag test kit; This is one of the Investigational product or medical device(s) intended to be used with a study participant according to the study protocol	Diagnostic test: The Abbott Panbio™ COVID-19 Ag Rapid Test; This is the intervention or medical device(s) intended to be used with a study participant according to the study protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Performance characteristics of two currently available Ag-RDTs for the detection of SARS-CoV-2 antigens in nasal swabs	Point estimates of sensitivity and specificity of the COVID-19 antigen RDTs compared to the reference standard reverse transcription polymerase chain reaction when used at ports of entry	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cost estimates of Ag testing compared to PCR testing for COVID-19 case detection	(1) Cost per test performed for each of the Ag RDTs compared to RT-PCR based protocols (1) Cost per COVID-19 case detected for each of the Ag RDTs compared to RT-PCR based protocols	6 months

Collaborators and Investigators

• Sponsor: Foundation for Innovative New Diagnostics, Switzerland
• Collaborators: Botswana Harvard AIDS Institute Partnership
• Investigators: Principal Investigator: Sikulile Moyo, Phd, Botswana Harvard Aids Initiative Partneship

Publications and helpful links

General Publications

• Hussong D, Damare JM, Limpert RJ, Sladen WJ, Weiner RM, Colwell RR. Microbial impact of Canada geese (Branta canadensis) and whistling swans (Cygnus columbianus columbianus) on aquatic ecosystems. Appl Environ Microbiol. 1979 Jan;37(1):14-20. doi: 10.1128/aem.37.1.14-20.1979.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Actual): March 31, 2023
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: June 19, 2023
• First Submitted That Met QC Criteria: June 19, 2023
• First Posted (Actual): June 20, 2023

Study Record Updates

• Last Update Posted (Actual): October 12, 2023
• Last Update Submitted That Met QC Criteria: October 10, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Covid 19
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections
• Other Study ID Numbers: CV006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All manuscripts reporting FIND study data and all review articles with FIND authors should be published in an open-access, peer-reviewed journal, regardless of whether they are FIND-led or partner-led

Drug and device information, study documents

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