COVID-Antibody: Rapid SARS-CoV-2 IgG Antibody Testing in High Risk Healthcare Workers

Sponsor
Indiana University (Other)
Overall Status
Completed
CT.gov ID
NCT04334876
Collaborator
(none)
571
1
1
9
63.2

Study Details

Study Description

Brief Summary

The purpose of this study is to validate the use of a rapid, at home, point-of-care (POC) SARS-CoV-2 IgG antibody test in high risk healthcare workers. Additionally, we would like to evaluate the incidence of seroconversion in this high-risk population and to identify possible candidates for convalescent plasma donation for therapy/prophylaxis.

Condition or Disease Intervention/Treatment Phase
  • Diagnostic Test: SARS-CoV-2 IgG Antibody Testing Kit
N/A

Detailed Description

The success of Singapore, Taiwan and Hong Kong in limiting the impact of the sudden acute respiratory syndrome coronavirus-2 (SARS-CoV-2), also know as COVID-19, has been attributed to their preparedness but mostly to the implementation and distribution of SARS-CoV-2 fast diagnostic tests and establishment of decentralized point-of-care (POC) testing (https://www.nature.com/articles/d41587-020-00010-2). So far, the frontline response to the SARS-CoV-2 outbreak has been polymerase chain reaction (PCR) testing. PCR is the gold standard for diagnosing an infectious agent, and it has the advantage that the primers needed for such tests can be produced with relative speed as soon as the viral sequence is known.

The first quantitative reverse-transcriptase-based PCR (RT-PCR) tests for detecting SARS-CoV2 were designed and distributed in January by the World Health Organization (WHO), soon after the virus was identified. The test protocol is complex and expensive, however, and is mainly suited to large, centralized diagnostic laboratories. Tests typically take 4-6 hours to complete, but the logistical requirement to ship clinical samples means the turnaround time is 24 hours at best. A new fast PCR test (45 min) from Cepheid has been approved by the U.S. Food and Drug Administration on March 21st with availability at the end of the month. Rapid POC tests are also needed to accelerate clinical decision-making and to take some of the workload off centralized test laboratories. Most importantly, the current state of the matter in Indiana University Health system, as well as many around the country is that healthcare workers including from the ER and ICU are currently unable to receive adequate testing through existing facilities. Worst, their access to appropriate personal protective equipment (PPE) has been limited, increasing their exposure risk and causing a significant amount of stress and anxiety for front-line healthcare providers across the country.

Back to the Singapore experience, they have used immunoassays that can provide historic information about viral exposure, as well as diagnostic evidence. They exploited antibody-antigen recognition, either by using monoclonal antibodies (mAbs) to detect viral antigens in clinical samples or by using cloned viral antigens to detect patient antibodies directed against the virus. The lateral flow assay format - essentially a dipstick encased in a cassette - contains the capture reagents (either an mAb directed at a viral antigen or a viral antigen that is recognized by patients' antibodies) immobilized at defined locations on a nitrocellulose membrane, as well as labelled detector mAbs that recognize the same target. A positive result, which is triggered by binding between the analyte and capture mAb and binding by the detector mAb, is visible as a colored line. Two drops of blood from a pinprick is enough to detect a virus. They're essentially the same as home pregnancy kits. Several of these assays are available in Asia, and most European Countries have been using them too. In US, RayBiotech has developed such a similar test using knowledge from the Asian tests (https://www.raybiotech.com/covid-19-igm-igg-rapid-test-kit/). This product is CE marked and certified for diagnostic use in the EU. The application for FDA Emergency Use Authorizations of tests was submitted on March 16th, 2020. At the moment, the FDA has only approved PCR testing. No lateral flow tests have been approved as of March 23rd, 2020. However, this lateral flow test can be used legally in the US, for in vitro diagnostic use, as a POC test when administered by a licensed medical practitioner. These kits were developed in-house by Ray Biotech and validated using samples taken in hospital from patients showing clinical symptoms in Guangzhou China (all confirmed via PCR). Current stocks of 10,000 kits are being replenished daily at RayBiotech, with efforts to increase production ten-fold within the next week. The CE certificate can be found here: https://www.raybiotech.com/files/images/CG-COV_CE-Certificates.jpg.

Based on the Singapore, Taiwan, Hong Kong positive experience, and to curb the fast spread of the virus in the US, we propose to use the POC SARS-CoV-2 IgG Antibody in high risk healthcare workers with or without symptoms, previously quarantine or not. Indeed, we hypothesize that the incidence of seroconversion among ER and ICU healthcare workers is high and higher than current models predict and that several cases are asymptomatic or with mild symptoms.

There are two additional benefits of testing seroconversion.

  1. Although there are no official reports, we clearly hear and see selfies of anxiety, stress and exhaustion from our colleagues at the front line. Thus for the healthcare workers knowing that they have seroconverted, will help them be more confident that they are now protected and can work in safer conditions as it has recently been shown that reinfection could not occur in SARS-CoV-2 infected rhesus macaques https://www.biorxiv.org/content/10.1101/2020.03.13.990226v1.

  2. The healthcare workers represent an ideal pool of donors for convalescent plasma due to their commitment and the fact that they have usually been tested to give blood or are currently blood donors. The FDA just approved a master protocol for collection and administration of convalescent plasma: https://www.fda.gov/vaccines-blood-biologics/investigational-new-drug-ind-or-device-exem ption-ide-process-cber/investigational-covid-19-convalescent-plasma-emergency-inds

In sum, "you cannot fight a fire blindfolded, and we cannot stop this pandemic if we don't know who is infected." (World Health Organization Director-General, 16 March 2020).

If successful and validated, we will hope to rapidly scale it up to propose the rapid SARS-CoV-2 IgG Antibody testing to the general population as has been done in countries that have had almost no death due to COVID-19.

Study Design

Study Type:
Interventional
Actual Enrollment :
571 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Diagnostic
Official Title:
Rapid SARS-CoV-2 IgG Antibody Testing in High Risk Healthcare Workers and Candidacy for Convalescent Plasma Therapy/Prophylaxis
Actual Study Start Date :
Apr 1, 2020
Actual Primary Completion Date :
Nov 1, 2020
Actual Study Completion Date :
Jan 1, 2021

Arms and Interventions

Arm Intervention/Treatment
Other: High Risk Healthcare Workers

At home, finger prick, antibody test.

Diagnostic Test: SARS-CoV-2 IgG Antibody Testing Kit
A, finger prick, at home test for SARS-CoV-2 IgG Antibodies.
Other Names:
  • Ray Biotech
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Participant Health Care Workers With a Positive Rapid, At-home, Point-of-care (POC) SARS-CoV2 IgG Antibody Test. [Subjects self-administered the at home POC test and self-reported at their convenience. Testing/reported took approx 15min. Follow up at home testing allowed q 3 weeks post-reporting for a total of 3 at-home tests possible]

      To determine the number of high risk health care workers with a positive SARS CoV2 IgG on a rapid, at home, self-administered, point-of-care (POC) test. Positive POC tests were then assessed for confirmation using a serum antibody test.

    Secondary Outcome Measures

    1. Number of Healthcare Workers Willing to be Convalescent Plasma Donors if Appropriate [Enrollment open from April 2020-January 2021. Subjects completed survey at time of submitting the results of the at home POC test. Survey questioned willingness to donate plasma if found to have antibodies to SARS Co-V2.]

      To identify possible candidates for convalescent plasma donation for therapy/prophylaxis

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. High risk healthcare workers, prioritizing those who are exposed to aerosol generating procedures (physicians and respiratory therapist) working in the emergency room or intensive care units at Indiana University Health or IU school of Medicine affiliated facilities. A second tier of prioritization, to be approached if testing capacity remains after the initial testing phase, will be nurses working these same areas

    2. Health care workers who are currently out sick or quarantined due to possible/known exposure to COVID-19 and whose physician confirms that a negative test would allow their return to work are also eligible for testing (Subjects in this group may begin study procedures and be registered once they reach the end of their quarantine period)

    Exclusion Criteria:
    1. Previously tested for COVID-19

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Indiana University Health Hospital Indianapolis Indiana United States 46202

    Sponsors and Collaborators

    • Indiana University

    Investigators

    • Principal Investigator: Courtney Rowan, MD, Indiana University

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Courtney Rowan, MD, Indiana University
    ClinicalTrials.gov Identifier:
    NCT04334876
    Other Study ID Numbers:
    • 2003973826
    First Posted:
    Apr 6, 2020
    Last Update Posted:
    Sep 16, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    Yes
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Inclusion criteria included High risk healthcare workers, prioritizing those working in the emergency room or intensive care units. A second tier of prioritization, was approached after the initial testing phase, which included expansion to other workers within the healthcare system. We excluded those that had previously tested positive for COVID-19
    Pre-assignment Detail
    Arm/Group Title High Risk Healthcare Workers
    Arm/Group Description At home, finger prick, antibody test. SARS-CoV-2 IgG Antibody Testing Kit: A, finger prick, at home test for SARS-CoV-2 IgG Antibodies.
    Period Title: Overall Study
    STARTED 571
    COMPLETED 500
    NOT COMPLETED 71

    Baseline Characteristics

    Arm/Group Title High Risk Healthcare Workers
    Arm/Group Description At home, finger prick, antibody test. SARS-CoV-2 IgG Antibody Testing Kit: A, finger prick, at home test for SARS-CoV-2 IgG Antibodies.
    Overall Participants 500
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    37.5
    (10.4)
    Sex: Female, Male (Count of Participants)
    Female
    388
    77.6%
    Male
    112
    22.4%
    Race and Ethnicity Not Collected (Count of Participants)
    Region of Enrollment (Count of Participants)
    United States
    500
    100%
    Participant profession (Count of Participants)
    Physicians
    145
    29%
    Nurses
    226
    45.2%
    Respiratory therapist
    33
    6.6%
    other healthcare workers
    95
    19%
    Unknown
    1
    0.2%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participant Health Care Workers With a Positive Rapid, At-home, Point-of-care (POC) SARS-CoV2 IgG Antibody Test.
    Description To determine the number of high risk health care workers with a positive SARS CoV2 IgG on a rapid, at home, self-administered, point-of-care (POC) test. Positive POC tests were then assessed for confirmation using a serum antibody test.
    Time Frame Subjects self-administered the at home POC test and self-reported at their convenience. Testing/reported took approx 15min. Follow up at home testing allowed q 3 weeks post-reporting for a total of 3 at-home tests possible

    Outcome Measure Data

    Analysis Population Description
    There was a total of 571 subjects consented. Of these, 71 were lost to follow-up, giving a total of 500 subjects who completed the survey and submitted results for the POC test. Of these 500, 58 subjects did a second follow up point of care test, and 15 patients completed a 3rd test.
    Arm/Group Title High Risk Healthcare Workers
    Arm/Group Description At home, finger prick, antibody test. SARS-CoV-2 IgG Antibody Testing Kit: A, finger prick, at home test for SARS-CoV-2 IgG Antibodies.
    Measure Participants 500
    Count of Participants [Participants]
    8
    1.6%
    2. Secondary Outcome
    Title Number of Healthcare Workers Willing to be Convalescent Plasma Donors if Appropriate
    Description To identify possible candidates for convalescent plasma donation for therapy/prophylaxis
    Time Frame Enrollment open from April 2020-January 2021. Subjects completed survey at time of submitting the results of the at home POC test. Survey questioned willingness to donate plasma if found to have antibodies to SARS Co-V2.

    Outcome Measure Data

    Analysis Population Description
    We surveyed the number of healthcare workers who would be wiling to donate plasma if found to have positive antibodies to SARS Co-V2 IgG
    Arm/Group Title High Risk Healthcare Workers
    Arm/Group Description At home, finger prick, antibody test. SARS-CoV-2 IgG Antibody Testing Kit: A, finger prick, at home test for SARS-CoV-2 IgG Antibodies.
    Measure Participants 500
    Count of Participants [Participants]
    426
    85.2%

    Adverse Events

    Time Frame 6 months
    Adverse Event Reporting Description Participants were to report any adverse events to the research team.
    Arm/Group Title High Risk Healthcare Workers
    Arm/Group Description At home, finger prick, antibody test. SARS-CoV-2 IgG Antibody Testing Kit: A, finger prick, at home test for SARS-CoV-2 IgG Antibodies.
    All Cause Mortality
    High Risk Healthcare Workers
    Affected / at Risk (%) # Events
    Total 0/571 (0%)
    Serious Adverse Events
    High Risk Healthcare Workers
    Affected / at Risk (%) # Events
    Total 0/571 (0%)
    Other (Not Including Serious) Adverse Events
    High Risk Healthcare Workers
    Affected / at Risk (%) # Events
    Total 0/571 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Courtney Rowan
    Organization Indiana University
    Phone 317-944-7065
    Email coujohns@iu.edu
    Responsible Party:
    Courtney Rowan, MD, Indiana University
    ClinicalTrials.gov Identifier:
    NCT04334876
    Other Study ID Numbers:
    • 2003973826
    First Posted:
    Apr 6, 2020
    Last Update Posted:
    Sep 16, 2021
    Last Verified:
    Sep 1, 2021