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Article

Updated Clinical Evaluation of the CLUNGENE® Rapid COVID-19 Antibody Test

by
Christopher C. Lamb
1,2,3,*,
Fadi Haddad
4,5,6,
Christopher Owens
7,
Alfredo Lopez-Yunez
7,
Marion Carroll
8 and
Jordan Moncrieffe
8
1
Weatherhead School of Management, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, USA
2
Silberman College of Business, Fairleigh Dickinson University, 1000 River Rd., Teaneck, NJ 07666, USA
3
BioSolutions Services LLC, 92 Irving Avenue, Englewood Cliffs, NJ 07632, USA
4
Fellow of the Infectious Disease Society of America (IDSA), 4040 Wilson Boulevard, Suite 300, Arlington, VA 22203, USA
5
Fadi Haddad, MD, Inc., 8860 Center Dr. Suite 320, La Mesa, CA 91942, USA
6
Sharp Grossmont Hospital, 5555 Grossmont Center Dr., La Mesa, CA 91942, USA
7
Alivio Medical Center, Indianapolis, IN 46219, USA
8
MedComp Sciences, LLC, 20503 MacHost Road, Zachary, LA 70791, USA
*
Author to whom correspondence should be addressed.
Healthcare 2021, 9(9), 1124; https://doi.org/10.3390/healthcare9091124
Submission received: 30 June 2021 / Revised: 29 July 2021 / Accepted: 11 August 2021 / Published: 30 August 2021
(This article belongs to the Special Issue Novel Coronavirus (SARS-CoV-2) Outbreak: Epidemiology, Research and Implications for Public Health)
Browse Figure
Review Reports Versions Notes

Abstract

:
Background: COVID-19 antibody testing has been shown to be predictive of prior COVID-19 infection and an effective testing tool. The CLUNGENE® SARS-COV-2 VIRUS (COVID-19) IgG/IgM Rapid Test Cassette was evaluated for its utility to aide healthcare professionals. Method: Two studies were performed by using the CLUNGENE® Rapid Test. (1) An expanded Point-of-Care (POC) study at two clinical sites was conducted to evaluate 99 clinical subjects: 62 positive subjects and 37 negative subjects were compared to RT-PCR, PPA, and NPA (95% CI). Sensitivity was calculated from blood-collection time following symptom onset. (2) A cross-reactivity study was performed to determine the potential for false-positive results from other common infections. Results: The specificity of subjects with confirmed negative COVID-19 by RT-PCR was 100% (95% CI, 88.4–100.0%). The sensitivity of subjects with confirmed positive COVID-19 by RT-PCR was 96.77% (95% CI, 88.98–99.11%). In the cross-reactivity study, there were no false-positive results due to past infections or vaccinations unrelated to the SARS-CoV-2 virus. Conclusion: There is a need for a rapid, user-friendly, and inexpensive on-site monitoring system for diagnosis. The CLUNGENE® Rapid Test is a useful diagnostic test that provides results within 15 min, without high-complexity laboratory instrumentation.

1. Introduction

The COVID-19 pandemic SARS-CoV2 COVID-19 has infected over 140 million people worldwide and has caused approximately 3.89 million deaths as of 23 June 2021 [1]; however, some studies suggest that the actual number of global COVID-19 deaths may be about 6.9 million, which is more than double the recorded amount [2,3,4]. In response to the pandemic, the US Food and Drug Administration (FDA) authorized the use of COVID-19 serological tests through Emergency Use Authorizations (EUAs) to make COVID-19 in vitro diagnostic tests widely available to help identify individuals with an adaptive immune response indicating recent or prior infection [5]. Serology tests, or immunoassays, play a significant role in the fight against COVID-19 [6,7]. A prior history of SARS-CoV-2 infection is associated with a lower risk of infection, with an estimated protective effect of up to seven (7) months following primary infection; this supports the conclusion that convalescent plasma with specific antibodies to SARS-CoV-2 has powerful antiviral activity, which can reduce the viral load and mortality in patients with active COVID-19 infection [8,9,10].
There is an urgent need for a rapid, user-friendly, and inexpensive on-site monitoring system for diagnosis [11]. The CLUNGENE® SARS-COV-2 VIRUS (COVID-19) IgG/IgM Rapid (15 min) Test Cassette has been commercially available in the US under an FDA-approved Emergency Use Authorization (EUA201121) [12] and Europe (CE Mark reference 02PBJ267 dated 9 March 2020). The CLUNGENE® test has been previously studied, including the use of the test in the offices of general practitioners, evaluating the presence of antibodies in convalescent plasma donors, and how the test performs at a point of care facility [13,14,15]. The aim of this research was to better understand the sensitivity and specificity of the CLUNGENE® assay and the potential for false-positive results related to infections or vaccinations not linked to the SARS-CoV-2 virus.

2. Materials and Methods

2.1. Study #1

2.1.1. Design

In an initial study, a single Point-of-Care (POC) facility was used to estimate the sensitivity and specificity of the CLUNGENE® test [16]. The study was expanded to a second independent site. The two sites were Sharp Healthcare, a not-for-profit multi-center regional healthcare group located in San Diego, CA; and Alivio Medical Center, an urgent care/primary care center in Indianapolis, IN. Samples used for RT-PCR were nares swabs. Positive subjects were symptomatic for SAR-CoV-2 Virus infected and confirmed with RT-PCR positive tested nares swabs. Negative subjects were asymptomatic, from high-risk areas, and confirmed with negative RT-PCR tested nares swabs. Finger-prick whole-blood samples were used for SARS-COV-2 Virus IgG/IgM detection. The comparator method for RT-PCR was either Cobas Roche SARS-COV2 RT-PCR (Roche Diagnostics, 9115 Hague Road PO Box 50457, Indianapolis, IN 46250) or Thermo Fisher TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific, 168 3rd Ave, Waltham, MA 02451, USA). Trained operators with no prior information about each subject drew samples. Subject inclusion criteria included individuals with a confirmed COVID-19 test result by SARS-CoV-2 RT-PCR. Subjects were excluded if they were unable to provide informed consent due to mental or cognitive disabilities.

2.1.2. Methods

The CLUNGENE® Point-of-Care test was run according to the manufacturer’s instructions (see Figure 1). The test result was read after 15 min. Days from symptom onset were captured from an electronic medical record which documented self-reported data from patients reporting on the number of days they had been sick at the time of study enrollment.
Categorical variables were compared using the chi-squared or Fisher exact test, and continuous variables were compared using the Student t-test or Mann-Whitney U test, as appropriate. All tests were two tailed, and p < 0.05 was considered statistically significant. SPSS Statistics, IBM SPSS software, version 27.0 (SPSS, Inc., Chicago, IL, USA) was used for all calculations.
The CLUNGENE® test can be stored at ambient temperature between 4 and 30 degrees Celsius. The product is packaged in a box with 25 test kits, with each kit wrapped in an individual foil patch for proper storage and transportation. The test kit itself should be kept away from direct sunlight.

2.2. Study #2

2.2.1. Design

An initial cross-reactivity study was performed in which various common infectious agents were tested for potential false-positive results (Table 1). All tests were negative. In addition, as recommended by the US Food and Drug Administration [17], a follow-up study tested the cross-reactivity of the CLUNGENE® device to antibodies to common coronaviruses that are not SARS-CoV-2: anti-229E, anti-NL63, anti-OC43, and anti-HKU1; and those for which there is a high rate of vaccinations and/or infection in the US, i.e., anti-Haemophilus influenzae IgG and IgM. The testing was performed at Medcomp Sciences, an independent clinical medical laboratory [18].

2.2.2. Methods

The CLUNGENE® Point-of-Care test was run according to same manufacturer’s instructions as was performed with Study #1. Samples (50) used for the cross-reactivity study were obtained from Trina Bioreactives, Ag; Trina Bioreactives, Ag, (Grabenstrasse 8, 8606 Nänikon, Switzerland) is an ISO certified company providing specialized Sars-COV-2 in vitro diagnostic biomaterials [19]. The samples were collected under a protocol approved by the ethics committee of the National Medical Association, Baden-Wurttemburg, Germany (file #F-2012-027, “Plasma Samples for Studies”).
Test results were read after 15 min. Five (5) serum samples that were positive for IgM and five for IgG were analyzed in three (3) separate CLUNGENE® Point-of-Care test lots with each of the below antibodies:
  • Anti-Haemophilus influenzae IgM,
  • Anti-Haemophilus influenzae IgG,
  • IgG, anti-coronavirus 229E IgG,
  • Anti-coronavirus NL63 IgG,
  • Anti-coronavirus OC43 IgG,
  • Anti-coronavirus HKU1 IgG,
  • Anti-coronavirus 229E IgM,
  • Anti-coronavirus NL63 IgM,
  • Anti-coronavirus OC43 IgM,
  • Anti-coronavirus HKU1 IgM.
Cross-reactivity was determined by using Beckman Coulter UniCel DxI Access Immunoassay System is an in vitro diagnostic device used for the quantitative, semi-quantitative, or qualitative determination of various analyte concentrations found in human body fluids (Table 2).
All QC materials were supplied and used as indicated by the manufacturer. A minimum of 2 levels of QC were processed per run in accordance with Westgard rules for 6-sigma quality requirements. QC results must fall within 3 standard deviations of historical data, as recorded in Levy–Jennings plots by the system. All QC results were documented and verified by Clinical Laboratory Scientist before processing samples (Table 3).
Qualitative results are reported as Positive/Reactive or Negative/Non-Reactive, depending on whether the analyte in question is above or below the established signal cutoff value (S/CO). Each analyte tested may have a different cutoff value, but each cutoff value is determined during calibration of the instrument, using the value of the calibrator.

3. Results

3.1. Results of Study #1

An analysis was run on 99 patients who completed the study (Table 4).
Thirty-seven (37) patients who had negative COVID-19 RT-PCR were tested and found antibody negative by using the CLUNGENE® test (95% CI, 90.60~100.00%). Three (3) out of four (4), or 75%, of RT-PCR positive COVID-19 subjects tested prior to day 7 of symptom onset were antibody positive (95% CI, 30.06~95.44%). Twenty-three (23), or 100%, of RT-PCR positive COVID-19 subjects tested positive between day 8 and 14 from symptom onset (95% CI, 85.69~100.00%). A total of 33 out of 35, or 94.28%, of RT-PCR positive COVID-19 subjects tested positive after day 14 from symptom onset were antibody positive (95% CI, 30.06~95.44%). In all 62 patients with confirmed COVID-19 with RT-PCR, the combined sensitivity of IgM and IgG was 96.77% (95% CI, 88.98–99.11%), meaning that there was 96.77 positive agreement between a positive RT-PCR test and a positive antibody test. The specificity was 100% (95% CI, 88.4–100.0%), meaning there was 100% agreement between a negative RT-PCR test and 100% negative antibody result. These results are displayed in Table 5.
The positive predictive value can be calculated, but the result is dependent on the prevalence of disease in the community. If a test for a disease has 96.77% sensitivity and 100% specificity, and the disease prevalence is 10%, the positive predictive value (PPV) is 100%, and the negative predictive value (NPV) is 99.64%. At the time of this publication, the positivity rate for the nares SARS CoV2 RT-PCR tests was between 8.2% and 10% in San Diego, CA (San Diego County), and Indianapolis, IN (Marion Country) [20].

3.2. Results of Study #2

The test results of negative quality-control samples were all negative, and the test results of the positive quality-control samples were all positive. The consistency rate of cross-reactivity of negative samples was 100%.

4. Discussion

In the first study, the performance characteristics of CLUNGENE® were evaluated and showed a specificity of 100% and a sensitivity of 96.77%. In the second study, there were no false-positive results due to past infections or vaccinations unrelated to the SARS-CoV-2 virus. These results are in line with the new European Commission’s Medical Device Coordination Group requirements for rapid COVID-19 antibody tests and consistent with previously published results [21,22,23,24,25].
Antibody testing is a useful aid to confirm past infection [26]. Recent findings confirm that antibody testing is predictive of prior COVID-19 infection, and rapid screening methods—even from finger pricks—are effective testing tools [27]. However, we see the potential for a much broader use and recommend a combined approach that uses both RT-PCR and serological testing. The advantage of the CLUNGENE® antibody test is its simplicity, since there is no need for specialized laboratory personnel to perform and interpret results. The low rate of false positivity makes this test ideal to rule in disease and eliminate the need for further RT-PCR testing if seroconversion occurs, since the CLUNGENE® antibody test can diagnose most infected COVID-19 patients. If the test is negative, a recommendation should be made to have a follow-up RT-PCR test.
Serology testing also has the potential to monitor the presence of antibodies. Studies confirm that a prior history of SARS-CoV-2 infection is associated with a lower risk of infection, with an estimated seven (7) month protective effect [9,10]. The association of SARS-CoV-2 Seropositive Antibody Test with Risk of Future Infection has now been established [28]. It is clear that titers of IgM and IgG antibodies against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 decrease significantly between one (1) and seven (7) months, and concurrently, neutralizing activity decreases [29]. Monitoring the presence of antibodies from past infection could assist healthcare professionals in assessing the likely presence of neutralizing activity and immunity when managing patient care.
Given widespread availability, COVID-19 serology testing, similar to other infectious diseases, can now become routine [30]. Consideration should be given to adding COVID-19 antibody testing to the WHO List of Essential In Vitro Diagnostics (EDL), which now consists of 122 test categories, including most serious infectious diseases [31]. A rapid 15-min COVID-19 assay offers the ability to do this testing quickly and efficiently—tests are now available for less than $5 and routinely reimbursed in the US by public and private insurers [5].
In addition, the ability of the CLUNGENE® antibody test to detect antibodies to the coronavirus’s spike protein’s receptor binding domain means it has the potential to assess the efficacy of most vaccines, as well as convalescent plasma therapy [32]. Countries in Europe are now using antibody testing to determine if a second COVID-19 vaccine dose is required if a patient has a prior infection based on a positive antibody test [33]. Recently, airports and Blood Banks have been providing COVID-19 antibody testing services to determine whether a person has developed immunity to COVID-19 through vaccination or through contracting the virus previously [34,35]. Some countries, including China, require an antibody test. Limited evaluation of the CLUNGENE® antibody test has confirmed positive antibody test results following patients who have been vaccinated [36]. Pfizer’s recent data suggest that its vaccine is efficacious for only 6 months and that a third shot within 12 months is likely needed [37]. Furthermore, there is a potential issue regarding vaccine efficacy for recipients who do not receive a full dose; the US CDC estimates that 3% of vaccinated people who received a first dose did not receive a recommended second dose [38]. COVID-19 vaccination also fails to stimulate an immune response in many blood-cancer patients or those otherwise immunocompromised [39,40]. Additional studies are needed to confirm the efficacy of serology testing to monitor vaccine effectiveness.

Limitations

Limitations of the study include a small sample size from two geographic areas. The study also did not include special groups, such as pregnant women or children. The subjectivity of symptom reporting by patients can be a confounding factor in determining the duration of illness. Some patients may have been symptomatic for a different time period than they recalled. Lastly, the CLUNGENE® antibody test has not been compared with another test in the study.

5. Conclusions

In a pandemic crisis with significant economic and health implications, this study confirms the utility of serological testing for COVID-19 disease diagnosis providing rapid test results with a relatively high degree of sensitivity and specificity. Furthermore, given recent data regarding the relationship between positive serology and immunity, routine testing can be a useful tool to monitor antibody status for optimal patient care. Tests such as the CLUNGENE® SARS-COV-2 VIRUS (COVID-19) IgG/IgM Rapid Test Cassette can assist healthcare professionals to help identify individuals with an adaptive immune response indicating recent or prior infection, as intended by the US FDA under an EUA.

Author Contributions

Conceptualization, C.C.L.; methodology, C.C.L., F.H. and M.C.; software, F.H., C.O., M.C. and J.M.; validation, F.H., C.O., A.L.-Y. and M.C.; formal analysis, C.C.L., F.H., C.O. and M.C.; investigation, F.H., C.O., A.L.-Y., M.C. and C.C.L.; resources, all; data curation, F.H., C.O., M.C., J.M. and C.C.L.; writing—original draft preparation, C.C.L.; writing—review and editing, M.C., C.O., F.H. and A.L.-Y.; visualization, C.C.L.; supervision, C.C.L.; project administration, C.C.L.; funding acquisition, C.C.L. All authors have read and agreed to the published version of the manuscript.

Funding

This research was partially funded by Clongene and Speranza.

Institutional Review Board Statement

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board of Sharp Center for Research (protocol ID: IgG/IgM COVID19; IRB#: 2005801; 21 May 2020). This was a formal IRB approved clinical study conducted within Sharp Healthcare, a not-for-profit multicenter regional healthcare group located in San Diego, California. Subjects were included if hospitalized or recently discharged following a SARS-CoV-2 RT-PCR nares test. A study protocol and informed consent were initiated and approved by the Sharp Institutional Review Board. Subjects were included if they were >18 years of age and understood the study and its requirements. Patients who had impairment of cognition or decision-making capacity were excluded. Subjects were screened by research coordinators to determine if they had a nares SARS-CoV-2 RT-PCR test result, and then consent was requested to enroll them in the study.

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study. Written informed consent was obtained from the patient(s) to publish this paper.

Data Availability Statement

The data presented in this study are available on request from the corresponding author. The data are not publicly available.

Acknowledgments

The author acknowledges Ryan Dagenais for editorial support with the manuscript; his efforts were funded by BioSolutions Services LLC.

Conflicts of Interest

Christopher C. Lamb, PhD, has worked with the manufacturers of SARS-CoV-2 tests for Emergency Use Authorization submissions to the US FDA. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

References

  1. Our World in Data. Total Confirmed COVID-19 Deaths and Cases, World. 2021. Available online: https://ourworldindata.org/grapher/cumulative-deaths-and-cases-covid-19?country=~OWID_WRL. (accessed on 24 June 2021).
  2. IHME. COVID-19 Has Caused 6.9 Million Deaths Globally, More Than Double What Official Reports Show. 2021. Available online: http://www.healthdata.org/news-release/covid-19-has-caused-69-million-deaths-globally-more-double-what-official-reports-show (accessed on 12 August 2021).
  3. IHME. Estimation of Total Mortality Due to COVID-19. Available online: http://www.healthdata.org/special-analysis/estimation-excess-mortality-due-covid-19-and-scalars-reported-covid-19-deaths (accessed on 12 August 2021).
  4. Noh, J.; Danuser, G. Estimation of the fraction of COVID-19 infected people in US states and countries worldwide. PLoS ONE 2021, 16, e0246772. [Google Scholar] [CrossRef] [PubMed]
  5. Lamb, C. COVID-19 diagnostic testing: Lessons learned for innovative product development during a public health emergency. J. Commer. Biotechnol. 2020, 25, 52–61. [Google Scholar] [CrossRef]
  6. CDC. Interim Guidelines for COVID-19 Antibody Testing. 2020. Available online: https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antibody-tests-guidelines.html (accessed on 12 August 2021).
  7. Yang, Y.; Yang, M.; Shen, C.; Wang, F.; Yuan, J.; Li, J.; Zhang, M.; Wang, Z.; Xing, L.; Wei, J.; et al. Evaluating the accuracy of different respiratory specimens in the laboratory diagnosis and monitoring the viral shedding of 2019-nCoV infections. medRxiv 2020. [Google Scholar] [CrossRef]
  8. Bošnjak, B.; Stein, S.C.; Willenzon, S.; Cordes, A.K.; Puppe, W.; Bernhardt, G.; Ravens, I.; Ritter, C.; Schultze-Florey, C.R.; Gödecke, N.; et al. Low serum neutralizing anti-SARS-CoV-2 S antibody levels in mildly affected COVID-19 convalescent patients revealed by two different detection methods. Cell. Mol. Immunol. 2020, 18, 936–944. [Google Scholar] [CrossRef]
  9. Casadevall, A.; Dragotakes, Q.; Johnson, P.W.; Senefeld, J.W.; Klassen, S.A.; Wright, R.S.; Joyner, M.J.; Paneth, N.; Carter, R.E. Convalescent Plasma Use in the United States was inversely correlated with COVID-19 Mortality: Did Convalescent Plasma Hesitancy cost lives? medRxiv 2021. [Google Scholar] [CrossRef]
  10. European Centre for Disease Prevention and Control. Risk of SARS-CoV-2 Transmission from Newly Infected individuals with Documented Previous Infection or Vaccination. 2020. Available online: https://www.ecdc.europa.eu/sites/default/files/documents/Risk-of-transmission-and-reinfection-of-SARS-CoV-2-following-vaccination.pdf (accessed on 12 August 2021).
  11. Yadav, S.; Sadique, M.A.; Ranjan, P.; Kumar, N.; Singhal, A.; Srivastava, A.K.; Khan, R. SERS based lateral flow immunoassay for point-of-care detection of SARS-CoV-2 in clinical samples. ACS Appl. Bio Mater. 2021, 4, 2974–2995. [Google Scholar] [CrossRef]
  12. FDA. In Vitro Diagnostics EUAs-Serology and Other Adaptive Immune Response Tests for SARS-CoV-2. 2021. Available online: https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas-serology-and-other-adaptive-immune-response-tests-sars-cov-2. (accessed on 12 August 2021).
  13. Ragnesola, B.; Jin, D.; Lamb, C.C.; Shaz, B.H.; Hillyer, C.D.; Luchsinger, L.L. COVID19 antibody detection using lateral flow assay tests in a cohort of convalescent plasma donors. BMC Res. Notes 2020, 13, 1–7. [Google Scholar] [CrossRef] [PubMed]
  14. Osher, G.; Lamb, C.C.; Ibarra, Y.; Erickson-Samson, D. Observational Study of SARS-CoV-2 Antibody Immune Response in a Cohort of Patients at a North Suburban Chicago, Illinois Physician’s Practice. LymphoSign J. 2020, 7, 104–108. [Google Scholar] [CrossRef]
  15. Lamb, C.C.; Haddad, F.; Owens, C.D.; Lopez-Yunez, A.; Carroll, M.; Moncrieffe, J. Expanded Clinical Evaluation of the CLUNGENE® Rapid Covid-19 Antibody Test. J. Clin. Cell. Immunol. 2021, 12, 1–9. [Google Scholar]
  16. Haddad, F.; Lamb, C.C.; Kullar, R.; Sakoulas, G. Point-Of-Care Clinical Evaluation of the Clungene® SARS-CoV-2 Virus IgG/IgM 15-minute rapid test cassette with the Cobas® Roche RT-PCR platform in patients with or without Covid-19. LymphoSign J. 2021. [Google Scholar] [CrossRef]
  17. FDA. In Vitro Diagnostics EUAs. 2021. Available online: https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas (accessed on 12 August 2021).
  18. MedComp Sciences. 2021. Available online: https://medcompsciences.com/ (accessed on 12 August 2021).
  19. Trina Bioreactives Ag. 2021. Available online: https://trinabio.com/ (accessed on 12 August 2021).
  20. SanDiegoCounty.gov. COVID-19 in San Diego County. 2021. Available online: https://www.sandiegocounty.gov/content/sdc/hhsa/programs/phs/community_epidemiology/dc/2019-nCoV/status.html (accessed on 12 August 2021).
  21. European Commission. MDCG 2021-2: Guidance on State of the Art of COVID-19 Rapid Antibody Tests. 2021. Available online: https://ec.europa.eu/health/sites/health/files/md_sector/docs/mdcg_2021-2_en.pdf. (accessed on 12 August 2021).
  22. Flower, B.; Brown, J.C.; Simmons, B.; Moshe, M.; Frise, R.; Penn, R.; Kugathasan, R.; Petersen, C.; Daunt, A.; Ashby, D.; et al. Clinical and laboratory evaluation of SARS-CoV-2 lateral flow assays for use in a national COVID-19 seroprevalence survey. Thorax 2020, 75, 1082–1088. [Google Scholar] [CrossRef] [PubMed]
  23. Nicol, T.; Lefeuvre, C.; Serri, O.; Pivert, A.; Joubaud, F.; Dubée, V.; Kouatchet, A.; Ducancelle, A.; Lunel-Fabiani, F.; Le Guillou-Guillemette, H. Assessment of SARS-CoV-2 serological tests for the diagnosis of COVID-19 through the evaluation of three immunoassays: Two automated immunoassays (Euroimmun and Abbott) and one rapid lateral flow immunoassay (NG Biotech). J. Clin. Virol. 2020, 129, 104511. [Google Scholar] [CrossRef] [PubMed]
  24. Wu, J.L.; Tseng, W.P.; Lin, C.H.; Lee, T.F.; Chung, M.Y.; Huang, C.H.; Chen, S.Y.; Hsueh, P.R.; Chen, S.C. Four point-of-care lateral flow immunoassays for diagnosis of COVID-19 and for assessing dynamics of antibody responses to SARS-CoV-2. J. Infect. 2020, 81, 435–442. [Google Scholar] [CrossRef]
  25. Zhu, X.; Wang, X.; Han, L.; Chen, T.; Wang, L.; Li, H.; Li, S.; He, L.; Fu, X.; Chen, S.; et al. Multiplex reverse transcription loop-mediated isothermal amplification combined with nanoparticle-based lateral flow biosensor for the diagnosis of COVID-19. Biosens. Bioelectron. 2020, 166, 112437. [Google Scholar] [CrossRef] [PubMed]
  26. Deeks, J.J.; Dinnes, J.; Takwoingi, Y.; Davenport, C.; Spijker, R.; Taylor-Phillips, S.; Adriano, A.; Beese, S.; Dretzke, J.; di Ruffano, L.F.; et al. Antibody tests for identification of current and past infection with SARS-CoV-2. Cochrane Database Syst. Rev. 2020, 6, CD013652. [Google Scholar] [CrossRef]
  27. Michigan Medicine. COVID-19 Antibody Tests, Even Rapid Finger Pricks, are Effective, New Study Finds. 2021. Available online: https://www.sciencedaily.com/releases/2021/03/210331173736.htm (accessed on 12 August 2021).
  28. Harvey, R.A.; Rassen, J.A.; Kabelac, C.A.; Turenne, W.; Leonard, S.; Klesh, R.; Meyer, W.A.; Kaufman, H.W.; Anderson, S.; Cohen, O.; et al. Association of SARS-CoV-2 seropositive antibody test with risk of future infection. JAMA Intern. Med. 2021, 181, 672–679. [Google Scholar] [CrossRef] [PubMed]
  29. Gaebler, C.; Wang, Z.; Lorenzi, J.C.; Muecksch, F.; Finkin, S.; Tokuyama, M.; Cho, A.; Jankovic, M.; Schaefer-Babajew, D.; Oliveira, T.Y.; et al. Evolution of antibody immunity to SARS-CoV-2. Nature 2021, 591, 639–644. [Google Scholar] [CrossRef]
  30. John Hopkins Medicine. Immunology and Serology. 2021. Available online: https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/immunology-and-serology (accessed on 12 August 2021).
  31. World Health Organization. Second WHO Model List of Essential In Vitro Diagnostics; World Health Organization: Genève, Switserland, 2019. [Google Scholar]
  32. Saluzzo, F.; Mantegani, P.; De Chaurand, V.P.; Quaresima, V.; Cugnata, F.; Di Serio, C.; Macé, A.; De Vos, M.; Sacks, J.A.; Cirillo, D.M. SARS-CoV-2 antibodies rapid tests: A valuable epidemiological tool in challenging settings. medRxiv 2021. [Google Scholar] [CrossRef]
  33. Aan de minister van Volksgezondheid, Welzijn en Sport. Verder uitstellen van de tweede dosis dan wel inzet van één dosis. 2021. Available online: https://www.alspatientsconnected.com/wp-content/uploads/2021/04/20210308-Advies-spoedvragen-VWS_COVID-19-vaccinatie-1-1.pdf (accessed on 27 August 2021).
  34. Mcglynn, M. New Covid Antibody Testing Service Opens at Shannon Airport. 2021. Available online: https://www.irishexaminer.com/news/munster/arid-40255340.html (accessed on 12 August 2021).
  35. The Blood Connection. NEW COVID-19 Antibody Testing. 2021. Available online: https://thebloodconnection.org/antibody-testing/ (accessed on 12 August 2021).
  36. Schipol.nl. Rapid Tests at Schiphol: Take a COVID-19 Test before Departure. 2021. Available online: https://www.schiphol.nl/en/page/testing-at-schiphol/ (accessed on 12 August 2021).
  37. Pfizer. Pfizer and Biontech Confirm High Efficacy and No Serious Safety Concerns through up to Six Months Following Second Dose in Updated Topline Analysis of Landmark Covid-19 Vaccine Study. 2021. Available online: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-confirm-high-efficacy-and-no-serious (accessed on 12 August 2021).
  38. Kriss, J.L.; Reynolds, L.E.; Wang, A.; Stokley, S.; Cole, M.M.; Harris, L.Q.; Shaw, L.K.; Black, C.L.; Singleton, J.A.; Fitter, D.L.; et al. COVID-19–Vaccine Second-Dose Completion and Interval Between First and Second Doses Among Vaccinated Persons—United States, December 14, 2020−February 14, 2021. Morb. Mortal. Wkly. Rep. 2021, 70, 389–395. [Google Scholar] [CrossRef]
  39. Agha, M.; Blake, M.; Chilleo, C.; Wells, A.; Haidar, G. Suboptimal response to COVID-19 mRNA vaccines in hematologic malignancies patients. MedRxiv 2021. [Google Scholar] [CrossRef]
  40. Mehta, V.; Goel, S.; Kabarriti, R.; Cole, D.; Goldfinger, M.; Acuna-Villaorduna, A.; Pradhan, K.; Thota, R.; Reissman, S.; Sparano, J.A.; et al. Case Fatality Rate of Cancer Patients with COVID-19 in a New York Hospital System. Cancer Discov. 2020, 10, 935–941. [Google Scholar] [CrossRef] [PubMed]
Healthcare 09 01124 g001 550
Figure 1. CLUNGENE® Point-of-Care test manufacturer’s instructions.
Figure 1. CLUNGENE® Point-of-Care test manufacturer’s instructions.
Healthcare 09 01124 g001
Table
Table 1. Common infectious agents used in cross-reactivity study.
Table 1. Common infectious agents used in cross-reactivity study.
Analog
Anti-HBe, anti-HBc and HBsAg
Anti-Hepatitis C Virus (HCV)
Anti-Human Immunodeficiency Virus (HIV)-1
Anti-HIV-2
Anti-influenza A IgG
Anti-influenza B IgG
Anti-influenza A IgM
Anti-influenza B IgM
Anti-respiratory syncytial virus (RSV) IgG
Anti-respiratory syncytial virus (RSV) IgM
Anti-Mycoplasma pneumoniae (MP) IgM
Anti-Chlamydia pneumoniae (CP) IgM
Human parainfluenza virus PCR positive (Paired Convalescent)
Anti-Treponema pallidum (TP)
Rheumatoid factor (RF) 521.00 IU/mL
RF 342.50 IU/mL
RF 347.00 IU/mL
RF 310.00 IU/mL
RF 565.00 IU/mL
RF 125.00IU/mL
RF 796.00 IU/mL
RF 500.00 IU/mL
RF 825.00 IU/mL
RF 144.00 IU/mL
RF 158.00 IU/mL
RF 122.00 IU/mL
RF 197.00 IU/mL
RF 146.00 IU/mL
Antinuclear antibodies (ANA) 1:240
Common human pathogenic coronaviruses:
HCoV-HKU1
HCoV-NL63
HCoV-OC43
HCoV-229E
Table
Table 2. Reagents: reference numbers C58961 and C58957 Beckman Coulter Immunoassay System.
Table 2. Reagents: reference numbers C58961 and C58957 Beckman Coulter Immunoassay System.
ReagentReference NumberMaterial Type
Access SARS-CoV-2 IgG CalibratorRef. No. C58963
Access SARS-CoV-2 IgG CalibratorRef. No. C58958
Access SARS-CoV-2 IgG QCRef. No. C58964Quality Control (QC)
Access SARS-CoV-2 IgM QCRef. No. C58959Quality Control (QC)
Access SubstrateRef. No. 81906Quality Control (QC)
Access Wash Buffer IIRef. No. A16792Quality Control (QC)
UniCel DxI Wash Buffer IIRef. No. A16793Quality Control (QC)
Table
Table 3. Quality control for DXI600 analysis of cross-reactivity.
Table 3. Quality control for DXI600 analysis of cross-reactivity.
Rack/Pos.Sample ID Patient/Lot IDType DilutionTestCalibrator Results 1RLUs 2Completion
207/1COV-2IgG QC1 922605SerumCOV2GNon-Reactive0.02 S/CO714327 April 2021 10:20 AM
207/2COV-2IgG QC2 922605BSerumCOV2GReactive2.49 S/CO99525527 April 2021
10:20 AM
207/3COV-2IgM QC1 922821SerumCOV2MNon-Reactive0.16 S/CO1122027 April 2021
10:27 AM
COV2M(2)Non-Reactive0.16 S/CO1105327 April 2021
10:27 AM
207/4COV-2IgM
QC2 922821		SerumCOV2MReactive4.23 S/CO30147127 April 2021
10:28 AM
COV2M(2)Reactive2.62 S/CO18685427 April 2021
10:27 AM
1 S/CO: Signal/Cutoff. 2 RLUs: Relative Light Units.
Table
Table 4. Antibody percent agreement.
Table 4. Antibody percent agreement.
GroupDays Post
Symptom Onset		#PCR TotalCandidate Device Results
ResultsPPA95% CI
IgG Positive0~74250.00%15.00~85.00%
8~142323100.00%85.69~100.00%
≥15353394.28%81.39~98.42%
Total625893.55%84.55~97.46%
IgM Positive0~74375.00%30.06~95.44%
8~14232191.30%73.21~97.58%
≥15352777.14%60.98~87.93%
Total625182.26%70.96~89.79%
IgG/IgM Combined Antibody Positive0~74375.00%30.06~95.44%
8~142323100.00%85.69~100.00%
≥15353497.14%85.47~99.49%
Total626096.77%88.98~99.11%
IgG NegativeN/A3737100.00%90.60~100.00%
Table
Table 5. Line Table Data.
Table 5. Line Table Data.
# and SiteSubject IDAgeGender
(F/M)		Whole Blood Specimen Collection DateDays after Symptom OnsetCLUNGENE® Rapid Test Result
(Pos/Neg)		PCR Test DatePCR
Confirmation Result
IgMIgG
1a007sgh66F1 June 2020 NegNeg30 May 2020Neg
2a008sgh65F1 June 2020 NegNeg29 May 2020Neg
3a009sgh72M1 June 2020 NegNeg31 May 2020Neg
4a010sgh67F5 June 2020 NegNeg27 May 2020Neg
5a011sgh44M5 June 2020 NegNeg1 June 2020Neg
6a012sgh31F5 June 2020 NegNeg1 June 2020Neg
7a013sgh77F5 June 2020 NegNeg1 June 2020Neg
8a024smh37M5 June 202011NegPos2 June 2020Pos
9a025sgh89M5 June 2020 NegNeg11 June 2020Neg
10a023sgh91F6 June 2020 NegNeg9 June 2020Neg
11a024sgh81M8 June 2020 NegNeg9 June 2020Neg
12a026sgh59M8 June 2020 NegNeg11 June 2020Neg
13a019sgh69F9 June 202020NegPos23 May 2020Pos
14a028sgh58M10 June 2020 NegNeg11 June 2020Neg
15a021sgh63F11 June 202013NegPos6 June 2020Pos
16a027sgh77F11 June 2020 NegNeg1 June 2020Neg
17a029sgh29M12 June 20208PosPos8 June 2020Pos
18a033sgh69M12 June 2020 NegNeg5 June 2020Neg
19a034sgh53M12 June 2020 NegNeg11 June 2020Neg
20a035sgh77M12 June 2020 NegNeg11 June 2020Neg
21a036sgh74M12 June 2020 NegNeg10 June 2020Neg
22a037sgh30F12 June 2020 NegNeg9 June 2020Neg
23a038sgh22M12 June 2020 NegNeg6 June 2020Neg
24a001sgh38M15 June 202026PosPos23 May 2020Pos
25a006sgh53M18 June 202023NegPos29 May 2020Pos
26a027smh47M18 June 202014PosPos14 June 2020Pos
27a039sgh60M18 June 202013PosPos14 June 2020Pos
28a043sgh22F18 June 202018NegPos14 June 2020Pos
29a040sgh70M19 June 202017PosPos12 June 2020Pos
30a044sgh32F19 June 2020 NegNeg17 June 2020Neg
31a045sgh66M19 June 2020 NegNeg10 June 2020Neg
32a046sgh65M19 June 2020 NegNeg9 June 2020Neg
33a050sgh31M26 June 20208PosPos18 June 2020Pos
34a051sgh44M26 June 202010PosPos21 June 2020Pos
35a052sgh35M26 June 20207PosPos19 June 2020Pos
36a055sgh57M26 June 2020 NegNeg21 June 2020Neg
37a056sgh69F26 June 2020 NegNeg22 June 2020Neg
38a057sgh67M26 June 2020 NegNeg21 June 2020Neg
39a058sgh59F26 June 2020 NegNeg17 June 2020Neg
40a059sgh39M26 June 20206NegNeg20 June 2020Pos
41a060sgh28F26 June 2020 NegNeg24 June 2020Neg
42a061sgh51F26 June 2020 NegNeg23 June 2020Neg
43a062sgh71F26 June 202011PosPos23 June 2020Pos
44a072sgh62M2 July 202017PosPos15 June 2020Pos
45a031smh31F2 July 202022PosPos11 June 2020Pos
46a066sgh43F2 July 202015PosNeg24 June 2020Pos
47a068sgh60M2 July 202012PosPos25 June 2020Pos
48a075sgh62F2 July 20207PosPos25 June 2020Pos
49a081sgh73M9 July 20209PosPos4 July 2020Pos
50a082sgh63M9 July 202011PosPos3 July 2020Pos
51a084sgh68M9 July 202015PosPos2 July 2020Pos
52a088sgh56F9 July 202010PosPos7 July 2020Pos
53a090sgh88F9 July 202020NegPos7 July 2020Pos
54a089sgh56F17 July 202016PosPos4 July 2020Pos
55a094sgh19F17 July 202015PosPos11 July 2020Pos
56a096sgh36M17 July 202027PosPos14 July 2020Pos
57a097sghunknownF17 July 2020 NegNeg14 July 2020Neg
58a098sghunknownM17 July 2020 NegNeg8 July 2020Neg
59a099sgh48F21 July 20209PosPos18 July 2020Pos
60a100sgh48F21 July 202014PosPos17 July 2020Pos
61a101sgh72M21 July 202016NegNeg25 July 2020Pos
62a053sgh50F23 July 202027NegPos26 June 2020Pos
63a073sgh38M23 July 202034PosPos30 June 2020Pos
64a103sgh29M24 July 202012PosPos15 July 2020Pos
65a104sgh40M24 July 202021PosPos11 July 2020Pos
66a106sgh45M28 July 202015NegPos22 July 2020Pos
67a113sgh46F31 July 20207PosNeg25 July 2020Pos
68a114sgh79F4 August 202012PosPos30 July 2020Pos
69a110sgh51F5 August 202015PosPos29 July 2020Pos
70a109sgh63M7 August 202019PosPos25 July 2020Pos
71a119sgh60F8 August 202010PosPos7 August 2020Pos
72a105sgh38M12 August 202031PosPos20 July 2020Pos
73a120sgh73M13 August 202022PosPos26 July 2020Pos
74a123sgh47M13 August 202012PosPos10 August 2020Pos
75a124sgh80M13 August 202030PosPos20 July 2020Pos
76a118sgh94F14 August 202015NegPos31 July 2020Pos
77a117sgh28F14 August 202014PosPos5 August 2020Pos
78a121sgh62F17 August 202014PosPos12 August 2020Pos
1bC01129F12 December 202014PosPos30 November 2020Pos
2bA00544F12 December 2020 NegNeg6 December 2020Neg
3bC02030F12 December 202014PosPos28 November 2020Pos
4bC01252M14 December 202014PosPos5 December 2020Pos
5bC03246M14 December 2020 NegNeg10 December 2020Neg
6bC03318M14 December 2020 NegNeg10 December 2020Neg
7bC00474M19 December 202026PosPos3 December 2020Pos
8bC03028M19 December 2020 NegNeg16 December 2020Neg
9bC01639F21 December 202019PosPos10 December 2020Pos
10bC03118F21 December 2020 NegNeg16 December 2020Neg
11bC00953F29 December 202018PosPos19 December 2020Pos
12bC01055M29 December 202019PosPos19 December 2020Pos
13bC02846M29 December 202024PosPos18 December 2020Pos
14bC00519F31 December 202021PosPos18 December 2020Pos
15bC00619F31 December 202021PosPos18 December 2020Pos
16bC00742F31 December 202021PosPos18 December 2020Pos
17bC01942F31 December 202015PosPos18 December 2020Pos
18bC02651F31 December 2020 NegNeg31 December 2020Neg
19bC02743F31 December 2020 NegNeg31 December 2020Neg
20bC02954M31 December 202015PosPos26 December 2020Pos
21bC01340M4 January 202128PosPos15 December 2020Pos
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MDPI and ACS Style

Lamb, C.C.; Haddad, F.; Owens, C.; Lopez-Yunez, A.; Carroll, M.; Moncrieffe, J. Updated Clinical Evaluation of the CLUNGENE® Rapid COVID-19 Antibody Test. Healthcare 2021, 9, 1124. https://doi.org/10.3390/healthcare9091124

AMA Style

Lamb CC, Haddad F, Owens C, Lopez-Yunez A, Carroll M, Moncrieffe J. Updated Clinical Evaluation of the CLUNGENE® Rapid COVID-19 Antibody Test. Healthcare. 2021; 9(9):1124. https://doi.org/10.3390/healthcare9091124

Chicago/Turabian Style

Lamb, Christopher C., Fadi Haddad, Christopher Owens, Alfredo Lopez-Yunez, Marion Carroll, and Jordan Moncrieffe. 2021. "Updated Clinical Evaluation of the CLUNGENE® Rapid COVID-19 Antibody Test" Healthcare 9, no. 9: 1124. https://doi.org/10.3390/healthcare9091124

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