Development and Performance of a Point-of-Care Rapid Antigen Test for Detection of SARS-CoV-2 Variants

Abstract

Background: SARS-CoV-2 antigen-based tests are well-calibrated to infectiousness and have a critical role to play in the COVID-19 public health response. We report the development and performance of a unique lateral flow immunoassay (LFA).

Methods: Combinations of several monoclonal antibodies targeting multiple antigenic sites on the SARS-CoV-2 nucleocapsid (N) protein were isolated, evaluated, and chosen for the development of a LFA termed CoV-SCAN (BioMedomics, Inc.). Clinical point-of-care studies in symptomatic and asymptomatic individuals were conducted to evaluate positive predictive agreement (PPA) and negative predictive agreement (NPA) with RT-PCR as comparator.

Results: In laboratory testing, CoV-SCAN detected 14 recombinant N-proteins of SARS-CoV-2 variants with sensitivity in the range of 0.2-3.2 ng/mL, and 10 authentic SARS-CoV-2 variants with sensitivity in the range of 1.6-12.5 TCID50/swab. No cross reactivity was observed with other human coronaviruses or other respiratory pathogens. In clinical point-of-care testing on 148 individuals over age 2 with symptoms of < 5 days, PPA was 87.2% (CI 95: 78.3%-94.8%) and NPA was 100% (CI 95: 94.2%-100%). In another 884 asymptomatic individuals, PPA was 85.7% (CI 95: 42.1-99.6%) and 99.7% (99.0%-99.9%). Overall, CoV-SCAN detected over 97.2% of specimens with CT values <30 and 93.8% of nasal swab specimens with the Omicron variant, even within the first 2 days after symptom onset.

Conclusions: The unique construction of CoV-SCAN using two pairs of monoclonal antibodies has resulted in a test with high performance that remains durable across multiple variants in both laboratory and clinical evaluations. CoV-SCAN should identify almost all individuals harboring infectious SARS-CoV-2.

Note:
Funding Information: The authors gratefully acknowledge support from Andrew and Peggy Cherng for all aspects of the work reported in this manuscript. In Summer 2020, NYCEDC held the Rapid Testing Innovation Competition, a request for expressions of interest that sought to identify innovative and cost-effective rapid COVID tests. CoV-Scan was identified as an outstanding candidate and Columbia University was awarded grant funding to further develop and study the test [Rapid Testing Innovation Competition to D.D.H. and M.T.Y.]; Study 2, performed at New York City Health & Hospitals, was supported by the New York Economic Development Cooperation (EDC); additional support was provided from the National Institute on Drug Abuse [U01DA053949-01 to A.U.].

Conflict of Interests: Potential conflicts of interest: MNVH, WS, ZC, BJ, FW are employed by BioMedomics, Inc, the manufacturer of the CoV-SCAN rapid antigen test. Potential conflicts of interest: DDH and LL are inventors on a patent application on monoclonal antibodies used in the construction of CoV-SCAN, and the rights to this invention has been licensed to Biomedomics by Columbia University. No other authors declare any conflict of interest.

Ethical Approval: Columbia University Irving Medical Center Institutional Review Board approved Study 1. BRANY IRB approved Study 2. All participants provided informed consent.

Keywords: SARS-CoV-2 rapid antigen tests, covid-19, Variants of concern (VOCs), Cross-reactivity