Suitability of two rapid lateral flow immunochromatographic assays for predicting SARS-CoV-2 neutralizing activity of sera

Abstract

Assessment of commercial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoassays for their capacity to provide reliable information on sera neutralizing activity is an emerging need. We evaluated the performance of two commercially available lateral flow immunochromatographic assays (LFIC; Wondfo SARS-CoV-2 Antibody test and the INNOVITA 2019-nCoV Ab test) in comparison with a SARS-CoV-2 neutralization pseudotyped assay for coronavirus disease 2019 (COVID-19) diagnosis in hospitalized patients and investigate whether the intensity of the test band in LFIC associates with neutralizing antibody (NtAb) titers. Ninety sera were included from 51 patients with moderate to severe COVID-19. A green fluorescent protein (GFP) reporter-based pseudotyped neutralization assay (vesicular stomatitis virus coated with SARS-CoV-2 spike protein) was used. Test line intensity was scored using a 4-level scale (0 to 3+). The overall sensitivity of LFIC assays was 91.1% for the Wondfo SARS-CoV-2 Antibody test, 72.2% for the INNOVITA 2019-nCoV IgG, 85.6% for the INNOVITA 2019-nCoV IgM, and 92.2% for the NtAb assay. Sensitivity increased for all assays in sera collected beyond day 14 after symptoms onset (93.9%, 79.6%, 93.9%, and 93.9%, respectively). Reactivities equal to or more intense than the positive control line (≥2+) in the Wondfo assay had a negative predictive value of 100% and a positive predictive value of 96.4% for high NtAb₅₀ titers (≥1/160). Our findings support the use of LFIC assays evaluated herein, particularly the Wondfo test, for COVID-19 diagnosis. We also find evidence that these rapid immunoassays can be used to predict high SARS-CoV-2-S NtAb₅₀ titers.

Keywords: COVID-19; SARS-CoV-2; lateral flow immunochromatographic assays; neutralizing antibodies.

Figure 1

Test line intensity was scored using a 4‐level scale. From left to right: 0, negative result; 1+, weak positive result (intensity of test band lower than the control band); 2+, positive result (intensity of test band equal to the control line); 3+, strong positive result (intensity of test band greater than the control line)

Figure 2

Median neutralizing antibody titers (NtAb₅₀) in sera from hospitalized COVID‐19 patients according to their strength of reactivity in lateral flow immunochromatographic assays (grading scale of test lines from 0 to 3+). p values for selected comparisons are shown