Comparison of NADAL COVID IgG/IgM rapid test and DiaSorin Liaison SARS-CoV-2 S1/S2 IgG assay across different blood sources and substrates

Abstract

The NADAL COVID-19 IgG/IgM (NADAL) assay, approved for rapid testing on serum or plasma, had not been approved nor tested as a point-of-care test on capillary blood. The study aim was to evaluate the performance of NADAL compared to that of the DiaSorin Liaison SARS-CoV-2 S1/S2 IgG (DiaSorin) assay (gold standard). We conducted two cross-sectional studies in participants aged ≥2 years, in whom different blood substrates (whole blood vs serum) and sources (venous vs capillary) were sampled. The co-primary endpoints were agreement in IgG detection between NADAL on venous serum and whole capillary blood vs DiaSorin on venous serum. Among 128 participants, 23.2% had a positive DiaSorin IgG assay. The NADAL IgG on venous serum exhibited near-perfect agreement (κ = 0.91) and high accuracy (0.94, 95% CI: 0.87-1.00), with a sensitivity of 0.88 and perfect specificity compared to DiaSorin; NADAL IgG on whole capillary blood exhibited moderate agreement (κ = 0.77) and accuracy (0.84, 95% CI: 0.73-0.95), with a sensitivity of 0.68 and perfect specificity. As for secondary outcomes, when the two assays were compared within the same source (venous or capillary) but with different substrates (NADAL on whole blood vs DiaSorin on serum), strong agreement and high accuracy were observed. Within-test DiaSorin IgG assay on capillary vs venous serum showed near-perfect agreement and high accuracy. Within-test NADAL IgG assays on whole capillary blood vs capillary or venous serum demonstrated high accuracy. In conclusion, NADAL on venous serum exhibited near-perfect agreement and high accuracy with DiaSorin on venous serum but lower between-test performance on different blood substrates.

Importance: Accurate serological assays are essential for assessing population immunity levels and identifying vulnerable subgroups with lower immunity on which to focus vaccination efforts. Although rapid tests may offer the possibility of easy point-of-care testing on whole capillary blood for these purposes, they may not be as robust as other assays when used on different blood substrates or sources than those in which they were approved. The observed variability in test performance across different substrates and blood sources highlights the importance of pretesting assays under the specific conditions in which they would be used to ensure optimal interpretation of the immune status in the community.

Keywords: NADAL COVID-19 Test; SARS-CoV-2 IgG/IgM serology; diagnostic accuracy; point-of-care testing; sensitivity and specificity; whole capillary blood.

Fig 1

Distribution of participants by comparison. As shown in the left panel, 112 individuals provided both venous (left middle box) and capillary (right middle box) samples. The capillary samples were obtained using the Tasso-SST self-sampling device (Tasso, Inc., Seattle, USA) from all 112 participants, of which 86 also provided additional capillary samples via finger pricking. The co-primary objectives compared IgG (and IgG/IgM) from the NADAL venous serum and whole capillary samples to DiaSorin venous serum (lower middle box). Secondary objectives included comparisons of (I) DiaSorin on venous serum vs DiaSorin on serum capillary blood; (ii) NADAL on whole venous blood vs DiaSorin on venous serum; (iii) NADAL on whole capillary blood vs DiaSorin on serum capillary blood; (iv) NADAL on venous serum vs NADAL on whole capillary blood; (V) NADAL on venous serum vs NADAL on whole venous blood; and (vi) NADAL on capillary serum vs NADAL on whole capillary blood. Dashed lines in the schematic represent the test conditions, while solid lines indicate the reference conditions.

Fig 2

Distribution of DiaSorin IgG levels in venous serum by Nadal IgG test result on venous serum and whole capillary blood. Both panels display two violin plots representing the distribution of the log-transformed DiaSorin IgG levels (AU/mL) in venous serum (y-axis), according to the NADAL IgG test results (positive or negative) on the x-axis, when analyzed in venous serum (left panel) and the whole capillary blood (right panel). Violin plots depict the geometric mean (red dot) distribution of IgG levels with individual data points overlaid and the range (black error bars). Each violin represents the density of DiaSorin values within each NADAL result group, where the width reflects the concentration of data points at specific antibody levels. Wider regions of the violins indicate a higher frequency of values at that level. Horizontal dotted lines indicate the 15 AU/mL DiaSorin threshold for seropositivity.