On 11 March 2020, the World Health Organization (WHO) declared the novel coronavirus (SARS-CoV-2) outbreak a global pandemic.¹ Currently, no specific therapy has proved to be effective against the infection. With the approval by WHO² of the first vaccine for emergency use against SARS-CoV-2 on 31 December 2020, it is important to understand the strength and duration of immunity after administration, which is induced by neutralizing anti-SARS-CoV-2 antibodies (nAbs).³ The same antibodies are also present in individuals once the SARS-CoV-2 infection is resolved, at levels that depend on the duration and severity of clinical symptoms.⁴ The efficacy of passive antibody therapy has been associated with the concentration of nAbs in the convalescent plasma (CP) of recovered patients.^{5, 6} Thus, it would be useful to immediately identify donors with high nAbs titres. The gold-standard test used to detect nAbs is the plaque reduction neutralization test (PRNT).⁷ However, neutralization assays are time- and cost-consuming, as well as being limited in availability, since they require biosafety level 3 laboratories with qualified staff.⁸ Several manufacturers have developed immunoassays compatible with global laboratory infrastructures for the COVID-19 emergency, enabling widespread testing of hundreds to thousands of samples per day. Recently, commercial SARS-CoV-2 antibody immunoassays have focused on the receptor-binding domain (RBD) of the spike protein (S),^{9, 10} which appears to be the main antigen responsible for eliciting neutralizing antibodies.^{5, 9, 11, 12} We aimed to investigate the correlation between nAbs titres identified by PRNT and the Maglumi 2019-nCoV IgG assay (Snibe, Shenzhen, China) with spike protein– and nucleocapsid (N)-based target, the Elecsys Anti-SARS-CoV-2 S assay (Roche, Basel, Switzerland) and the Maglumi SARS-CoV-2 S-RBD IgG assay, both of which target the spike protein RBD. Residual serum samples from 118 potential candidates for COVID-19 CP donation, with a confirmed negative PCR for COVID-19, were collected. The samples had been tested previously by PRNT, with the following distribution of titres: 1:20 in 3.4% of samples, 1:40 in 29.7%, 1:80 in 20.3%, 1:160 in 17.8% and 1:320 in 28.8%. The immunoassay signal values ranged from 0.45 to 2294.00 U/mL (median = 146.00 U/mL, IQR = 48.00-389.00 U/mL), from 2.10 to 791.70 AU/mL (median = 35.92 AU/mL, IQR = 21.82-92.52 AU/mL) and from 0.01 to 40.13 AU/mL (median = 4.07 AU/mL, IQR = 1.33-6.82 AU/mL) for the Elecsys Anti-SARS-CoV-2 S, Maglumi SARS-CoV-2 S-RBD IgG and Maglumi 2019-nCoV IgG assays, respectively. The overall difference in median serological test values among the titre groups was statistically significant. The reported data are shown in Figure 1. Using the predefined assay thresholds to establish whether the test results are positive or negative (0.8 U/mL for Elecsys Anti-SARS-CoV-2 S, 1 AU/mL for both Maglumi SARS-CoV-2 S-RBD IgG and Maglumi 2019-nCoV IgG assays), 21.37% of samples were below the threshold for the S/N IgG assay but were reactive for the RBD Ig assays. The simple linear regression analysis performed on the transformed data showed that there is a stronger positive association between serological test values and the PRNT for the Roche assay (R² = 0.566, P < .0001) than for the Maglumi RBD IgG (R² = 0.372, P <.0001) and the Maglumi S/N IgG assays (R² = 0.149, P < .0001). Moreover, the Spearman test confirmed a strong positive linear relationship between RBD Ig antibodies and neutralization titres: rs = 0.767; P < .0001 for the Roche total RBD Ig assay; and rs = 0.643; P < .0001 for the Maglumi RBD IgG assay, whereas the magnitude of the correlation between the assay targeting S-binding IgG antibodies (Maglumi S/N IgG) and neutralization activity is weaker: rs = 0.395, P < .0001 (Figure 2). Owing to the difficulty finding CP donors with a neutralizing titre of at least 1:160 for human passive immunization studies, a titre of 1:80 was considered to be acceptable if an alternative matched unit is not available. For this reason, we evaluated the performance of the immunoassays to detect nAbs titres ≥1:80 through receiver operating characteristic (ROC) curves (Figure 3): the area under the curve (AUC) for the Roche assay (AUC = 0.973) was greater than for the other two assays (AUC = 0.917 for Maglumi RBD IgG and AUC = 0.796 for Maglumi S/N IgG). We selected optimal cut-offs as predictors, using the maximum value of the Youden index, which maximizes the sum of sensitivity and specificity, as shown in Table 1. Compared with other studies, which show that anti-S IgG antibody titres correlate with the plaque reduction neutralization test,^13-15 we observed that the Roche total RBD Ig assay showed the best correlation and performance for identifying nAbs titres ≥1:80, which is consistent with the fact that the RBD antigen is a key target for these antibodies.^{5, 9, 11, 12} In conclusion, we characterized the performance of three commercially available anti-SARS-CoV-2 Ig immunoassays. In particular, anti-RBD Ig assays could serve as useful surrogates for nAbs testing, as they are suitable for identifying highly neutralizing plasma samples with low biosafety requirements compared with other methods. These assays are also promising public health tools for monitoring seroconversion in the post-vaccinated population, since they can perform fast and high-throughput tests while keeping up the vaccination rate.