To assess the current coronavirus pandemic, there is a pressing need to determine the exposure and seroconversion to SARS-CoV-2 on a local and global level. Here, we demonstrate a sensitive and specific S-protein based assay that is well suited for detection of weak SARS- CoV-2-directed IgG responses, and that could identify exposed individuals with asymptomatic infection without the requirement of PCR diagnostics. Our results raise the possibility that on- going population-based studies using less sensitive state-of-the-art serological assays may significantly underestimate the frequency of exposure and seroconversion to SARS-CoV-2.

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We evaluated the performance of eleven SARS-CoV-2 antibody tests using a reference set of heat-inactivated samples from 278 unexposed persons and 258 COVID-19 patients, some of whom contributed serial samples. The reference set included samples with a variation in SARS-CoV-2 IgG antibody titers, as determined by an in-house immunofluorescence assay (IFA). The five evaluated rapid diagnostic tests had an IgG-based specificity of 99.0% and a sensitivity that ranged from 56.3–81.6% and decreased with low IFA titers. The specificity was > 99% for five out of six platform-based tests, and when assessed using samples collected ≥ 22 days after symptom onset, two assays had a sensitivity of > 96%. These two assays also detected samples with low IFA titers more frequently than the other assays. In conclusion, the evaluated antibody tests showed a heterogeneity in their performances and only a few tests performed well with samples having low IFA IgG titers, an important aspect for diagnostics and epidemiological investigations.