Evaluation of Three Commercial SARS-CoV-2 Serologic Assays and their Performance in Two-Test Algorithms.

Background. Sensitive and specific SARS-CoV-2 serologic assays are needed to inform diagnostic, therapeutic, and public health decision-making. We evaluated three commercial serologic assays as stand-alone tests and as components of two-test algorithms. Methods. Two nucleocapsid (Abbott IgG and Roche total antibody) and one spike-protein (DiaSorin IgG) antibody tests were included. We assessed sensitivity using 128 serum samples from symptomatic PCR-confirmed COVID-19-infected patients, and specificity using 1204 samples submitted for routine serologies prior to COVID-19's emergence, plus 64 pandemic-era samples from SARS-CoV-2 PCR-negative patients with respiratory symptoms. Assays were evaluated as stand-alone tests and as components of a two-test algorithm in which positive results obtained using one assay were verified using a second assay. Results. The two nucleocapsid antibody tests were more sensitive than the spike-protein antibody test overall (70% and 70% versus 57%; P≤0.003), with pronounced differences observed using samples collected 7-14 days after symptom onset. All three assays were comparably sensitive (≥89%, P≥0.13) using samples collected >14 days after symptom onset. Specificity was higher using the nucleocapsid antibody tests (99.3% and 99.7%) compared with the spike protein antibody test (97.8%, P≤0.002). When any two assays were paired in a two-test algorithm, specificity was 99.9% (P<0.0001 to 0.25 compared with the individual assays), and positive predictive value (PPV) improved substantially with minimal effect on negative predictive value (NPV). Conclusions. Two nucleocapsid antibody tests outperformed a spike protein antibody test. Pairing two different serologic tests in a two-test algorithm improves PPV compared with the individual assays alone, while maintaining NPV.