Head-to-Head Comparison of Two SARS-CoV-2 Serology Assays

Abstract

Background While molecular techniques remain the gold standard for diagnosis of acute SARS-CoV-2 infection, serological tests have the unique potential to ascertain how much of the population has been exposed to the COVID-19 pathogen. There have been limited published studies to date documenting the performance of SARS-CoV-2 antibody assays. Methods We compared the DiaSorin Liaison SARS-CoV-2 S1/S2 IgG and Roche Diagnostics Elecsys Anti-SARS-CoV-2 assays using 228 samples spanning patients with positive PCR for SARS-CoV-2, patients with compatible symptoms but negative PCR, pre-COVID specimens, and potential cross-reactives. Results Both assays detected antibodies in 18/19 samples collected at least one week after a positive PCR result. Neither method consistently detected antibodies in specimens collected within one week of a positive PCR result (sensitivity < 50%), but antibodies were detected by only Roche in four samples in this time frame. Using 139 pre-COVID and 35 PCR-negative samples, the Roche and DiaSorin assays demonstrated specificities of 100.0% and 98.9%, respectively. Neither assay demonstrated cross-reactivity from other coronaviruses (229E, HKU1, NL63, OC43), respiratory pathogens (adenovirus, metapneumovirus, rhinovirus/enterovirus), or antibodies to other viruses (HIV, EBV, CMV, HBV, HCV, HAV). Discussion Overall, the qualitative interpretations afforded by the Roche and DiaSorin assays agreed for 99% of samples evaluated. Minor discrepancies in sensitivity and specificity were observed between methods, with the differences in specificity more clinically significant for our low-prevalence population. For the DiaSorin assay, all disagreements with the Roche assay occurred in samples with quantitative signals near the cut-off determining positivity.

Comparative performance of five commercially available serologic assays to detect antibodies to SARS-CoV-2 and identify individuals with high neutralizing titers

“…This variability in assay performance should be considered when selecting an EIA to detect antibodies against SARS-CoV-2 and/or high nAbs among recovered persons.Consistent with our findings, there is growing evidence that both the Abbott and Roche assays have comparable performance characteristics that are often superior to many other commercially available ELISAs to detect IgG or total antibodies against SARS-CoV-2 in convalescent individuals 19,20. Although we did not include "challenge" specimens to examine potential crossreactivity of antibodies to other pathogens, others have shown limited evidence of crossreactivity for the Euroimmun, EDI, Roche, and Abbott assays 19,[21][22][23][24][25]. Data on the performance of the ImmunoDiagnostics ELISA to detect SARS-CoV-2 antibodies are limited.Large public health laboratories and large blood collection centers often rely on automated serological platforms-like those by Roche and Abbott-for screening of multiple pathogens including SARS-CoV-2.…”

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

“…In the two-test approach, the overall result was considered positive if the sample tested positive by both assays and negative if the sample was negative using one or both assays. When calculating the positive predictive value (PPV) or negative predictive value (NPV) at various prevalence rates, assay sensitivity was defined as the observed sensitivity using samples collected >14 days after symptom onset (when sensitivity is reported to be its highest) ( 8 – 10 ). Specificity was defined (for PPV and NPV calculations) as the value obtained when all control samples were combined.…”

“…Considering the relatively low prevalence of COVID-19 infection in many tested populations and the implications of false-positive results for patient care and public health measures, the Centers for Disease Control and Prevention (CDC) has determined that highly specific (≥99.5%) serologic tests are required to provide adequate positive predictive value (PPV) ( 7 ). Although high specificity is reported for many commercial SARS-CoV-2 serologic assays, not all of them consistently meet this specificity threshold (see Table S1 in the supplemental material) ( 8 – 10 ). A potential approach to ensure consistently high specificity involves the application of a two-test algorithm in which reactivity using one assay is confirmed using a different (orthogonal) assay.…”

SARS-CoV-2 Infection during Pregnancy in a Rural Midwest All-delivery Cohort and Associated Maternal and Neonatal Outcomes

“…Prior studies have shown that these assays become positive, at the earliest, 5 to 7 days after COVID-19 RT-PCR positivity and are nearly 100% positive by 3 weeks. 12,13 Deidentified existing plasma samples from 103 healthy individuals collected at least 1 year prior to the COVID-19 outbreak were tested as negative controls. Discrepancies between the DiaSorin and Roche assays were resolved using a third assay: the EUROIMMUN Anti-SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) IgG.…”