Development and validation of the Elecsys Anti-SARS-CoV-2 immunoassay as a highly specific tool for determining past exposure to SARS-CoV-2

AbstractBackgroundThe Elecsys® Anti-SARS-CoV-2 immunoassay (Roche Diagnostics) was developed to provide an accurate and reliable method for the detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the sensitivity, specificity, and cross-reactivity of the Elecsys Anti-SARS-CoV-2 immunoassay.MethodsThe performance of the Elecsys Anti-SARS-CoV-2 immunoassay was assessed at Roche Diagnostics (Penzberg, Germany). Sensitivity was evaluated using anonymised residual frozen samples from patients who had previously tested positive for SARS-CoV-2 infection by polymerase chain reaction (PCR); one or more consecutive samples were collected from patients at various timepoints after PCR confirmation. Specificity was evaluated using anonymised unselected residual frozen samples from routine diagnostic testing or from blood donors; all samples were collected before December 2019 and thus deemed negative for SARS-CoV-2-specific antibodies. Cross-reactivity was evaluated using anonymised frozen samples containing a wide range of potentially cross-reacting analytes, which were purchased from commercial vendors. For sensitivity and specificity, point estimates and 95% confidence intervals (CIs) were calculated.ResultsSensitivity of the Elecsys Anti-SARS-CoV-2 immunoassay in 496 samples from 102 patients with prior PCR-confirmed SARS-CoV-2 infection was 99.5% (95% CI 97.0–100.0) at ≥14 days after PCR confirmation. Overall specificity in 10,453 samples from routine diagnostic testing (n = 6305) and blood donors (n = 4148) was 99.80% (95% CI 99.69–99.88). Only 4/752 samples containing potential cross-reacting analytes were reactive with the Elecsys Anti-SARS-CoV-2 immunoassay, resulting in an overall specificity in this cohort of 99.5% (95% CI 98.6–99.9).ConclusionThe Elecsys Anti-SARS-CoV-2 immunoassay demonstrated a sensitivity of 99.5% at ≥14 days after PCR confirmation and a very high specificity of 99.80%. Our findings support the use of the Elecsys Anti-SARS-CoV-2 immunoassay as a tool for the identification of past SARS-CoV-2 infection, including in populations with a low disease prevalence.Required information for submission systemEthical guidelinesThe study was conducted in accordance with applicable regulations, including relevant European Union directives and regulations, and the principles of the Declaration of Helsinki. All samples, excluding the specimens that were provided by commercial sample vendors, were transferred to Roche following anonymisation. For studies with anonymised leftover specimens, no ethics committee vote is required. A statement was obtained from the Ethics Committee of the Landesä rztekammer Bayern confirming that there are no objections against the transfer and the coherent use of the anonymised leftover samples.Research reporting guidelinesPlease see separate STARD checklistData availability statementQualified researchers may request access to individual patient level data through the clinical study data request platform (https://vivli.org/). Further details on Roche’s criteria for eligible studies are available here: https://vivli.org/members/ourmembers/. For further details on Roche’s Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here: https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm.