ABSTRACT
ImportanceIndividuals at increased risk for severe outcomes from COVID-19, due to compromised immunity or other risk factors, would benefit from objective measures of vulnerability to infection based on prior infection and/or vaccination. We reviewed published data to identify a specific role and interpretation of SARS-CoV-2 spike-targeted serology testing for such individuals. We also provide real-world evidence of spike-targeted antibody test results, identifying the seronegativity rate across the United States from March 2021 through June 2022. Analysis of antibody test results were compared between post-transplant (ie, immunocompromised) and all other patients tested in the first half of 2022. Finally, specific recommendations are provided for an evidence-based and clinically useful interpretation of spike-targeted serology to identify vulnerability to infection and potential subsequent adverse outcomes. ObservationsDecreased vaccine effectiveness among immunocompromised individuals is linked to correspondingly high rates of breakthrough infections. Evidence indicates that negative results on SARS-CoV-2 antibody tests are associated with increased risk for subsequent infection. Results from widely available, laboratory-based tests do not provide a direct measure of protection but appear to correlate well with the presence of surrogate pseudovirus-neutralizing antibodies. The results of SARS-CoV-2 semiquantitative tests have also been associated with vaccine effectiveness and the likelihood of breakthrough infection. The data suggest that "low-positive" results on semiquantitative SARS-CoV-2 spike-targeted antibody tests may help identify persons at increased relative risk for breakthrough infection leading to adverse outcomes. In an analysis of data from large national laboratories during the COVID-19 Omicron-related surge in 2022, results from SARS-CoV-2 spike-targeted antibody tests were negative in 16.6% (742/4459) of solid organ transplant recipients tested compared to only 11.0% (47,552/432,481) of the remaining tested population. Conclusions and RelevanceStandardized semiquantitative and quantitative SARS-CoV-2 spike-targeted antibody tests may provide objective information on risk of SARS-CoV-2 infection and associated adverse outcomes. This holds especially for high-risk populations, including transplant recipients, who demonstrate a relatively higher rate of seronegativity. The widespread availability of such tests presents an opportunity to refine risk assessment for individuals with suboptimal SARS-CoV-2 antibody levels and to promote effective interventions. Interim federal guidance would support physicians and patients while additional investigations are pursued.
ABSTRACT
BackgroundThe Elecsys(R) Anti-SARS-CoV-2 S immunoassay (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) has been developed for the in vitro quantitative detection of antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein. We evaluated the performance of this assay using samples from seven sites in Germany, Austria, and Switzerland. MethodsAnonymized frozen, residual serum, or plasma samples from blood donation centers or routine diagnostic testing were used for this study. For specificity and sensitivity analyses, presumed negative samples collected before October 2019 and SARS-CoV-2 PCR-confirmed single or sequential samples were tested, respectively. The performance of the Elecsys Anti-SARS-CoV-2 S immunoassay was also compared with other commercial immunoassays. ResultsThe overall specificity (n=7880 pre-pandemic samples) and sensitivity (n=240 PCR-positive samples [[≥]14 days post-PCR]) for the Elecsys Anti-SARS-CoV-2 S immunoassay were 99.95% (95% confidence interval [CI]: 99.87-99.99) and 97.92% (95% CI: 95.21- 99.32), respectively. Compared with seven other immunoassays, the Elecsys Anti-SARS-CoV-2 S assay had comparable or greater specificity and sensitivity. The Elecsys Anti-SARS-CoV-2 S immunoassay had significantly higher specificity compared with the LIAISON(R) SARS-CoV-2 S1/S2 IgG, ADVIA Centaur(R) SARS-CoV-2 Total, ARCHITECT SARS-CoV-2 IgG, iFlash-SARS-CoV-2 IgM, and EUROIMMUN Anti-SARS-CoV-2 IgG and IgA assays, and significantly higher sensitivity ([≥]14 days post-PCR) compared with the ARCHITECT SARS-CoV-2 IgG, iFlash-SARS-CoV-2 IgG and IgM, and EUROIMMUN Anti-SARS-CoV-2 IgG assays. ConclusionThe Elecsys Anti-SARS-CoV-2 S assay demonstrated a robust and favorable performance across samples from multiple European sites, with a very high specificity and sensitivity for the detection of anti-S antibodies.
ABSTRACT
BackgroundThe Elecsys(R) Anti-SARS-CoV-2 electrochemiluminescence immunoassay (Roche Diagnostics International Ltd) was developed for the in vitro qualitative detection of antibodies to SARS-CoV-2. We evaluated the sensitivity of the Elecsys Anti-SARS-CoV-2 immunoassay in samples from a diverse cross-section of patients across multiple sites and compared results against commercially available comparators. MethodsSensitivity of the Elecsys Anti-SARS-CoV-2 immunoassay was evaluated using anonymised, frozen, residual single and sequential serum and plasma samples from patients with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection. Point estimates and 95% confidence intervals (CIs) were calculated and method comparisons performed versus the following comparator assays: Euroimmun Anti-SARS-CoV-2 IgG, Abbott ARCHITECT SARS-CoV-2 IgG, Siemens ADVIA Centaur SARS-CoV-2 Total, and YHLO iFlash SARS-CoV-2 IgG and IgM. ResultsOverall sensitivity for the Elecsys Anti-SARS-CoV-2 immunoassay in 219 samples drawn [≥]14 days post-PCR confirmation was 93.6% (95% CI 89.5-96.5). Across the three study sites, sensitivity in samples drawn [≥]14 days post-PCR confirmation ranged from 85.7-98.9%. Sensitivity was significantly higher for the Elecsys Anti-SARS-CoV-2 immunoassay compared with the YHLO iFlash SARS-CoV-2 IgM assay for samples drawn [≥]14 days post-PCR confirmation (86.3% [95% CI 76.7-92.9] versus 33.8% [95% CI 23.6-45.2]). Both Siemens ADVIA Centaur SARS-CoV-2 Total and YHLO iFlash SARS-CoV-2 IgG assays had a significantly higher sensitivity compared with the Elecsys Anti-SARS-CoV-2 immunoassay for samples drawn [≥]14 days post-PCR confirmation (95.1% [95% CI 87.8-98.6] versus 85.2% [95% CI 75.6-92.1]; 93.8% [95% CI 86.0-97.9] versus 86.3% [95% CI 76.7-92.9]). Differences in sensitivity between the Elecsys Anti-SARS-CoV-2 immunoassay and the Euroimmun Anti-SARS-CoV-2 IgG (90.3% [95% CI 83.7-94.9] versus 95.2% [95% CI 89.8-98.2]) and Abbott ARCHITECT SARS-CoV-2 IgG (84.8% [95% CI 75.0-91.9] versus 87.3% [95% CI 78.0-93.8]) assays for samples drawn [≥]14 days post-PCR confirmation were not significant. ConclusionsThe Elecsys Anti-SARS-CoV-2 immunoassay demonstrated high sensitivity in samples collected [≥]14 days post-PCR confirmation of SARS-CoV-2 infection, and comparable sensitivity to several commercially available comparator assays across multiple sites, supporting the use of this assay as a tool to aid in determination of previous exposure to SARS-CoV-2. Required information for submission systemO_ST_ABSEthical guidelinesC_ST_ABSThe study was conducted in accordance with the study protocol provided by Roche Diagnostics and in accordance with the principles of the Declaration of Helsinki. All human samples utilised at the three study sites in Germany (Augsburg, Heidelberg, Berlin) were anonymised, frozen, residual samples, therefore no ethical approval or waiver was required in accordance with local legislation from ZEKO (Central Ethics Commission at the German Medical Association). A statement was obtained from the Ethics Committee of the Landesarztekammer Bayern confirming that there are no objections to the coherent use of anonymised residual samples. Research reporting guidelinesPlease see separate STARD checklist. Data availability statementQualified researchers may request access to individual patient level data through the clinical study data request platform (https://vivli.org/). Further details on Roches criteria for eligible studies are available here: https://vivli.org/members/ourmembers/. For further details on Roches 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
