Assessing Vulnerability to COVID-19 in High-Risk Populations: The Role of SARS-CoV-2 Spike-Targeted Serology.

Individuals at increased risk for severe coronavirus disease-2019 (COVID-19) outcomes, due to compromised immunity or other risk factors, would benefit from objective measures of vulnerability to infection based on vaccination or prior infection. The authors reviewed published data to identify a specific role and interpretation of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike-targeted serology testing. Specific recommendations are provided for an evidence-based and clinically-useful interpretation of SARS-CoV-2 spike-targeted serology to identify vulnerability to infection and potential subsequent adverse outcomes. Decreased vaccine effectiveness among immunocompromised individuals is linked to correspondingly high rates of breakthrough infections. Negative results on SARS-CoV-2 antibody tests are associated with increased risk for subsequent infection. "Low-positive" results on semiquantitative SARS-CoV-2 spike-targeted antibody tests may help identify persons at increased risk as well. Standardized SARS-CoV-2 spike-targeted antibody tests may provide objective information on the risk of SARS-CoV-2 infection and associated adverse outcomes. This holds especially for high-risk populations that demonstrate a relatively high 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.

Performance evaluation of the Roche Elecsys Anti-SARS-CoV-2 S immunoassay.

The Elecsys® Anti-SARS-CoV-2 S immunoassay (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) has been developed for the detection of antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein. We evaluated the assay performance using samples from seven sites in Germany, Austria, and Switzerland. For specificity and sensitivity analyses, 7880 presumed negative pre-pandemic samples and 827 SARS-CoV-2 PCR-confirmed single or sequential samples from 272 different patients were tested, respectively. The overall specificity and sensitivity (≥14 days post-PCR) for the Elecsys Anti-SARS-CoV-2 S immunoassay were 99.95% (95% confidence interval [CI]: 99.87-99.99; 7876/7880) and 97.92% (95% CI: 95.21-99.32; 235/240), respectively. The Elecsys Anti-SARS-CoV-2 S immunoassay had significantly higher specificity compared with the LIAISON® SARS-CoV-2 S1/S2 IgG (99.95% [2032/2033] vs 98.82% [2009/2033]), ADVIA Centaur® SARS-CoV-2 Total (100% [928/928] vs 86.96% [807/928]), ARCHITECT SARS-CoV-2 IgG (99.97% [2931/2932] vs 99.69% [2923/2932]), iFlash-SARS-CoV-2 IgM (100.00% [928/928] vs 99.57% [924/928]), and EUROIMMUN Anti-SARS-CoV-2 IgG (100.00% [903/903] vs 97.45% [880/903]) and IgA (100.00% [895/895] vs 95.75% [857/895]) assays. The Elecsys Anti-SARS-CoV-2 S immunoassay had significantly higher sensitivity (≥14 days post-PCR) compared with the ARCHITECT SARS-CoV-2 IgG (98.70% [76/77] vs 87.01% [67/77]), iFlash-SARS-CoV-2 IgG (100.00% [76/76] vs 93.42% [71/76]) and IgM (100.00% [76/76] vs 35.53% [27/76]), and EUROIMMUN Anti-SARS-CoV-2 IgG (98.26% [113/115] vs 93.91% [108/115]) assays. Therefore, the Elecsys Anti-SARS-CoV-2 S assay demonstrated a reliable performance across various sample populations for the detection of anti-S antibodies.

Multicentre Performance Evaluation of the Elecsys Anti-SARS-CoV-2 Immunoassay as an Aid in Determining Previous Exposure to SARS-CoV-2.

INTRODUCTION: We performed a multicentre evaluation of the Elecsys® Anti-SARS-CoV-2 immunoassay (Roche Diagnostics), an assay utilising a recombinant protein representing the nucleocapsid (N) antigen, for the in vitro qualitative detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Specificity was evaluated using serum/plasma samples from blood donors and routine diagnostic specimens collected before September 2019 (i.e., presumed negative for SARS-CoV-2-specific antibodies); sensitivity was evaluated using samples from patients with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection. Point estimates and 95% confidence intervals (CIs) were calculated. Method comparison was performed versus commercially available assays. RESULTS: Overall specificity for the Elecsys Anti-SARS-CoV-2 immunoassay (n = 9575) was 99.85% (95% CI 99.75-99.92): blood donors (n = 6714; 99.82%), routine diagnostic specimens (n = 2861; 99.93%), pregnant women (n = 2256; 99.91%), paediatric samples (n = 205; 100.00%). The Elecsys Anti-SARS-CoV-2 immunoassay demonstrated significantly higher specificity versus LIAISON SARS-CoV-2 S1/S2 IgG (99.71% vs. 98.48%), EUROIMMUN Anti-SARS-CoV-2 IgG (100.00% vs. 94.87%), ADVIA Centaur SARS-CoV-2 Total (100.00% vs. 87.32%) and iFlash SARS-CoV-2 IgM (100.00% vs. 99.58%) assays, and comparable specificity to ARCHITECT SARS-CoV-2 IgG (99.75% vs. 99.65%) and iFlash SARS-CoV-2 IgG (100.00% vs. 100.00%) assays. Overall sensitivity for Elecsys Anti-SARS-CoV-2 immunoassay samples drawn at least 14 days post-PCR confirmation (n = 219) was 93.61% (95% CI 89.51-96.46). No statistically significant differences in sensitivity were observed between the Elecsys Anti-SARS-CoV-2 immunoassay versus EUROIMMUN Anti-SARS-CoV-2 IgG (90.32% vs. 95.16%) and ARCHITECT SARS-CoV-2 IgG (84.81% vs. 87.34%) assays. The Elecsys Anti-SARS-CoV-2 immunoassay showed significantly lower sensitivity versus ADVIA Centaur SARS-CoV-2 Total (85.19% vs. 95.06%) and iFlash SARS-CoV-2 IgG (86.25% vs. 93.75%) assays, but significantly higher sensitivity versus the iFlash SARS-CoV-2 IgM assay (86.25% vs. 33.75%). CONCLUSION: The Elecsys Anti-SARS-CoV-2 immunoassay demonstrated very high specificity and high sensitivity in samples collected at least 14 days post-PCR confirmation of SARS-CoV-2 infection, supporting its use to aid in determination of previous exposure to SARS-CoV-2.