Aerosol formation during processing of potentially infectious samples on Roche immunochemistry analyzers (cobas e analyzers) and in an end-to-end laboratory workflow to model SARS-CoV-2 infection risk for laboratory operators.

Objectives: To assess aerosol formation during processing of model samples in a simulated real-world laboratory setting, then apply these findings to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to assess the risk of infection to laboratory operators. Design: This study assessed aerosol formation when using cobas e analyzers only and in an end-to-end laboratory workflow. Recombinant hepatitis B surface antigen (HBsAg) was used as a surrogate marker for infectious SARS-CoV-2 viral particles. Using the HBsAg model, air sampling was performed at different positions around the cobas e analyzers and in four scenarios reflecting critical handling and/or transport locations in an end-to-end laboratory workflow. Aerosol formation of HBsAg was quantified using the Elecsys® HBsAg II quant II immunoassay. The model was then applied to SARS-CoV-2. Results: Following application to SARS-CoV-2, mean HBsAg uptake/hour was 1.9 viral particles across the cobas e analyzers and 0.87 viral particles across all tested scenarios in an end-to-end laboratory workflow, corresponding to a maximum inhalation rate of <16 viral particles during an 8-hour shift. Conclusion: Low production of marker-containing aerosol when using cobas e analyzers and in an end-to-end laboratory workflow is consistent with a remote risk of laboratory-acquired SARS-CoV-2 infection for laboratory operators.

Development and Validation of the Elecsys Anti-SARS-CoV-2 Immunoassay as a Highly Specific Tool for Determining Past Exposure to SARS-CoV-2.

The Elecsys Anti-SARS-CoV-2 immunoassay (Roche Diagnostics) was developed to provide accurate, reliable detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated sensitivity, specificity, cross-reactivity, and agreement with a vesicular stomatitis virus-based pseudoneutralization assay for the Elecsys Anti-SARS-CoV-2 immunoassay. Sensitivity and agreement between Elecsys Anti-SARS-CoV-2 immunoassay and pseudoneutralization assay measurements were evaluated using samples from patients with PCR-confirmed SARS-CoV-2 infection, a majority of whom were hospitalized. Specificity was evaluated using samples from routine diagnostic testing/blood donors collected before December 2019 and thus deemed negative for SARS-CoV-2-specific antibodies. Cross-reactivity was evaluated using samples containing a wide range of potentially cross-reacting analytes, purchased from commercial vendors. For sensitivity and specificity, point estimates and 95% confidence intervals (CIs) were calculated. Agreement between the Elecsys Anti-SARS-CoV-2 immunoassay and the pseudoneutralization assay was calculated. The sensitivity of the Elecsys Anti-SARS-CoV-2 immunoassay in patients with prior PCR-confirmed SARS-CoV-2 infection was 99.5% (95% CI, 97.0 to 100.0%) at ≥14 days post-PCR confirmation. Overall specificity (n = 10,453) was 99.80% (95% CI, 99.69 to 99.88%). Only 4/792 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 to 99.9%). Positive, negative, and overall agreement (n = 46) between the Elecsys Anti-SARS-CoV-2 immunoassay and the pseudoneutralization assay were 86.4% (95% CI, 73.3 to 93.6%), 100% (95% CI, 34.2 to 100%), and 87.0% (95% CI, 74.3 to 93.9%), respectively. The Elecsys Anti-SARS-CoV-2 immunoassay demonstrated high sensitivity (99.5% at ≥14 days post-PCR confirmation) and specificity (99.80%), supporting its use as a tool for identification of past SARS-CoV-2 infection, including use in populations with low disease prevalence.

Approaches to measurement of vitamin D concentrations - immunoassays.

The clinical relevance of vitamin D calls for analytically reliable and cost-effective testing methods. 25-hydroxyvitamin D (25(OH)D), the storage form of vitamin D in the blood circulation, is widely accepted as the best indicator of the individual vitamin D status. 25(OH)D immunoassays play a major role in routine testing in the clinical laboratory and many new automated immunoassays have been introduced to the market by the diagnostic industry in recent years. Detectability, precision, traceability and comparability to the reference method liquid chromatography - tandem mass spectroscopy (LCTMS) are essential quality requirements for 25(OH)D immunoassays. The hydrophobic nature of the analyte, the high concentration and affinity of vitamin D binding protein (VDBP) in serum and the cross-reactivity requirements due to the broad spectrum of metabolites of vitamin D are most demanding for assay development. It requires an adequate assay design including a thorough pretreatment process to inactivate the VDBP, careful selection of the specifier (antibody or binding protein) to meet the cross-reactivity requirement, and standardization of the assay versus LCTMS to achieve comparability of results between methods.