Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence: Navigating the absence of a gold standard
Bibliographic record
Abstract
ABSTRACT Background Multiple anti-SARS-CoV-2 immunoassays are available, but no gold standard exists. We assessed four assays using various methodological approaches to estimate SARS-COV-2 seroprevalence during the first COVID-19 wave in Canada. Methods This serial cross-sectional study was conducted using plasma samples from healthy blood donors between April-September 2020. Qualitative assessment of SARS-CoV-2 IgG antibodies was based on four assays: Abbott Architect SARS-Cov-2 IgG assay (target nucleocapsid) (Abbott-NP) and three in-house IgG ELISA assays (target spike glycoprotein (Spike), spike receptor binding domain (RBD), and nucleocapsid (NP)). Seroprevalence was estimated using multiple composite reference standards (CRS) and by a series of Bayesian Latent Class Models (BLCM) (using uninformative, weakly, and informative priors). Results 8999 blood samples were tested. The Abbott-NP assay consistently estimated seroprevalence to be lower than the ELISA-based assays. Discordance between assays was common, 13 unique diagnostic phenotypes were observed. Only 32 samples (0.4%) were positive by all four assays. BLCM using uninformative priors predicted seroprevalence increased from 0.7% (95% credible interval (CrI); 0.4, 1.0%) in April/May to 0.8% (95% CrI 0.5, 1.2%) in June/July to 1.1% (95% CrI 0.7, 1.6) in August/September. Results from CRS were very similar to the BLCM. Assay characteristics varied considerably over time. Overall spike had the highest sensitivity (89.1% (95% CrI 79.2, 96.9%), while the sensitivity of the Abbott-NP assay waned from 65.3% (95% CrI 43.6, 85.0%) in April/May to 45.9% (95% CrI 27.8, 65.6) by August/September. Discussion We found low SARS-CoV-2 seroprevalence rates at the end of the first wave and estimates derived from single assays may be biased. Summary Multiple anti-SARS-CoV-2 immunoassays are available, but no gold standard exists. We used four unique assays to estimate very low SARS-COV-2 seroprevalence during the first COVID-19 wave in Canada. Caution should be exercised when interpretating seroprevalence estimates from single assays.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.166 | 0.182 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.002 |
| Science and technology studies | 0.001 | 0.005 |
| Scholarly communication | 0.004 | 0.002 |
| Open science | 0.003 | 0.003 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".