The Impact of Increasing Prevalence, False Omissions, and Diagnostic Uncertainty on Coronavirus Disease 2019 (COVID-19) Test Performance.

Kost, Gerald J

CONTEXT Coronavirus disease 2019 (COVID-19) test performance depends on predictive values in settings of increasing disease prevalence. Geospatially distributed diagnostics with minimal uncertainty facilitate efficient point-of-need strategies. OBJECTIVES To use original mathematics to interpret COVID-19 test metrics; assess Food and Drug Administration Emergency Use Authorizations and Health Canada targets; compare predictive values for multiplex, antigen, polymerase chain reaction kit, point-of-care antibody, and home tests; enhance test performance; and improve decision-making. DESIGN PubMed/newsprint generated articles documenting prevalence. Mathematica and open access software helped perform recursive calculations, graph multivariate relationships, and visualize performance by comparing predictive value geometric mean-squared patterns. RESULTS Tiered sensitivity/specificity comprise: T1) 90%, 95%; T2) 95%, 97.5%; and T3) 100%, ≥99%. Tier 1 false negatives exceed true negatives at >90.5% prevalence; false positives exceeded true positives at <5.3% prevalence. High sensitivity/specificity tests reduce false negatives and false positives yielding superior predictive values. Recursive testing improves predictive values. Visual logistics facilitate test comparisons. Antigen test quality falls off as prevalence increases. Multiplex severe acute respiratory syndrome (SARS)-CoV-2)*Influenza A/B*Respiratory-Syncytial Virus (RSV) testing performs reasonably well compared to Tier 3. Tier 3 performance with a Tier 2 confidence band lower limit will generate excellent performance and reliability. CONCLUSIONS The overriding principle is select the best combined performance and reliability pattern for the prevalence bracket. Some public health professionals recommend repetitive testing to compensate for low sensitivity. More logically, improved COVID-19 assays with less uncertainty conserve resources. Multiplex differentiation of COVID-19 from Influenza A/B-RSV represents an effective strategy if seasonal flu surges next year.