Large-Scale SARS-CoV-2 Antigen Testing With Real-World Specimens

Abstract

Real-world data are needed to establish SARS-CoV-2 rapid antigen testing (RAT) as an effective and reliable approach for SARS-CoV-2 screening. This study included 1,952,931 individuals who provided upper respiratory specimens during SARS-CoV-2 screening at CityMD urgent care locations in the New York metropolitan area from October 2020 to March 2021. Positive and negative results, as determined by the BD Veritor™ System for Rapid Detection of SARS-CoV-2 antigen (Veritor), were obtained for all individuals, with reflex reverse transcriptase-polymerase chain reaction (RT-PCR) testing performed on a case-by-case basis, per standard of care. Using verification bias adjustment, two alternative model assumptions were utilized for RAT results with missing reflex RT-PCR results. The worst antigen diagnostic performance estimates asserted that missing RT-PCR results would show a distribution similar to those RT-PCR results actually obtained, based on symptom category. The best antigen diagnostic performance estimates asserted that individuals without RT-PCR results had a clinical presentation consistent with RAT results, and, therefore, missing RT-PCR results would agree with RAT results. For patients with symptoms or high-risk exposure, 25.3% (n = 86,811/343,253) of RAT results were positive; vs. 3.4% (n = 53,046/1,559,733) positive for asymptomatic individuals without high-risk exposure. Reflex RT-PCR results were obtained from 46.3% (n = 158,836/343,253) and 13.8% (n = 215,708/1,559,733) of symptomatic and asymptomatic individuals, respectively. RT-PCR confirmed 94.4% (4,265/4,518) of positive and 90.6% (139,759/154,318) of negative RAT results in symptomatic individuals; and confirmed 83.4% (6,693/8,024) of positive and 95.3% (197,955/207,684) of negative RAT results in asymptomatic individuals. Applied assumptions for missing reflex RT-PCR results led to worst performance sensitivity estimates of 77.2 and 38.5% in the symptomatic and asymptomatic populations, respectively; assumptions for best performance estimates led to sensitivity values of 85.6 and 84.2%, respectively. Specificity values, regardless of assumptions or symptom category, ranged from 97.9–99.9%. At 10% SARS-CoV-2 prevalence, RAT positive predictive value was 86.9 and 99.0% for worst and best performance estimates across the total population, respectively; negative predictive values were >95% regardless of the applied assumption. Veritor test performance was consistent with that listed in the manufacturer instructions for use for symptomatic individuals. Real-world evidence should be gathered on RATs to support their efficacy as SARS-CoV-2 persists.

Effectiveness of Covid-19 vaccines against symptomatic and asymptomatic SARS-CoV-2 infections in an urgent care setting

“…Because the study participants are restricted to those who attend an urgent care clinic for a test, the test-negative study design can potentially control for selection bias arising due to differences in healthcare-seeking behavior between cases and controls. Use of highly specific and sensitive molecular tests and highly specific rapid antigen tests for case detection makes outcome misclassification less likely [19] , [23] . This design has been popular for estimating COVID-19 vaccine effectiveness [24] , [25] , [26] .…”

Development, testing and validation of a SARS-CoV-2 multiplex panel for detection of the five major variants of concern on a portable PCR platform

“…Unlike SGTF, in which negative results are used as a proxy to indicate presence of variants like Alpha and Omicron BA.1, this variant PCR panel comprises specific assays that detect only the mutant template and not the wild type, so variant detection is based on positive results rather than a lack of results. (6) During the course of the pandemic, multiple "discrete" waves of variants emerged. Hence, unique variant panels can be very useful to detect variants with no ambiguity when there are multiple variants in the community; the same is true for mixed infections (55).…”

“…The COVID-19 pandemic response has been complicated by the fact that as many as 40% of infected individuals may be asymptomatic depending on the population cohort, while secondary transmission might still be occurring ( 5 ). Hence, PCR tests remain the gold standard for SARS-CoV-2 detection because of their exquisite sensitivity and better performance identifying asymptomatic cases when compared to rapid antigen tests ( 6 ). It has been argued that PCR tests may show positivity for a longer duration—even after the individual is no longer infectious—and hence rapid antigen tests may be more reflective of infectivity ( 7 , 8 ).…”

Clinical practice of rapid antigen tests for SARS-CoV-2 Omicron variant: A single-center study in China

“…Several works outside of China have evaluated the performance of RATs in real-world situations ( Erman Daloğlu et al, 2022 ; Mane et al, 2022 ; Parikh et al, 2022 ; Schrom et al, 2022 ). However, what and how big a role RATs should play in China as part of its disease prevention policy are still unclear.…”