Clinical and experimental factors that affect the reported performance characteristics of rapid testing for SARS-CoV-2

Pârvu,; Gary, Devin S.; Mann, J. John; Yang, Lin; Mills, Dorsey; Cooper, Lauren; Jc, Andrews; Manabe, Yukari C.; Pekosz, Andrew; Ck, Cooper

doi:10.1101/2021.05.20.21257181

Cited by 2 publications

(7 citation statements)

References 110 publications

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“…Therefore, these findings regarding the variability in RAT sensitivity, when stratified by the presence or absence of COVID-19 symptoms, are not surprising given that symptomatic individuals are typically associated with specimens that have a higher viral load. The results here are consistent with previous studies that have shown better sensitivity of SARS-CoV-2 RATs when specimens are obtained from symptomatic individuals ( 16 , 18 ). However, although RAT sensitivity is somewhat reduced when compared to molecular-based testing, several drawbacks are associated with molecular testing including limitations in specimen processing capacity ( 33 , 34 ), prolonged turnaround time (at best 24 hours when sample shipment is considered), and the need for dedicated staff and automated platforms; all of which can limit turnaround time and impede optimized patient management ( 35 ).…”

Section: Discussionsupporting

confidence: 92%

“…Although reflex RT-PCR testing was not performed for every RAT result, the reflex RT-PCR test results that were obtained showed a high percent (93.1%) agreement with RAT results from the total population. Overall, the results here are consistent with the general performance characteristics of SARS-CoV-2 RATs that have been demonstrated previously ( 16 , 18 ). Depending on the assumption for reflex RT-PCR testing that was applied, the sensitivity value for the RAT was either 77.2% (Assumption 1) or 85.6% (Assumption 2) in the symptomatic population, which overlaps with the sensitivity estimate [84% (95%CI: 67%, 93%)] listed for symptomatic individuals in Veritor's instructions for use ( 23 ).…”

Section: Discussionsupporting

confidence: 92%

“…Rapid antigen testing has a lower analytical sensitivity compared to nucleic acid amplification testing, which translates to a lower clinical sensitivity when compared to molecular testing-based reference assays ( 13 ). RAT sensitivity is significantly better when performed on upper respiratory specimens with a viral load between 1X10_5 and 1X10_6 genomic copies/mL (corresponding to a Ct score of ~ ≤30 and ≤25, respectively, depending on the reference RT-PCR assay employed) ( 18 , 27 – 32 ). Therefore, these findings regarding the variability in RAT sensitivity, when stratified by the presence or absence of COVID-19 symptoms, are not surprising given that symptomatic individuals are typically associated with specimens that have a higher viral load.…”

Section: Discussionmentioning

confidence: 99%

“…At relatively low viral loads, this could have affected “clinical truth,” and differentially led to RAT false-negative results in certain cases but true negative results in others. However, a meta-analysis that included over 80 RAT studies previously showed that the analytical sensitivity of the reference RT-PCR tests does not affect RAT performance in a statistically significant manner ( 18 ). In addition, the specimen collection procedure (e.g., nasal vs. nasopharyngeal swab) or the storage conditions (e.g., fresh vs. frozen) for reflex RT-PCR testing could have differed for individual RT-PCR tests in this data set, which could have impacted overall RAT agreement.…”

Section: Discussionmentioning

confidence: 99%

“…Recent work shows that performance values (e.g., test sensitivity and specificity) for individual SARS-CoV-2 RATs, reported from real-world studies, can differ when compared to those presented in the manufacturer's instructions for use (IFU) ( 13 – 18 ). Several factors, including study design and experimental bias, can affect RAT sensitivity estimates; ( 18 ) therefore, it is important to monitor their real-world performance ( 19 ). In addition, it is important to supplement registration studies with real-world studies to establish a precise performance profile for RATs over time.…”

Section: Introductionmentioning

confidence: 99%

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

Parikh

Cooper

Frogel

et al. 2022

Front. Public Health

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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.

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