The Coronavirus Standards Working Group’s roadmap for improved population testing

Mercer, Tim R.; Almond, Neil; Crone, Michael; Chain, Patrick; Deshpande, Alina; Eveleigh, Deepa; Freemont, Paul S.; Fuchs, Sébastien; Garlick, Russell; Huggett, Jim F.; Kammel, Martin; Li, Po-E; Milavec, Mojca; Marlowe, Elizabeth M.; O’Sullivan, Denise M; Page, Mark; Pestano, Gary A.; Suliman, Sara; Simen, Birgitte B.; Sninsky, John J.; Sopchak, Lynne; Tato, Cristina M.; Vallone, Peter M.; Vandesompele, Jo; White, Thomas J.; Zeichhardt, Heinz; Salit, Marc

doi:10.1038/s41587-022-01538-1

Cited by 10 publications

(9 citation statements)

References 22 publications

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“…5,7,89 However, Ag-RDTs and some rapid molecular tests have lower analytical sensitivity than most gold-standard reverse-transcription quantitative PCR (RT-qPCR) tests and therefore require high viral loads (typically greater than 10 5 copies/mL) to reliably yield positive results. 7,8,[10][11][12][13][14][15][16][17][18] Further, Ag-RDTs are frequently used in unintended ways. 15,19 For example, although many Ag-RDTs are not authorized for asymptomatic use and/or have poor clinical sensitivity in asymptomatic populations [20][21][22][23] they are widely used for test-to-enter and serial-screening purposes.…”

Section: Introductionmentioning

confidence: 99%

“…7,8,[10][11][12][13][14][15][16][17][18] Further, Ag-RDTs are frequently used in unintended ways. 15,19 For example, although many Ag-RDTs are not authorized for asymptomatic use and/or have poor clinical sensitivity in asymptomatic populations [20][21][22][23] they are widely used for test-to-enter and serial-screening purposes. 14,21,24 One view of Ag-RDTs is that these tests (and molecular tests with low analytical sensitivity) can still prevent or mitigate SARS-CoV-2 outbreaks if they are used frequently.…”

Section: Introductionmentioning

confidence: 99%

“…Viralload timecourses from individuals in these studies show that for some individuals, several days can pass between when viral loads reach potentially infectious levels and when viral loads rise to the limits of detection (LODs) of Ag-RDTs (approximately 10 5 to 10 7 copies/mL). 7,8,[10][11][12][13][14][15][16][17]51,52 . During this window, previously conceptualized as a period of cryptic transmission, 59 false-negative Ag-RDT results may embolden social contact and increase transmission.…”

Section: Introductionmentioning

confidence: 99%

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Why Daily SARS-CoV-2 Nasal Rapid Antigen Testing Poorly Detects Infected and Infectious Individuals

Winnett

Akana

Shelby

et al. 2022

Preprint

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Background. To limit viral transmission, COVID-19 testing strategies must evolve as new SARS-CoV-2 variants (and new respiratory viruses) emerge to ensure that the specimen types and test analytical sensitivities being used will reliably detect individuals during the pre-infectious and infectious periods. Our accompanying work demonstrated that there are extreme differences in viral loads among paired saliva (SA), anterior-nares swab (ANS) and oropharyngeal swab (OPS) specimens collected from the same person and timepoint. We hypothesized that these extreme differences may prevent low-analytical-sensitivity assays (such as antigen rapid diagnostic tests, Ag-RDTs) performed on a single specimen type from reliably detecting pre-infectious and infectious individuals. Methods. We conducted a longitudinal COVID-19 household-transmission study in which 228 participants collected SA, ANS, and OPS specimens for viral-load quantification by RT-qPCR, and performed an ANS Ag-RDT (Quidel QuickVue At-Home OTC COVID-19 Test) daily. We evaluated the performance of the Ag-RDT (n=2215 tests) to detect infected individuals (positive results in any specimen type by RT-qPCR) and individuals with presumed infectious viral loads (at or above thresholds of 10^4, 10^5, 10^6, or 10^7 copies/mL). Results. Overall, the daily Ag-RDT detected 44% (358/811) timepoints from infected individuals. From 17 participants who enrolled early in the course of infection, we found that daily Ag-RDT performance was higher at timepoints when symptoms were reported, but symptoms only weakly correlated with SARS-CoV-2 viral loads, so ANS Ag-RDT clinical sensitivity remained below 50%. The three specimen types exhibited asynchronous presumably-infectious periods (regardless of the infectious viral-load threshold chosen) and the rise in ANS viral loads was delayed relative to SA or OPS for nearly all individuals, which resulted in the daily ANS Ag-RDT detecting only 3% in the pre-infectious period and 63% in the infectious period. We evaluated a computationally-contrived combined AN-OP swab based on viral loads from ANS and OPS specimens collected at the same timepoint; when tested with similar analytical sensitivity as the Ag-RDT, this combined swab was predicted to have significantly better performance, detecting up to 82% of infectious individuals. Conclusion. Daily ANS rapid antigen testing missed virtually all pre-infectious individuals, and more than one third of presumed infectious individuals due to low-analytical-sensitivity of the assay, a delayed rise in ANS viral loads, and asynchronous infectious viral loads in SA or OPS. When high-analytical-sensitivity assays are not available and low-analytical-sensitivity tests such as Ag-RDTs must be used for SARS-CoV-2 detection, an AN-OP combination swab is predicted to be most effective for detection of pre-infectious and infectious individuals. More generally, low-analytical-sensitivity tests are likely to perform more robustly using oral-nasal combination specimen types to detect new SASR-CoV-2 variants and emergent upper respiratory viruses.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Why Daily SARS-CoV-2 Nasal Rapid Antigen Testing Poorly Detects Infected and Infectious Individuals

Winnett

Akana

Shelby

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Because legal procedures for approval of assays and qualification of test facilities and their personnel were suspended during the pandemic, the reliability of test results became questionable, especially when reported differences in the performance of SARS-CoV-2 assays suggested considerable rates of false-negative and sometimes also false-positive results. 2 , 3 , 4 SARS-CoV-2 testing, therefore, does not necessarily mean obtaining reliable results. Although total counts of erroneous results will remain unknown, they could have affected epidemiological indicators.…”

mentioning

confidence: 99%

“…At times when official surveillance is suspended, such schemes are the only way to recognise the performance of testing facilities and test systems. EQA schemes have proven suitable with regard to the detection of pathogens by antigen 2 and nucleic acid amplification tests, 3 but also with regard to the effects of pooling of samples. 4 …”

mentioning

confidence: 99%