Sequencing SARS-CoV-2 from antigen tests

Nazario-Toole, Ashley E.; Nguyen, Holly M.; Xia, Hui; Frankel, Dianne N; Kieffer, John; Gibbons, Thomas F.

doi:10.1371/journal.pone.0263794

Cited by 16 publications

(12 citation statements)

References 15 publications

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“…Our work highlights the importance of also monitoring N antigen diversity, to assess how new mutations may limit the performance of antigen tests. Finally, it was recently shown that SARS-CoV-2 genome sequencing from antigen tests is possible 43 . If this were to become a widely used surveillance tool, our study suggests that sequencing positive and negative antigen samples would be the optimal surveillance strategy to accurately detect both concordant and discordant variants.…”

Section: Discussionmentioning

confidence: 99%

Impact of antigen test target failure and testing strategies on the transmission of SARS-CoV-2 variants

et al. 2022

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Population testing remains central to COVID-19 control and surveillance, with countries increasingly using antigen tests rather than molecular tests. Here we describe a SARS-CoV-2 variant that escapes N antigen tests due to multiple disruptive amino-acid substitutions in the N protein. By fitting a multistrain compartmental model to genomic and epidemiological data, we show that widespread antigen testing in the Italian region of Veneto favored the undetected spread of the antigen-escape variant compared to the rest of Italy. We highlight novel limitations of widespread antigen testing in the absence of molecular testing for diagnostic or confirmatory purposes. Notably, we find that genomic surveillance systems which rely on antigen population testing to identify samples for sequencing will bias detection of escape antigen test variants. Together, these findings highlight the importance of retaining molecular testing for surveillance purposes, including in contexts where the use of antigen tests is widespread.

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Section: Discussionmentioning

confidence: 99%

Impact of antigen test target failure and testing strategies on the transmission of SARS-CoV-2 variants

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Our work highlights the importance of also monitoring N antigen diversity, to assess how new mutations may limit the performance of antigen tests. Finally, it was recently shown that SARS-CoV-2 genome sequencing from antigen tests is possible 41 . If this were to become a widely used surveillance tool, we estimate that sequencing positive and negative ANCOV samples would be the optimal surveillance strategy to accurately detect both concordant and discordant variants.…”

Section: Discussionmentioning

confidence: 99%

Impact of antigen test target failure and testing strategies on the transmission of SARS-CoV-2 variants

Vecchio

Daniels

Brancaccio

et al. 2022

Preprint

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Population testing remains central to COVID-19 control and surveillance, with countries increasingly using antigen tests rather than molecular tests. Here we describe a SARS-CoV-2 variant that escapes N antigen tests due to multiple disruptive amino-acid substitutions in the N protein. By fitting a multistrain compartmental model to genomic and epidemiological data, we show that widespread antigen testing in the Italian region of Veneto favored the undetected spread of the antigen-escape variant compared to the rest of Italy. We highlight novel limitations of widespread antigen testing in the absence of molecular testing for diagnostic or confirmatory purposes. Critically, in the presence of a variant that escapes antigen testing, following up a proportion of negative antigen tests with a molecular test is the optimal testing strategy. Together, these findings highlight the importance of retaining molecular testing for surveillance purposes, also in contexts where the use of antigen tests is widespread.

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“…While a reflexive PCR test after a positive Ag-RDT diagnosis is currently performed to obtain samples suitable for sequencing (and is possible in many tertiary facilities in LMICs), this presents additional cost and logistical barriers. Recent studies showed that SARS-CoV-2 sequencing can be performed using materials obtained from Ag-RDTs performed at point-of-care [33][34][35] . Importantly, whole genomes can be recovered up to eight days after testing, providing opportunities for sequencing to be performed on samples performed through selftesting as well 33 .…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 diagnostic testing rates determine the sensitivity of genomic surveillance programs

Han

Toporowski

Sacks

et al. 2022

Preprint

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Background Genomic surveillance is essential for monitoring the emergence and spread of SARS-CoV-2 variants. SARS-CoV-2 diagnostic testing is the starting point for SARS-CoV-2 genomic sequencing. However, testing rates in many low- and middle-income countries (LMICs) are low (mean = 27 tests/100,000 people/day) and global testing rates are falling in the post-crisis phase of the pandemic, leading to spatiotemporal biases in sample collection. Various public health agencies and academic groups have produced recommendations on sample sizes and sequencing strategies for effective genomic surveillance. However, these recommendations assume very high volumes of diagnostic testing that are currently well beyond reach in most LMICs. Methods To investigate how testing rates, sequencing strategies and the degree of spatiotemporal bias in sample collection impact variant detection and monitoring outcomes, we used an individual-based model to simulate COVID-19 epidemics in a prototypical LMIC. Within the model, we simulated a range of testing rates, accounted for likely testing demand and applied various genomic surveillance strategies, including sentinel surveillance. Findings Diagnostic testing rates play a substantially larger role in monitoring the prevalence and emergence of new variants than the proportion of samples sequenced. To enable timely detection and monitoring of emerging variants, programs should achieve average testing rates of at least 100 tests/100,000 people/day and sequence 5-10% of test-positive specimens, which may be accomplished through sentinel or other routine surveillance systems. Under realistic assumptions, this averages to ~10 samples for sequencing/1,000,000 people/week. Interpretation For countries where testing capacities are low and sample collection is spatiotemporally biased, surveillance programs should prioritize investments in wider access to diagnostic testing to enable more representative sampling, ahead of simply increasing quantities of sequenced samples. Funding European Research Council, the Rockefeller Foundation, and the Governments of Germany, Canada, UK, Australia, Norway, Saudi Arabia, Kuwait, Netherlands and Portugal.

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Sequencing SARS-CoV-2 from antigen tests

Cited by 16 publications

References 15 publications

Impact of antigen test target failure and testing strategies on the transmission of SARS-CoV-2 variants

Impact of antigen test target failure and testing strategies on the transmission of SARS-CoV-2 variants

Impact of antigen test target failure and testing strategies on the transmission of SARS-CoV-2 variants

SARS-CoV-2 diagnostic testing rates determine the sensitivity of genomic surveillance programs

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