Clarifying the evidence on SARS-CoV-2 antigen rapid tests in public health responses to COVID-19

Mina, Michael J.; Peto, Tim; Garcı́a-Fiñana, Marta; Semple, Malcolm G; Buchan, Iain

doi:10.1016/s0140-6736(21)00425-6

Cited by 160 publications

(181 citation statements)

References 29 publications

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“…Future work will explore the relationship between patterns of FMS output of SARS-CoV-2 and transmission to determine the value of this approach in determining infectivity of individuals, compared to other tests proposed for similar purposes, such as the lateral flow assays. 22…”

Section: Discussionmentioning

confidence: 99%

Exhaled SARS-CoV-2 quantified by face-mask sampling in hospitalised patients with covid-19

Williams

Pan²,

Decker³

et al. 2020

Preprint

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Background Nasopharyngeal samples (NPS) are the mainstay of COVID-19 diagnosis. However, the extent to which assay signals relate to exhaled virus is unknown. We investigated the use of novel, non-invasive face-mask sampling (FMS) to detect exhaled SARS-CoV-2 RNA in two studies. Methods In an outbreak study (cohort 1), we performed FMS and NPS for 21 consecutive days after diagnosis on six healthcare workers who were screened positive for SARS-CoV-2. In a second hospitalised cohort (cohort 2), we performed FMS on 47 patients within 24 hours of a positive diagnosis. COVID-19 severity was graded according to WHO recommendations. Findings In cohort 1, SARS-COV-2 was detected by FMS in 10/40 (25%) samples (4/6 individuals), with no correlation between NPS and FMS RNA signals. All samples were negative by day 14 post diagnosis. Sustained FMS positivity with higher viral RNA signals showed a trend towards disease severity. In cohort 2, 19/47 (40%) individuals exhaled SARS-CoV-2 RNA extending over five orders of magnitude. FMS positive participants were older (positive: median age [IQR] 71 [61-84] vs negative: 61 [45-73], p=0.04) with more comorbidities (positive: 2 [1-3] vs negative: 1 [0-2], p<0.001) and have active cough (positive: 68% vs negative: 24%, p=0.003) and breathlessness (positive: 74% vs negative: 32%, p=0.005) during sampling, compared to FMS negative patients. Of five patients who were FMS positive and asymptomatic at time of sampling, two died of severe COVID-19 pneumonia within one month of follow up. Interpretation FMS detects exhaled SARS-COV-2, with stronger signals in those who develop severe disease.

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Section: Discussionmentioning

confidence: 99%

Exhaled SARS-CoV-2 quantified by face-mask sampling in hospitalised patients with covid-19

Williams

Pan²,

Decker³

et al. 2020

Preprint

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“…These tests are less sensitive than real-time reverse transcription polymerase chain reaction (RT-PCR) and other nucleic amplification technology 3 . Preliminary results on the Liverpool pilot study with Innova lateral flow test (LFT) indicated that this assay had a sensitivity of 66% 4 and an even lower 49% 5 sensitivity was reported in other community testing in UK. A screening with the same test performed on the students at Birmingham University reported a worryingly low sensitivity of 3.2% amongst asymptomatic young individuals 4,6 .…”

Section: Introductionmentioning

confidence: 99%

“…Preliminary results on the Liverpool pilot study with Innova lateral flow test (LFT) indicated that this assay had a sensitivity of 66% 4 and an even lower 49% 5 sensitivity was reported in other community testing in UK. A screening with the same test performed on the students at Birmingham University reported a worryingly low sensitivity of 3.2% amongst asymptomatic young individuals 4,6 . It has been argued that this discrepancy was possibly due to the lower viral loads of Birmingham students compared with those examined at Liverpool.…”

Section: Introductionmentioning

confidence: 99%

Emergence of N antigen SARS-CoV-2 genetic variants escaping detection of antigenic tests

Vecchio

Brancaccio

Brazzale

et al. 2021

Preprint

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SARS-CoV-2 genetic variants are emerging as a major threat to vaccination efforts worldwide as they may increase virus transmission rate and/or confer the ability to escape vaccine induced immunity with knock on effects on the level of herd immunity and vaccine efficacy respectively. These variants concern the Spike protein, which is encoded by the S gene, involved in virus entry into host cells and the major target of vaccine development. We report here that genetic variants of the N gene can impair our ability to utilize antigenic tests for both diagnosis and mass testing efforts aimed at controlling virus transmission. While conducting a large validation study on the Abbott Panbio COVID-19 Ag test, we noticed that some swab samples failed to generate a positive result in spite of a high viral load in Rt-PCR assays. Sequencing analysis of viruses showing discordant results in the Rt-PCR and antigen assays revealed the presence of multiple disruptive amino-acid substitutions in the N antigen (the viral protein detected in the antigen test) clustered from position 229 to 374 a region known to contain an immunodominant epitope. A relevant fraction of the variants, undetected by the antigen test, contained the mutations A376T coupled to M241I. Intriguingly we found that virus sequences with this mutation were over-represented in the antigen-test-negative and PCR-positive samples and progressively increased in frequency over time in Veneto, a region of Italy that has aggressively scaled up the utilization of antigen tests, which reached nearly 68% of all the SARS-CoV-2 swab assays performed there. We speculate that mass utilization of antigen assays could create a selection pressure on the target that may favor the spread of undetectable virus variants.

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“…When LFTs are conducted by trained staff and volunteers, however, sensitivity for SARS-CoV-2 detection is roughly 50% compared with PCR tests 58,68,69 , and their performance when used for home testing is not well documented. In general, the false negative rate is lower for individuals with high viral loads, who are likely to be most infectious 65 . Nonetheless, the difference in secondary attack rates amongst household contacts of index cases with high or low CT values observed in our study suggests that this gradient in infectiousness may be modest, consistent with variability in serial sampling 53,70 , laboratory data on recovery of infectious virus 55 , and analysis of contact tracing data 71 .…”

Section: Discussionmentioning

confidence: 98%

“…Moreover, swab pooling effectively increases the prevalence of true positive samples. In theory, the high sensitivity of PCR tests could result in the detection of individuals with low levels of viral RNA late in their course of infection, even when they are no longer infectious 65 . Whilst this is a valid concern for one-off mass testing, it is not relevant for programmes based on regular, frequent screening.…”

Section: Discussionmentioning

confidence: 99%

Feasibility and efficacy of mass testing for SARS-CoV-2 in a UK university using swab pooling and PCR

Warne¹,

Enright²,

Metaxaki³

et al. 2021

Preprint

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Transmission of SARS-CoV-2 without symptoms is well described, and may be mitigated by mass testing. Nonetheless, the optimal implementation and quantitative real-world impact of this approach remain unclear. During a period of rising SARS-CoV-2 prevalence, students at the University of Cambridge were enrolled in a voluntary programme of weekly PCR-based asymptomatic screening. Swab pooling by household reduced the total testing capacity required by five-fold, without affecting laboratory workflows or compromising test sensitivity. Participation remained >75% throughout the study period. 299/671 (45%) of students diagnosed with SARS-CoV-2 were either identified or pre-emptively quarantined because of the screening programme. After a negative screening test, the risk of developing COVID-19 over the following 7 days was decreased by 51%. Modelling transmission using parameters from our study suggests a reduction in R0 of up to 31% attributable to weekly screening. We therefore demonstrate the feasibility and efficacy of regular, voluntary mass testing for COVID-19.

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Clarifying the evidence on SARS-CoV-2 antigen rapid tests in public health responses to COVID-19

Cited by 160 publications

References 29 publications

Exhaled SARS-CoV-2 quantified by face-mask sampling in hospitalised patients with covid-19

Exhaled SARS-CoV-2 quantified by face-mask sampling in hospitalised patients with covid-19

Emergence of N antigen SARS-CoV-2 genetic variants escaping detection of antigenic tests

Feasibility and efficacy of mass testing for SARS-CoV-2 in a UK university using swab pooling and PCR

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