A response to 'Covid-19: government must urgently rethink lateral flow test roll-out': lateral flow testing in contact tracing
We write in response to the blog post ‘Covid-19: government must urgently rethink lateral flow test roll-out' by J Deeks, A Raffle and M Gill, which cited a rapid report on the use of lateral flow device (LFD) testing in contact tracing, which we wrote for SAGE.
We agree with the authors that, as with any public health intervention, potential harms of the different uses of SARS-CoV-2 LFD tests for COVID-19 epidemic control should be considered and evaluated. We also agree that modelling should complement real-world evidence about LFD test use across diverse population groups. In turn, these assessments need to be considered alongside the significant challenges in identifying cases within the existing PCR symptomatic testing programme[3,4].
However, the authors appear to have missed two fundamental points in our analysis of the implementation of LFD testing, important to the discussion of their utility: the dynamics of viral load, infectiousness and LFD test sensitivity over time; and the specific use of daily LFD testing on contacts of a confirmed case.
Understanding the dynamics of test sensitivity over the course of infection is key. The authors incorrectly state that we modelled LFD test sensitivity as random. Instead, we modelled PCR and LFD test sensitivity as a function of time since infection, which is broadly equivalent to measuring test sensitivity as a function of viral load. We did not correlate sensitivity within the same individuals over time; we agree this could be considered. Studies show that viral load post-infection is initially low, then rapidly increases, peaking just prior to symptom onset on average 4-5 days post-infection (with variation between 2-14 days), before declining[5,6]. Compared to PCR, the sensitivity of the Innova LFD tests over the period during which one could test positive on PCR has been estimated at 40% to 79%, depending on who is conducting the swabbing and degree of training in assessing test results. The key point here is that the sensitivity of LFD tests compared to PCR is higher at higher viral loads: 82% cumulative sensitivity at cycle thresholds (CT) <20 and 67% at CT<25 in the Liverpool study, (re-appraised to 90% and 83% respectively with training) . Conversely, LFD sensitivity is much lower compared to PCR when CT values are high and viral load is low. This is important to the design of LFD testing regimes, and because current scientific evidence suggests that when viral loads are lower so is infectiousness[9-11].
The timing of test sensitivity implies that an ideal LFD testing regime to identify, isolate and trace true infections as early in their infection as possible, benefits from incorporating repeat-testing. Testing should start soon after exposure, with duration sufficient to allow for variation in the incubation period and repetition over the peak period of infectiousness, to help compensate for imperfect sensitivity even at this time. Where exposure is constant, as for frontline workers, repeat-testing at short intervals should be considered.
We are concerned that all potential applications of LFD testing have become conflated in the scientific debate relating to their utility. Like any test, there are more or less appropriate applications. Deeks et al omit to mention that we specifically investigated the potential effects on epidemic growth of using repeat LFD testing among contacts of a confirmed case. Effectiveness of contact tracing and isolation is dependent on finding a high proportion of cases and isolating them early to break chains of transmission. Yet, even among those experiencing symptoms of COVID-19, over half in the UK are estimated to have never tested. Among cases who are detected and enabled to effectively isolate via symptomatic PCR testing, a large proportion of their likely onwards transmission is missed when those cases are not identified until they have become symptomatic, decided to test, booked a test and received test results. The current UK policy of only testing contacts of a case, a high-risk group for infection, if they develop symptoms and tracing their contacts after another set of testing delays, perpetuates inefficiency over generations of infection. A strategy of repeated LFD tests with rapid results could, with prompt tracing, find more cases and earlier in their infections so that they could be supported to isolate. There is potentially a cumulative, onwards benefit to tracing to enable better epidemic control.
More broadly, current and future LFD testing strategies should be considered in terms of: 1) the population among whom they are to be used; 2) the purposes of the test; 3) the testing regime (one-off or serial, duration and frequency if repeated); and 4) the messaging that accompanies the test, which may influence behaviour. For instance, a one-off test to enable visiting elderly relatives, should be considered a separate, and potentially riskier, use case to what we have investigated. The success of each use case will depend on their delivery as part of a tailored package of interventions that includes consideration of the communication of positive and negative test results, and support to enable optimal and equitable uptake of testing, and of isolation amongst those positive.
Finally, to clarify, we are a cross-disciplinary group of independent academics funded by a UKRI/NIHR COVID-19 rapid response grant. Along with many other groups, we report findings via scientific advisory channels (SPI-M, SPI-B, SAGE), but are not ‘the government’s TTI modelling group’, as we have been described.
Elizabeth Fearon, PI UKRI/NIHR COVID-19 Rapid Response Rolling Call grant MR/V028618/1, a.k.a the TTI Modelling Group.
Emma L Davis
Helena B Stage
1 Deeks J, Raffle A, Gill M. Covid-19: government must urgently rethink lateral flow test roll out. BMJ Opin Published Online First: 12 January 2021. https://blogs.bmj.com/bmj/2021/01/12/covid-19-government-must-urgently-r... (accessed 20 Jan 2021).
2 Fearon E, Fyles M, TTI Modelling Group. On the use of LFA tests in contact tracing: preliminary findings. https://assets.publishing.service.gov.uk/government/uploads/system/uploa... (accessed 20 Jan 2021).
3 Smith LE, Potts HWW, Amelot R, et al. Adherence to the test, trace and isolate system: results from a time series of 21 nationally representative surveys in the UK (the COVID-19 Rapid Survey of Adherence to Interventions and Responses [CORSAIR] study). medRxiv 2020.09.15.20191957. doi:10.1101/2020.09.15.20191957
4 Fancourt D, Bu F, Mak HW, et al. Covid-19 Social Study Results Release 28. 2021.https://b6bdcb03-332c-4ff9-8b9d-28f9c957493a.filesusr.com/ugd/3d9db5_bf0... (accessed 20 Jan 2021).
5 Meyerowitz EA, Richterman A, Gandhi RT, et al. Transmission of SARS-CoV-2: A Review of Viral, Host, and Environmental Factors. Ann Intern Med 2021;174:69–79. doi:10.7326/M20-5008Dear Editor,
6 Cevik M, Kuppalli K, Kindrachuk J, et al. Virology, transmission, and pathogenesis of SARS-CoV-2. BMJ 2020;371:m3862. doi:10.1136/bmj.m3862
7 Liverpool Covid-19 Community Testing Pilot: Interim Evaluation Report. University of Liverpool, Department of Health and Social Care 2020. https://www.liverpool.ac.uk/media/livacuk/coronavirus/Liverpool,Communit... (accessed 20 Jan 2021).
8 Preliminary report from the Joint PHE Porton Down & University of Oxford SARS-CoV-2 test development and validation cell: Rapid evaluation of Lateral Flow Viral Antigen detection devices (LFDs) for mass community testing. Public Health England, University of Oxford 2020. https://www.ox.ac.uk/sites/files/oxford/media_wysiwyg/UK%20evaluation_PH... (accessed 20 Jan 2021).
9 van Kampen JJA, van de Vijver DAMC, Fraaij PLA, et al. Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19). Nat Commun 2021;12:267. doi:10.1038/s41467-020-20568-4
10 Singanayagam A, Patel M, Charlett A, et al. Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19, England, January to May 2020. Euro Surveill Bull Eur Sur Mal Transm Eur Commun Dis Bull 2020;25. doi:10.2807/1560-7917.ES.2020.25.32.2001483
11 La Scola B, Le Bideau M, Andreani J, et al. Viral RNA load as determined by cell culture as a management tool for discharge of SARS-CoV-2 patients from infectious disease wards. Eur J Clin Microbiol Infect Dis 2020;39:1059–61. doi:10.1007/s10096-020-03913-9
12 Waller J, Rubin GJ, Potts HWW, et al. Immunity Passports’ for SARS-CoV-2: an online experimental study of the impact of antibody test terminology on perceived risk and behaviour. BMJ Open 2020;10.
Competing interests: Elizabeth Fearon is the Principal Investigator of UKRI/NIHR COVID-19 Rapid Response Rolling Call grant MR/V028618/1, 'An analytical framework for Test, Trace and Isolate in the UK'.