Performance of antigen lateral flow devices in the UK during the alpha, delta, and omicron waves of the SARS-CoV-2 pandemic: a diagnostic and observational study

Abstract

Background: Antigen lateral flow devices (LFDs) have been widely used to control SARS-CoV-2. We aimed to improve understanding of LFD performance with changes in variant infections, vaccination, viral load, and LFD use, and in the detection of infectious individuals.

Methods: In this diagnostic study, paired LFD and RT-PCR test results were prospectively collected from asymptomatic and symptomatic participants in the UK between Nov 4, 2020, and March 21, 2022, to support the National Health Service (NHS) England's Test and Trace programme. The LFDs evaluated were the Innova SARS-CoV-2 Antigen Rapid Qualitative Test, the Orient Gene Rapid Covid-19 (Antigen) Self-Test, and the Acon Flowflex SARS-CoV-2 Antigen Rapid Test (Self-Testing). Test results were collected across various community testing settings, including predeployment testing sites, routine testing centres, homes, schools, universities, workplaces, targeted community testing, and from health-care workers. We used multivariable logistic regression to analyse LFD sensitivity and specificity using RT-PCR as a reference standard, adjusting for viral load, LFD manufacturer, test setting, age, sex, test assistance, symptom status, vaccination status, and SARS-CoV-2 variant. National contact tracing data from NHS Test and Trace (Jan 1, 2021, to Jan 11, 2022) were used to estimate the proportion of transmitting index patients (with ≥1 RT-PCR-positive or LFD-positive contact) potentially detectable by LFDs (specifically Innova, as the most widely used LFD) with time, accounting for index viral load, variant, and symptom status.

Findings: We assessed 75 382 pairs of LFD and RT-PCR tests. Of these, 4131 (5·5%) were RT-PCR-positive. LFD sensitivity versus RT-PCR was 63·2% (95% CI 61·7-64·6) and specificity was 99·71% (95% CI 99·66-99·74). Increased viral load was independently associated with being LFD positive (adjusted odds ratio [aOR] 2·85 [95% CI 2·66-3·06] per 1 log₁₀ copies per mL increase; p<0·0001). There was no evidence that LFD sensitivity differed for delta (B.1.617.2) infections versus alpha (B.1.1.7) or pre-alpha (B.1.177) infections (aOR 1·00 [0·69-1·45]; p=0·99), whereas omicron (BA.1 or BA.2) infections appeared more likely to be LFD positive (aOR 1·63 [1·02-2·59]; p=0·042). Sensitivity was higher in symptomatic participants (68·7% [95% CI 66·9-70·4]) than in asymptomatic participants (52·8% [50·1-55·4]). Among 347 374 unique index patients with probable onward transmission, 78·3% (95% CI 75·3-81·2) were estimated to have been detectable with LFDs (Innova), and this proportion was mostly stable with time and for successive variants. Overall, the estimated proportion of infectious index patients detectable by the Innova LFD was lower in asymptomatic patients (57·6% [53·6-61·9]) versus symptomatic patients (79·7% [76·7-82·5]).

Interpretation: LFDs remained able to detect most SARS-CoV-2 infections throughout vaccine roll-out and across different viral variants. LFDs can potentially detect most infections that transmit to others and reduce the risk of transmission. However, performance is lower in asymptomatic individuals than in symptomatic individuals.

Funding: UK Health Security Agency, the UK Government Department of Health and Social Care, National Institute for Health Research (NIHR) Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, and the University of Oxford NIHR Biomedical Research Centre.

Figure 1

SARS-CoV-2 RT-PCR-positive samples used in lateral flow device evaluation by setting and viral variant The source of the assigned SARS-CoV-2 variant is also shown by colour gradient. Seven RT-PCR-positive results from workplaces, obtained between April 27 and Sept 1, 2021, are not shown.

Figure 2

Sensitivity of SARS-CoV-2 LFDs by viral load and patient symptoms The model predictions plotted are adjusted for test setting (predictions are shown for unselected community-based testing), assistance performing the test (self-performed), vaccination status (unvaccinated), and variant (alpha [B.1.1.7] or pre-alpha [B1.1.177]). In addition to the model shown in table 1, an interaction term between viral load and LFD was included to allow the shape of the curves to vary by device. A comparison with observed data is presented in the appendix (p 7). LFD=lateral flow device.

Figure 3

Index patient Ct values and the probability of tested contacts being RT-PCR positive or LFD positive (A) and estimated index cases detectable by LFDs among case–contact pairs with probable transmission (B) Contacts of asymptomatic index patients were 0·76 times as likely to test positive as contacts of symptomatic index patients at a Ct value of 10; 0·70 times as likely at a Ct value of 20; and 0·65 times as likely at a Ct value of 30. The model in part A was adjusted for index patient age (predictions plotted for age 40 years), index patient sex (female), index patient vaccination status (boosted, ≥3 vaccine doses), contact event type (household or accommodation), contact age (40 years), contact sex (female), and index test date (July 1, 2021). We found no evidence that fitting an interaction between index patient symptom status and Ct values improved model fit. In part B, error bars indicate 95% CIs calculated by non-parametric bootstrapping (1000 iterations). Ct=cycle threshold. LFD=lateral flow device.