SARS-CoV-2 antigen lateral flow tests for detecting infectious people: linked data analysis

Abstract Objectives To investigate the proportion of lateral flow tests (LFTs) that produce negative results in those with a high risk of infectiousness from SARS-CoV-2, to investigate the impact of the stage and severity of disease, and to compare predictions made by influential mathematical models with findings of empirical studies. Design Linked data analysis combining empirical evidence of the accuracy of the Innova LFT, the probability of positive viral culture or transmission to secondary cases, and the distribution of viral loads of SARS-CoV-2 in individuals in different settings. Setting Testing of individuals with symptoms attending NHS Test-and-Trace centres across the UK, residents without symptoms attending municipal mass testing centres in Liverpool, and students without symptoms screened at the University of Birmingham. Participants Evidence for the sensitivity of the Innova LFT, based on 70 individuals with SARS-CoV-2 and LFT results. Infectiousness was based on viral culture rates on 246 samples (176 people with SARS-CoV-2) and secondary cases among 2 474 066 contacts; distributions of cycle threshold (Ct) values from 231 497 index individuals attending NHS Test-and-Trace centres; 70 people with SARS-CoV-2 detected in Liverpool and 62 people with SARS-CoV-2 in Birmingham (54 imputed). Main outcome measures The predicted proportions who were missed by LFT and viral culture positive and missed by LFT and sources of secondary cases, in each of the three settings. Predictions were compared with those made by mathematical models. Results The analysis predicted that of those with a viral culture positive result, Innova would miss 20% attending an NHS Test-and-Trace centre, 29% without symptoms attending municipal mass testing, and 81% attending university screen testing without symptoms, along with 38%, 47%, and 90% of sources of secondary cases. In comparison, two mathematical models underestimated the numbers of missed infectious individuals (8%, 10%, and 32% in the three settings for one model, whereas the assumptions from the second model made it impossible to miss an infectious individual). Owing to the paucity of usable data, the inputs to the analyses are from limited sources. Conclusions The proportion of infectious people with SARS-CoV-2 missed by LFTs is substantial enough to be of clinical importance. The proportion missed varied between settings because of different viral load distributions and is likely to be highest in those without symptoms. Key models have substantially overestimated the sensitivity of LFTs compared with empirical data. An urgent need exists for additional robust well designed and reported empirical studies from intended use settings to inform evidence based policy.