Lateral flow immunoassays (LFIAs) are being used worldwide for COVID-19 mass testing and antibody prevalence studies. Relatively simple to use and low cost, these tests can be self-administered at home, but rely on subjective interpretation of a test line by eye, risking false positives and false negatives. Here, we report on the development of ALFA (Automated Lateral Flow Analysis) to improve reported sensitivity and specificity.
Our computational pipeline uses machine learning, computer vision techniques and signal processing algorithms to analyse images of the Fortress LFIA SARS-CoV-2 antibody self-test, and subsequently classify results as invalid, IgG negative and IgG positive. A large image library of 595,339 participant-submitted test photographs was created as part of the REACT-2 community SARS-CoV-2 antibody prevalence study in England, UK. Alongside ALFA, we developed an analysis toolkit which could also detect device blood leakage issues.
Automated analysis showed substantial agreement with human experts (Cohen’s kappa 0.90–0.97) and performed consistently better than study participants, particularly for weak positive IgG results. Specificity (98.7–99.4%) and sensitivity (90.1–97.1%) were high compared with visual interpretation by human experts (ranges due to the varying prevalence of weak positive IgG tests in datasets).
Given the potential for LFIAs to be used at scale in the COVID-19 response (for both antibody and antigen testing), even a small improvement in the accuracy of the algorithms could impact the lives of millions of people by reducing the risk of false-positive and false-negative result read-outs by members of the public. Our findings support the use of machine learning-enabled automated reading of at-home antibody lateral flow tests as a tool for improved accuracy for population-level community surveillance.
Plain language summary
During the COVID-19 pandemic, antibody test kits, for use at home, were used to estimate how many people had COVID antibodies. These estimations indicated how many people have been exposed to the virus or have antibodies due to vaccination. However, some positive test results can be very faint, and be mistaken as negative. In our work, 500,000 people reported their antibody test results and submitted a photograph of their test. We designed a computerised system—a highly specialised artificial-intelligence (AI) system—that has high agreement with experts and can highlight potential mistakes by the public in reading the results of their home tests. This AI system makes it possible to improve the accuracy of monitoring COVID antibodies at the population level (e.g. whole country), which could inform decisions on public health, such as when booster vaccines should be administered.
Bibliographical noteThis work was funded by the Department of Health and Social Care in England. The content of this manuscript and decision to submit for publication were the responsibility of the authors and the funders had no role in these decisions. H.W. is a NIHR Senior Investigator and acknowledges support from NIHR Biomedical Research Centre of Imperial College NHS Trust, NIHR School of Public Health Research, NIHR Applied Research Collaborative North West London, Wellcome Trust (UNS32973). G.C. is supported by an NIHR Professorship and the NIHR Imperial Biomedical Research Centre. W.B. is the Action Medical Research Professor and A.D. is an NIHR senior investigator. P.E. is Director of the MRC Centre for Environment and Health (MR/L01341X/1, MR/S019669/1). P.E. acknowledges support from the NIHR Imperial Biomedical Research Centre and the NIHR HPRUs in Chemical and Radiation Threats and Hazards, and Environmental Exposures and Health, the British Heart Foundation Centre for Research Excellence at Imperial College London (RE/18/4/34215), the UK Dementia Research Institute at Imperial (MC_PC_17114) and Health Data Research UK (HDR UK). R.A.M., V.T. and S.M. were funded by the i-sense EPSRC IRC in Agile Early Warning Sensing Systems for Infectious Diseases and Antimicrobial Resistance and associated COVID Plus Award (no. EP/R00529X/1). R.A.M and S.M. were supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. This work was also supported by the NTU-Imperial Research Collaboration Fund and the EPSRC Impact Acceleration Award (EP/R511547/1). We thank key collaborators on this work—Ipsos MORI: Stephen Finlay and Duncan Peskett; School of Public Health at Imperial College London: Eric Johnson and Rob Elliot; the Imperial Patient Experience Research Centre and the REACT Public Advisory Panel.
Data Availability StatementFor the underlying data, access to this data is restricted due to ethical and security considerations. To obtain ethics approval from the South Central Berkshire B Research Ethics Committee (REC) and Health Regulator Authority (HRA), we agreed that we will preserve the confidentiality of participants taking part in the study and fulfil transparency requirements under the General Data Protection Regulation for health and care research. We also agreed that all REACT study data is to be held securely and processed in a Secure Enclave. This is an isolated environment within Imperial College for the processing of health-related personal data. It provides a framework that satisfies Information Governance requirements that come from several sources.
The Secure Enclaves are compliant with the requirements of major data providers (e.g. ONS, NHS Digital and NHS Trusts), as well as flexible to incorporate additional requirements a group may be subject to. The enclaves are ISO27001 certified.
These restrictions apply to all the study data, both qualitative and quantitative. We do not allow any line list data to be taken from the secure enclave because of the risk of cross-referencing and deductive disclosure. A researcher can request access to the data held in the Secure Enclave by emailing email@example.com. Access would be granted to researchers for the purposes of further research subject to approval by the data access committee and after signing a data access agreement to ensure no disclosure of potentially identifying details.