Evaluation of serological lateral flow assays for severe acute respiratory syndrome coronavirus-2

Trombetta, B. A.; Kandigian, S. E.; Kitchen, R. R.; Grauwet, K.; Webb, P. K.; Miller, G. A.; Jennings, C. G.; Jain, S.; Miller, S. M.; Kuo, Y.; Sweeney, T.; Gilboa, T.; Norman, M.; Simmons, D. P.; Ramirez, C. E.; Bedard, M.; Fink, C.; Ko, J.; Peralta, E. J. D. L.; Watts, G.; Gomez-Rivas, E.; Davis, V.; Barilla, R.; Wang, J.; Cunin, P.; Bates, S.; Morrison-Smith, C.; Nicholson, B.; Wong, E.; El-Mufti, L.; Kann, M.; Bolling, A.; Fortin, B.; Ventresca, H.; Zhou, W.; Pardo, S.; Kwock, M.; Hazra, A.; Cheng, L.; Ahmad, R.; Toombs, J. A.; Larson, R.; Pleskow, H.; Luo, N. M.; Samaha, C.; Pandya, U. M.

Background: COVID-19 has resulted in significant morbidity and mortality worldwide. Lateral flow assays can detect anti-Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) antibodies to monitor transmission. However, standardized evaluation of their accuracy and tools to aid in interpreting results are needed. Methods: We evaluated 20 IgG and IgM assays selected from available tests in April 2020. We evaluated the assays performance using 56 pre-pandemic negative and 56 SARS-CoV-2-positive plasma samples, collected 10-40 days after symptom onset, confirmed by a molecular test and analyzed by an ultra-sensitive immunoassay. Finally, we developed a user-friendly web app to extrapolate the positive predictive values based on their accuracy and local prevalence. Results: Combined IgG+IgM sensitivities ranged from 33.9% to 94.6%, while combined specificities ranged from 92.6% to 100%. The highest sensitivities were detected in Lumiquick for IgG (98.2%), BioHit for both IgM (96.4%), and combined IgG+IgM sensitivity (94.6%). Furthermore, 11 LFAs and 8 LFAs showed perfect specificity for IgG and IgM, respectively, with 15 LFAs showing perfect combined IgG+IgM specificity. Lumiquick had the lowest estimated limit-of-detection (LOD) (0.1 g/mL), followed by a similar LOD of 1.5 g/mL for CareHealth, Cellex, KHB, and Vivachek. Conclusion: We provide a public resource of the accuracy of select lateral flow assays with potential for home testing. The cost-effectiveness, scalable manufacturing process, and suitability for self-testing makes LFAs an attractive option for monitoring disease prevalence and assessing vaccine responsiveness. Our web tool provides an easy-to-use interface to demonstrate the impact of prevalence and test accuracy on the positive predictive values.