A Lateral Flow Immunoassay Coupled with a Spectrum-Based Reader for SARS-CoV-2 Neutralizing Antibody Detection

Rui-Lin Huang; Yi-Chen Fu; Yung-Chih Wang; Chitsung Hong; Wei-Chieh Yang; I-Jen Wang; Jun-Ren Sun; Yunching Chen; Ching-Fen Shen; Chao-Min Cheng

doi:10.3390/vaccines10020271

A Lateral Flow Immunoassay Coupled with a Spectrum-Based Reader for SARS-CoV-2 Neutralizing Antibody Detection

Vaccines (Basel). 2022 Feb 10;10(2):271. doi: 10.3390/vaccines10020271.

Authors

Rui-Lin Huang¹, Yi-Chen Fu¹, Yung-Chih Wang², Chitsung Hong³, Wei-Chieh Yang⁴, I-Jen Wang^{5

6

7}, Jun-Ren Sun⁸, Yunching Chen¹, Ching-Fen Shen^{9

10}, Chao-Min Cheng¹

Affiliations

¹ Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan.
² National Defense Medical Center, Department of Internal Medicine, Division of Internal Medicine and Tropical Medicine, Tri-Service General Hospital, Taipei 11490, Taiwan.
³ Spectrochip Inc., Hsinchu 302059, Taiwan.
⁴ Ping An Medical Clinic, Tainan 708, Taiwan.
⁵ Department of Pediatrics, Taipei Hospital, Ministry of Health and Welfare, New Taipei City 24213, Taiwan.
⁶ College of Public Health, China Medical University, Taichung 406040, Taiwan.
⁷ School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan.
⁸ National Defense Medical Center, Institute of Preventive Medicine, Taipei 23742, Taiwan.
⁹ Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
¹⁰ Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.

Abstract

As of August 2021, there have been over 200 million confirmed case of coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus and more than 4 million COVID-19-related deaths globally. Although real-time polymerase chain reaction is considered to be the primary method of detection for SARS-CoV-2 infection, the use of serological assays for detecting COVID-19 antibodies has been shown to be effective in aiding with diagnosis, particularly in patients who have recovered from the disease and those in later stages of infection. Since it has a high detection rate and few limitations compared to conventional enzyme-linked immunosorbent assay protocols, we used a lateral flow immunoassay as our diagnostic tool of choice. Since lateral flow immunoassay results interpreted by the naked eye may lead to erroneous diagnoses, we developed an innovative, portable device with the capacity to capture a high-resolution reflectance spectrum as a means of promoting diagnostic accuracy. We combined this spectrum-based device with commercial lateral flow immunoassays to detect the neutralizing antibody in serum samples collected from 30 COVID-19-infected patients (26 mild cases and four severe cases). The results of our approach, lateral flow immunoassays coupled with a spectrum-based reader, demonstrated a 0.989 area under the ROC curve, 100% sensitivity, 95.7% positive predictive value, 87.5% specificity, and 100% negative predictive value. As a result, our approach exhibited great value for neutralizing antibody detection. In addition to the above tests, we also tested plasma samples from 16 AstraZeneca-vaccinated (ChAdOx1nCoV-19) patients and compared our approach and enzyme-linked immunosorbent assay results to see whether our approach could be applied to vaccinated patients. The results showed a high correlation between these two approaches, indicating that the lateral flow immunoassay coupled with a spectrum-based reader is a feasible approach for diagnosing the presence of a neutralizing antibody in both COVID-19-infected and vaccinated patients.

Keywords: AstraZeneca; coronavirus disease 2019 (COVID-19); lateral flow immunoassay; neutralizing antibody; severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).