Evaluation of Serological SARS-CoV-2 Lateral Flow Assays for Rapid Point-of-Care Testing

Abstract

Background. Rapid point-of-care tests (POCTs) for SARS-CoV-2-specific antibodies vary in performance. A critical need exists to perform head-to-head comparison of these assays. Methods. Performance of fifteen different lateral flow POCTs for the detection of SARS-CoV-2-specific antibodies was performed on a well characterized set of 100 samples. Of these, 40 samples from known SARS-CoV-2-infected, convalescent individuals (average of 45 days post symptom onset) were used to assess sensitivity. Sixty samples from the pre-pandemic era (negative control), that were known to have been infected with other respiratory viruses (rhinoviruses A, B, C and/or coronavirus 229E, HKU1, NL63 OC43) were used to assess specificity. The timing of seroconversion was assessed on five LFAs on a panel of 272 longitudinal samples from 47 patients of known time since symptom onset. Results. For the assays that were evaluated, the sensitivity and specificity for any reactive band ranged from 55%-97% and 78%-100%, respectively. When assessing the performance of the IgM and the IgG bands alone, sensitivity and specificity ranged from 0%-88% and 80%-100% for IgM and 25%-95% and 90%-100% for IgG. Longitudinal testing revealed that median time post symptom onset to a positive result was 7 days (IQR 5.4, 9.8) for IgM and 8.2 days (IQR 6.3 to 11.3) for IgG. Conclusion. The testing performance varied widely among LFAs with most variation related to the sensitivity of the assays. The IgM band was most likely to misclassify pre-pandemic samples. The appearance of IgM and IgG bands occurred almost simultaneously.

SARS-CoV-2 lateral flow assays for possible use in national covid-19 seroprevalence surveys (React 2): diagnostic accuracy study

“…Laboratory testing is an essential component of LFIA evaluation. 15 18 In this study, as in previous work, we have shown that most LFIAs evaluated had lower sensitivity or specificity than reported in preliminary results by the manufacturers. Only three LFIAs in round 2, and eight of 18 LFIAs evaluated in the React 2 programme to date showed sufficient sensitivity and specificity during analysis on sera to justify progression to clinic testing.…”

“… 17 An accurate assessment of the performance of LFIAs with capillary blood is key to interpreting large scale seroprevalence studies, and before clinical implementation, given the reduced sensitivity compared with laboratory analysis for some tests. 4 18 …”

Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Status in Decedents Undergoing Forensic Postmortem Examination in Maryland, May 24 to June 30, 2020

“…Finally, other antibody tests (eg, enzyme-linked immunosorbent assay [ELISA]) may have produced different results. The rapid flow assay utilized has validated high sensitivity and specificity and is relatively cheap and easy to perform and has been compared with numerous ELISAs for comparison of our results to forthcoming seroprevalence studies that utilize ELISAs [ 7 ].…”

“…Severe acute respiratory syndrome coronavirus-2 immunoglobulin (Ig)M and IgG antibodies were detected using the CoronaChek serologic lateral flow assay (purchased from CLIAwaived and made by Hangzhou Biotest Bioctech Co., Ltd.). Studies of CoronaChek on positive and negative control specimens from Maryland showed good sensitivity (95%; 95% confidence interval [CI], 83%–99% in convalescent plasma donors >28 days after symptom onset; 100% [95% CI, 89%–100%] in COVID-19-confirmed hospitalized individuals 15 days after symptom onset) and specificity (100% [95% CI, 94%–100%] in patients infected with rhinoviruses and other coronaviruses before the COVID-19 pandemic) [ 7 ].…”

Use of dried blood spot samples for SARS-CoV-2 antibody detection using the Roche Elecsys ® high throughput immunoassay

“…However, extensive population testing is not feasible using the currently available, highly sensitive immunoassays, due to the need to take venous blood samples. As such, serosurveillance using home sampling is currently limited to the use of lateral flow immunoassays (LFIAs), which often have limited sensitivity [ [1] , [2] , [3] , [4] , [5] ].…”