Evaluation of serological lateral flow assays for severe acute respiratory syndrome coronavirus-2
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Abstract
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 μg/mL), followed by a similar LOD of 1.5 μg/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.
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SciScore for 10.1101/2021.01.02.20248998: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The study was approved under the Massachusetts General Brigham (MGB) Institutional Review Board (protocol no. 2020P001204) Randomization Pre-pandemic negative control samples were randomly selected from healthy participants with a Charlson Age-Comorbidity Index38 score ≤2, with EDTA plasma banked in the MGB Biobank between Jan 1-Dec 1, 2019 from inpatients. Blinding LFAs were analyzed by blinded operators according to manufacturer instructions for use (IFU), with the exception of using micropipettes instead of manufacturer-provided droppers to minimize technical variability. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
… SciScore for 10.1101/2021.01.02.20248998: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The study was approved under the Massachusetts General Brigham (MGB) Institutional Review Board (protocol no. 2020P001204) Randomization Pre-pandemic negative control samples were randomly selected from healthy participants with a Charlson Age-Comorbidity Index38 score ≤2, with EDTA plasma banked in the MGB Biobank between Jan 1-Dec 1, 2019 from inpatients. Blinding LFAs were analyzed by blinded operators according to manufacturer instructions for use (IFU), with the exception of using micropipettes instead of manufacturer-provided droppers to minimize technical variability. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources Ultrasensitive Simoa Serology Assays: Plasma samples were diluted 4000-fold, and the total IgG and IgM levels against the SARS-CoV2 spike protein were measured using a custom Single Molecule Array (Simoa) assay as described39 on an automated HD-X Analyzer (Quanterix, Billerica, MA, USA), to provide a quantitative reference for anti-spike antibody titers in the plasma samples. total IgGsuggested: Noneanti-spikesuggested: NoneAntibody concentrations were estimated using a calibration curve of recombinant anti-SARS-CoV-2 antibodies40. antibodies40suggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our study presents a few limitations. Although we successfully benchmarked the performance of the LFAs to a quantitative assay39, we did not determine the neutralizing potential of these antibodies. Secondly, samples were acquired when PCR testing was restricted to severely ill patients. For epidemiological studies and population surveillance, it will be important to evaluate assay performance on asymptomatic individuals. In conclusion, our study provides a public resource to aid researchers, healthcare providers, public health professionals, and industries impacted by the pandemic such as airlines, in choosing the appropriate LFAs for their intended use cases.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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