Clinical Characterisation of Lateral Flow Assays for Detection of COVID-19 Antibodies in a population

ImportanceSerological assays can help diagnose and determine the rate of SARS-CoV-2 infections in a population. ObjectiveWe characterized and compared 11 different lateral flow assays for their performance in diagnostic or epidemiological settings. Design, Setting, ParticipantsWe used two cohorts to determine the specificity: (i) up to 350 blood donor samples from past influenza seasons and (ii) up to 110 samples which tested PCR negative for SARS-CoV-2 during the first wave of SARS-CoV-2 infections in Switzerland. The sensitivity was determined using up to 370 samples which tested PCR positive for SARS-CoV-2 during the same time and is representative for age distribution and severity. Main OutcomeWe found a single test usable for epidemiological studies in the current low-prevalence setting, all other tests showed lacking sensitivity or specificity for a usage in either epidemiological or diagnostic setting. However, orthogonal testing by combining two tests without common cross-reactivities makes testing in a low-prevalence setting feasible. ResultsNine out of the eleven tests showed specificities below 99%, only five of eleven tests showed sensitivities comparable to established ELISAs, and only one fulfilled both criteria. Contrary to previous results from lab assays, five tests measured an IgM response in >80% of the samples. We found no common cross-reactivities, which allows orthogonal testing schemes for five tests of sufficient sensitivities. Conclusions and RelevanceThis study emphasizes the need for large and diverse negative cohorts when determining specificities, and for diverse and representative positive samples when determining sensitivities of lateral flow assays for SARS-CoV-2 infections. Failure to adhere to statistically relevant sample sizes or cohorts exclusively made up of hospitalised patients fails to accurately capture the performance of these assays in epidemiological settings. Our results allow a rational choice between tests for different use cases.

Initial characterisation of ELISA assays and the immune response of the clinically correlated SARS-CoV-2 biobank SERO-BL-COVID-19 collected during the pandemic onset in Switzerland

BackgroundTo accurately measure seroprevalance in the population, both the expected immune response as well as the assay performances have to be well characterised. Here, we describe the collection and initial characterisation of a blood and saliva biobank obtained after the initial peak of the SARS-CoV-2 pandemic in Switzerland. MethodsTwo laboratory ELISAs measuring IgA & IgG (Euroimmun), and IgM & IgG (Epitope Diagnostics) were used to characterise the biobank collected from 349 re- and convalescent patients from the canton of Basel-Landschaft. FindingsThe antibody response in terms of recognized epitopes is diverse, especially in oligosymptomatic patients, while the average strength of the antibody response of the population does correlate with the severity of the disease at each time point. InterpretationThe diverse immune response presents a challenge when conducting epidemiological studies as the used assays only detect[~] 90% of the oligosymptomatic cases. This problem cannot be rectified by using more sensitive assay setting as they concomitantly reduce specificity. FundingFunding was obtained from the "Amt fur Gesundheit" of the canton Basel-Landschaft, Switzerland.