Real-world clinical performance of commercial SARS-CoV-2 rapid antigen tests in suspected COVID-19: A systematic meta-analysis of available data as of November 20, 2020

BackgroundImmunochromatographic rapid antigen tests (RATs) emerged onto the COVID-19 pandemic testing landscape to aid in the rapid diagnosis of people with suspected SARS-CoV-2 infection. RATs are particularly useful where RT-PCR is not immediately available and symptoms suggestive of a high viral load and infectiousness are assumed. Several lateral flow immunoassays have been authorized for use under EUA and/or the CE mark, presenting varying overall clinical performance data generated by the manufacturer or by independent investigators. To compare the real-world clinical performance of commercially available rapid chromatographic immunoassays intended for the qualitative detection of SARS-CoV-2, we performed a systematic meta-analysis of published data.MethodsWe searched the MEDLINE®, Embase, BIOSIS and Derwent Drug File (ProQuest)for manufacturer-independent prospective clinical performance studies comparing SARS-CoV-2 RATs and RT-PCR assays. Only studies on lateral flow assays not needing a separate reader for retrieving the result were included, if data were available on viral load, patients’ symptom status, sample type, and PCR assay used. For better data comparability, recalculation of the studies’ single performance data confidence intervals using the exact Clopper–Pearson method was applied.ResultsWe could include 19 studies (ten peer-reviewed) presenting detailed clinical performance data on 11,209 samples with 2449 RT-PCR-positives out of study prevalence rates between 1.9–100 % and between 50– 100% symptomatic samples. Four studies directly compared two to three different RATs and 15 studies compared one RAT to RT-PCR. Overall specificity ranged, with one test outlier, between 92.4% (87.4– 95.9) and 100% (99.7–100), and overall clinical sensitivity varied between 28.9% (16.4–44.3) and 98.3% (91.1–99.7), depending on assay, population characteristics, viral load, and symptom status. Sensitivity in high-viral-load samples (cycle threshold ≤25) showed a considerable heterogeneity among the assays ranging from 66.7% to 100%.ConclusionOnly two RATs offered sufficient manufacturer-independent, real-world performance data supporting use for the detection of current SARS-CoV-2 infection in symptomatic or high-viral-load patient populations. Reliable positive predictive values require testing of symptomatic patients or asymptomatic individuals only in case of a high pre-test probability. If RATs are used for screening of asymptomatic cases in low-prevalence scenarios, a lower positive predictive value of the result has to be considered.