ABSTRACT
ObjectivesWe conducted a meta-analysis of RAT diagnostic accuracy for SARS-CoV-2 infections, and further evaluated test sensitivity versus the presence of symptoms, days post symptom onset (DPSO), sample viral load, and sample type (i.e. direct swabs versus specimens stored in transport media). MethodsThree databases were searched systematically for performance evaluations of the Roche-distributed SDB SARS-CoV-2 Rapid Antigen Test (Roche/SDB RAT) through March 2022. If the Roche/SDB RAT was compared with any of 9 commonly available antigen tests, data from these tests were also included. ResultsOverall sensitivity of RATs among different manufacturers and study cohorts varied between 36.0% (95% CI: 24.0-50.1) and 79.4% (95% CI: 64.8-89.0). Roche/SDB RATs demonstrated a competitive performance with a pooled (including off-label use) sensitivity of 70.0%, and nearly 100% specificity in included studies. The Roche/SDB RATs exhibited reliable sensitivity in patients with a relatively high viral load (96.6% [95% CI: 95.2-98.2] for Ct[≤]25). Roche/SDB RATs were more sensitive in symptomatic patients within the first 7 DPSO (85.5% [95% CI: 81.2-88.4]), and when used to test direct swabs (74.4% [95% CI: 69.7-80.3]). ConclusionRATs show reliable performance in clinical settings and should be considered when rapid diagnosis of SARS-CoV-2 infection is critical. HIGHLIGHTSO_LIMeta-analysis of 86 studies of SARS-CoV-2 rapid antigen test (RAT) performance C_LIO_LIRAT performance supports near-patient testing for early COVID-19 diagnosis C_LIO_LIRAT specificity is high and sensitivity is reliable in those with high viral load C_LIO_LIRAT sensitivity in symptomatic patients is higher than in asymptomatic individuals C_LIO_LIRAT sensitivity is higher for direct swabs compared to swabs in transport media C_LI
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
Objective The study aimed to establish the performance of the SARS-CoV-2 Rapid Antibody Test (IgG and IgM) and the Elecsys(R) Anti-SARS-CoV-2 S assay in vaccinated individuals. Methods A panel of serum samples from Boca Biolistics was utilized to assess antibodies following vaccination, consisting of samples drawn prior to vaccination, after the first dose, or at least 14 days after the second dose of Moderna mRNA-1273 or Pfizer-BioNTech BNT162b2 COVID-19 vaccines. Agreement between the two methods was measured and stratified by test evaluator and assay lot. Results Agreement between the SARS-CoV-2 Rapid Antibody Test (IgG) and Elecsys Anti-SARS-CoV-2 S assay qualitative measurements at the different assessment points for both mRNA-1273 and BNT162b2 ranged between 97.06% (95% confidence interval [CI] 84.67, 99.93) to 100% (95% CI 82.35, 100). Agreement of the SARS-CoV-2 Rapid Antibody Test (IgG) with the Elecsys Anti-SARS-CoV-2 S assay was not highly influenced by either lot or evaluator. There was a medium-to-strong correlation between the semi-quantitative SARS-CoV-2 Rapid Antibody Test (IgG) result and quantitative Elecsys Anti-SARS-CoV-2 S assay in samples taken after both doses of the vaccines, with higher intensity bands being associated with higher total anti-S antibody titer (mRNA-1273, p=0.0019; BNT162b2, p<0.0001). Conclusion Semi-quantitative SARS-CoV-2 Rapid Antibody Test (IgG) and quantitative Elecsys Anti-SARS-CoV-2 S assay correlated well, suggesting that the SARS-CoV-2 Rapid Antibody Test (IgG) is helpful in understanding the immune response post-vaccination. The current data support the use of the SARS-CoV-2 Rapid Antibody Test (IgG) in the vaccinated population.
Subject(s)
COVID-19ABSTRACT
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(R), 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.
Subject(s)
COVID-19ABSTRACT
The true prevalence and population seropositivity of SARS-CoV-2 infection remains unknown, due to the number of asymptomatic infections and limited access to high-performance antibody tests. To control the COVID-19 pandemic it is crucial to understand the true seroprevalence, but not every region has access to extensive centralized PCR and serology testing. Currently available rapid antibody tests lack the accuracy needed for recommendation by health authorities. To fill this gap, we analyzed and validated the clinical performance of a new point-of-care SARS-CoV-2 Rapid Antibody Assay, a chromatographic immunoassay for qualitative detection of IgM/IgG antibodies for use in near-patient settings. Analysis was performed using 42 Anti-SARS-Cov-2 positive (CoV+) and 92 Anti-SARS-Covid-2 negative (CoV-) leftover samples from before December 2019, using the Elecsys(R) Anti-SARS-CoV-2 as the reference assay. Analytical specificity was tested using leftover samples from individuals with symptoms of common cold collected before December 2019. The SARS-CoV-2 Rapid Antibody Test was 100.0% (95% CI 91.59-100.00) sensitive and 96.74% (95% CI 90.77-99.32) specific with an assay failure rate of 0.00%. No cross-reactivity was observed against the common cold panel. Method comparison was additionally conducted by two external laboratories, using 100 CoV+/275 CoV-samples, also comparing whole blood versus plasma matrix. The comparison demonstrated for plasma 96.00% positive/96.36% negative percent agreement with the Elecsys Anti-SARS-CoV-2 and overall 99.20% percent agreement between whole blood and EDTA plasma. The SARS-CoV-2 Rapid Antibody Test demonstrated similar clinical performance to the manufacturer's data and to a centralized automated immunoassay, with no cross-reactivity to common cold panels.