Comparing the diagnostic accuracy of rapid antigen detection tests to real time polymerase chain reaction in the diagnosis of SARS-CoV-2 infection: A systematic review and meta-analysis

Abstract

Background Timely and accurate diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is crucial to reduce the risk of viral transmission. We investigated the diagnostic accuracy of rapid antigen detection tests (RADTs) in the diagnosis of SARS-CoV-2 infection. Methods A systematic literature search was performed using Pubmed, Embase, and the Cochrane Central Register. The sensitivity, specificity, diagnostic odds ratio (DOR), and a hierarchical summary receiver-operating characteristic curve (HSROC) of RADTs were pooled using meta-analysis. We used commercial and laboratory-developed reverse transcriptase-polymerase chain reaction (RT-PCR) as reference standards. Results We identified 24 studies comprising 14,188 patients. The overall pooled sensitivity, specificity, and DOR of RADTs for diagnosis of SARS-CoV-2 were 0.68 (95%CI, 0.59 to 0.76), 0.99 (95%CI, 0.99 to 1.00), and 426.70 (95% CI, 168.37 to 1081.65), respectively. RADTs and RT-PCR had moderate agreement with an estimated pooled Cohen's kappa statistic of 0.75 (95%CI, 0.74-0.77), and area under the HSROC of 0.98 (95%CI, 0.96 to 0.99). The pooled sensitivity of RADTs was significantly increased in subjects with viral load of Ct-value ≤25 or in those within 5 days after symptom onset than it was in subjects with lower viral loads or longer symptom duration. Conclusions The overall sensitivity of RADTs was inferior to that of the RT-PCR assay. The RADTs were more sensitive for samples of Ct-value ≤25 and might be suitable for subjects in the community within 5 days of symptom onset.

Accuracy of Roche SARS-CoV-2 Rapid Antigen Test in Nasopharyngeal Swab: Clinical Impression Matters

“…Krüttgen, et al [13] reported that the sensitivity was 95% or higher in samples with Ct < 30, but then decreased to 45% and 22% in those with Ct between 30-35 and > 35, respectively. In metaanalysis on RAT by Lee, et al [14], sensitivity increased with low Ct value. In present study the sensitivity increased to 78% in the case of a high viral load; thus, supporting previous reports [7,12].…”

“…The same sensitivity results with diff erent brand of RAT were recorded in Pakistan[4] and French[11]; therefore, not all available SARS-CoV-2 RAT had a sensitivity of ≥ 80 -90%. Therefore, they suggested a confi rmatory RT-PCR test in cases with negative RAT.The explanations on variation in sensitivity of RAT were interesting: (1) viral load[7,[12][13][14]; (2) unsuffi cient amount of viral protein in nasopharyngeal swab[15]; (3) presence or absence of symptom[7,14,16]; (4) symptom onset days (sample collection timing in relation to symptoms)[5,7,14];(5) skills of the operator in taking nasopharyngeal swab and doing RAT[15,17];(6) quality of storage of nasopharyngeal swab sample particularly viral transport media; (7) handling of swab [18]; (8) cross contamination; (9) cross reaction with drugs and chemicals; (10) hook eff ect; (11) viral mutation;…”

Rapid Antigen Test Combine with Nucleic Acid Detection: A Better Strategy for COVID-19 Screening at Points of Entry

“…In the context of emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, increasing the number of tests during the quarantine period, shortening the regular testing period for staff with a high risk of exposure at airports, and identifying COVID-19 patients as early as possible through rapid screening may aid the control of the epidemic at border entry. The current standard for detection of SARS-CoV-2 is NAAT such as reverse transcriptase polymerase chain reaction (RT-PCR) [ 1 ]. RT-PCR tests have high accuracy, but it has high requirements for testing equipment and operators, and is expensive and time-consuming (most would take 1–3 days).…”

“…On the other hand, rapid antigen tests (RAT) most only take 15–30 min to obtain test results and are simple and inexpensive [ 1 ]. Unlike RT-PCR, the antigens need not be multiplied to sufficient levels for the test to detect the virus.…”

“…If the viral load in the sample is low, the test can be negative. The pooled sensitivity and pooled specificity of Standard Q COVID-19 Ag test, a RAT in the emergency use listing that was recommended by the WHO, were 0.83 (95% CI 0.63–0.94) and 0.99 (95%CI, 0.95–1.00), respectively [ 1 ]. Previous studies showed that STANDARD F COVID-19 Ag FIA is highly specific (98.4%, 95% CI 96.0–99.6%) for SARS–CoV-2 Ag detection in NPS, and highly sensitive (95.2%, 95% CI 76.2–99.9%) for samples with cycle threshold (Ct) value lower than 25 [ 2 – 4 ].…”