Making sense of rapid antigen testing in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostics

Abstract

Although the most effective strategy for preventing or containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks relies on early diagnosis, the paramount and unprecedented number of tests needed to fully achieve this target is overwhelming worldwide testing supply and capacity. Molecular detection of SARS-CoV-2 RNA in nasopharyngeal swabs is still considered the reference diagnostic approach. Nonetheless, identification of SARS-CoV-2 proteins in upper respiratory tract specimens and/or saliva by means of rapid (antigen) immunoassays is emerging as a promising screening approach. These tests have some advantages compared to molecular analysis, such as point of care availability, no need of skilled personnel and dedicated instrumentation, lower costs and short turnaround time. However, these advantages are counterbalanced by lower diagnostic sensitivity compared to molecular testing, which would only enable to identifying patients with higher SARS-CoV-2 viral load. The evidence accumulated to-date has hence persuaded us to develop a tentative algorithm, which would magnify the potential benefits of rapid antigen testing in SARS-CoV-2 diagnostics.

Evaluation of PCL rapid point of care antigen test for detection of SARS‐CoV‐2 in nasopharyngeal swabs

“…Nonetheless, the results of an Ag-RDT depend on several factors, such as time from the symptom onset, the specimen viral content, and other preanalytical and analytical considerations. 2,4,10,11 In our study, the PCL COVID-19 Ag rapid FIA had a sensitivity 92.9% for CT values under 25, which demonstrated that CT values were crucial to the results of Ag-RDT. Thus, PCL COVID-19 Ag Rapid FIA was more sensitive at high viral loads and therefore its utility may be limited to patients with a recent onset of symptoms, when viral load is very high.…”

“…However, there remains limited evidence on the utility of Ag-RDTs for coronavirus disease 2019 (COVID-19) diagnosis and surveillance, with significant variability reported with respect to their diagnostic performance and a lack of external validation for many of the available tests. 10 Thus, we initiated our study to evaluate an Ag-RDT, the PCL COVID-19 Ag rapid fluorescent immunoassay (FIA), for diagnosis of COVID-19 in hospitalized patients with suspect SARS-CoV-2 infection. The results of this test were compared with qualitative and quantitative results of parallel reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) examinations.…”

“…Nonetheless, the performance of this particular Ag-RDT limits its applicability for both clinical and community testing. While viral loads in patients with presymptomatic or asymptomatic disease are lower as compared to symptomatic patients, thus leading to limited detection of SARS-CoV-2 by Ag-RDTs in such individuals, 10 this may be deemed acceptable, as such a low viral load seemingly correlates to the reported reduced transmission potential among asymptomatic or presymptomatic persons. 12 However, this assay failed to accurately detect SARS-CoV-2 in symptomatic hospitalized patients, raising substantial concerns over its utility.…”

A Prospective Study to Evaluate the Clinical Performance of A Novel MultitargetBased Antigen Test on the Detection of SARS-CoV-2 in Symptomatic PopulationComparison to Nuclear Acid-Based Tests

“…However, although rapid antigen tests generally have a satisfactory specificity (between 90% and 100%), they demonstrated a lower diagnostic sensitivity in comparison to molecular testing, especially with specimens containing low viral loads [7]. The implementation and widespread usage of an antigen test should be verified under well-defined circumstances.…”

The role for pre-operative CT chest scans in suspected COVID-19 patients requiring emergent surgery

“…A recent survey from the American Association of Clinical Chemistry (AACC) has revealed that over 60% of worldwide laboratories are currently reporting to face serious challenges in obtaining sufficient amount of reagents and test kits needed for routine SARS-CoV-2 diagnostics [4]. While newer rapid antigen assays with TAT as short of 15-30 min are now commercially available, they are still not routinely used and have variable sensitivity for detecting SARS-CoV-2 [5]. As such, preoperative CT imaging has been explored as a potential tool for screening patients for SARS-CoV-2 infection [6].…”