SARS-CoV-2 Antigen Test Results to Infer Active or Non-Active Virus Replication Status in COVID-19 Patients

Abstract

We used nasopharyngeal swab samples of patients with a symptomatic (n = 82) or asymptomatic (n = 20) coronavirus disease 2019 (COVID-19) diagnosis to assess the ability of antigen detection tests to infer active (potentially transmissible) or inactive (potentially non-transmissible) infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using the subgenomic RNA (sgRNA) as an active replication marker of SARS-CoV-2, 48 (76.2%), 56 (88.9%), and 63 (100%) of 63 samples with sgRNA positive results tested positive with the SD BIOSENSOR STANDARD Q COVID-19 Ag (Standard Q), the SD BIOSENSOR STANDARD F COVID-19 Ag FIA (Standard F), or the Fujirebio LUMIPULSE G SARS-CoV-2 Ag (Lumipulse) assay, respectively. Conversely, 37 (94.9%), 29 (74.4%), and 7 (17.9%) of 39 samples with sgRNA negative results tested negative with Standard Q, Standard F, or Lumipulse, respectively. Stratifying results by the number of days of symptoms before testing revealed that most antigen positive/sgRNA positive results were among samples tested at 2–7 days regardless of the assay used. Conversely, most antigen negative/sgRNA negative results were among samples tested at 16–30 days only when Standard Q or Standard F were used. In conclusion, based on our findings, a negative antigen test, especially with the Lumipulse assay, or a positive antigen test, especially with the Standard F assay, may suggest, respectively, the absence or presence of replication-competent SARS-CoV-2.

Clinical Validation of a Colorimetric Loop-Mediated Isothermal Amplification Using a Portable Device for the Rapid Detection of SARS-CoV-2

“…The choice to use the antigen-test solution in 2022 for RT-qPCR was caused by the emergence of the Omicron variant and the second wave of COVID-19 cases. The number of cases rose quickly, and antigen tests were more efficient in detecting individuals with active viral replication [ 31 , 32 ]. In addition, this system would avoid the need for collecting three nasopharyngeal samples from the same person, considering that one sample was already used for RT-LAMP.…”

Point-of-care detection of SARS-CoV-2 antigen among symptomatic vs. asymptomatic persons: Testing for COVID-19 vs. infectivity

“…This finding was confirmed in a recent study, in which Veritor showed a sensitivity of 74% when compared to cell culture ( 25 ). Similarly, a study on the diagnostic performance of different Ag-RGT by contrasting the results with detection of subgenomic RNA suggests their ability to determine the presence or absence of replication-competent, thus potentially transmissible, virus ( 26 ). In order to implement these findings to the clinical practice, one should take into account the role of infectivity.…”

“…Still, testing of asymptomatic individuals is recommended in some settings ( 24 ) and NAAT techniques may not represent an appropriate standard reference in this population as they do not distinguish infectious and non-infectious virus, thus failing to identify persons with non-infectious SARS-CoV-2 infection in whom isolation could be spared. In contrast, recent studies suggest an association between positive Ag-RDT results and cell culture positivity, as well as the presence of subgenomic RNA, a surrogate for the presence of viable virus ( 25 , 26 ).…”