Sensitivity of Rapid Antigen Testing and RT-PCR Performed on Nasopharyngeal Swabs versus Saliva Samples in COVID-19 Hospitalized Patients: Results of a Prospective Comparative Trial (RESTART)

Abstract

Saliva sampling could serve as an alternative non-invasive sample for SARS-CoV-2 diagnosis while rapid antigen tests (RATs) might help to mitigate the shortage of reagents sporadically encountered with RT-PCR. Thus, in the RESTART study we compared antigen and RT-PCR testing methods on nasopharyngeal (NP) swabs and salivary samples. We conducted a prospective observational study among COVID-19 hospitalized patients between 10 December 2020 and 1 February 2021. Paired saliva and NP samples were investigated by RT-PCR (Cobas 6800, Roche-Switzerland, Basel, Switzerland) and by two rapid antigen tests: One Step Immunoassay Exdia® COVID-19 Ag (Precision Biosensor, Daejeon, Korea) and Standard Q® COVID-19 Rapid Antigen Test (Roche-Switzerland). A total of 58 paired NP-saliva specimens were collected. A total of 32 of 58 (55%) patients were hospitalized in the intensive care unit, and the median duration of symptoms was 11 days (IQR 5-19). NP and salivary RT-PCR exhibited sensitivity of 98% and 69% respectively, whereas the specificity of these RT-PCRs assays was 100%. The NP RATs exhibited much lower diagnostic performance, with sensitivities of 35% and 41% for the Standard Q® and Exdia® assays, respectively, when a wet-swab approach was used (i.e., when the swab was diluted in the viral transport medium (VTM) before testing). The sensitivity of the dry-swab approach was slightly better (47%). These antigen tests exhibited very low sensitivity (4% and 8%) when applied to salivary swabs. Nasopharyngeal RT-PCR is the most accurate test for COVID-19 diagnosis in hospitalized patients. RT-PCR on salivary samples may be used when nasopharyngeal swabs are contraindicated. RATs are not appropriate for hospitalized patients.

Screening for SARS-CoV-2 in close contacts of individuals with confirmed infection: performance and operational considerations

“…The saliva antigen test had the lowest overall performance, consistent with the findings of other evaluations of POC saliva antigen tests [36,37]. One recent evaluation of this test reported an overall sensitivity of 66.1%; however, the reference assay was conducted on saliva [38].…”

Anti-SARS-CoV-2 Titers Predict the Severity of COVID-19

“…The role of SARS-CoV-2 serological testing for the diagnosis of COVID-19 is currently limited, aside from seroprevalence studies, to specific situations such as in the case of late immune complications of the disease (e.g., multisystem inflammatory syndrome in children or meningoencephalitis) [ 33 , 34 , 35 , 36 , 37 ]. While nucleic acid amplification tests (NAAT) remain the gold standard for COVID-19 diagnosis [ 35 , 38 ], their sensitivity decreases beyond the first week of symptoms, while serology achieves a >90% sensitivity beyond the third week [ 32 , 39 , 40 ]. While patients with complicated COVID-19 usually require hospitalization beyond one week of symptom onset (i.e., median 10 days in the present study), serological testing may be combined to NAAT at hospital admission to increase the diagnostic performance for patients who have >10 days of symptoms and have not been tested during the early phase of the disease.…”

Sensitivity and Specificity of SARS-CoV-2 Rapid Antigen Detection Tests Using Oral, Anterior Nasal, and Nasopharyngeal Swabs: a Diagnostic Accuracy Study

“…Rapid antigen detection (RAD) tests are highly valued in the detection of potentially infectious patients, as they can provide prompt results in a cost-effective manner ( 1 , 2 ). However, in terms of sensitivity, RAD tests are inferior to PCR, and test results are highly dependent on the swabbing method ( 3 ).…”