Longitudinal assessment of diagnostic test performance over the course of acute SARS-CoV-2 infection

Abstract

What is already known about this topic? Diagnostic tests and sample types for SARS-CoV-2 vary in sensitivity across the infection period. What is added by this report? We show that both RTqPCR (from nasal swab and saliva) and the Quidel SARS Sofia FIA rapid antigen tests peak in sensitivity during the period in which live virus can be detected in nasal swabs, but that the sensitivity of RTqPCR tests rises more rapidly in the pre-infectious period. We also use empirical data to estimate the sensitivities of RTqPCR and antigen tests as a function of testing frequency. What are the implications for public health practice? RTqPCR tests will be more effective than rapid antigen tests at identifying infected individuals prior to or early during the infectious period and thus for minimizing forward transmission (provided results reporting is timely). All modalities, including rapid antigen tests, showed >94% sensitivity to detect infection if used at least twice per week. Regular surveillance/screening using rapid antigen tests 2-3 times per week can be an effective strategy to achieve high sensitivity (>95%) for identifying infected individuals.

Concordance between PCR-based extraction-free saliva and nasopharyngeal swabs for SARS-CoV-2 testing

“…As expected, the positive agreement between the first diagnosis and the saliva or repeat NPS decreased over time, reflecting recovery and viral clearance. These findings are consistent with other longitudinal studies of COVID-19 testing ( Smith et al , 2021 ; Wyllie et al , 2020 ). However, our results are the first to show that the drop in performance is consistent across saliva and NPS, thereby showing once again that the SalivaDirect accuracy is very similar to the gold-standard RT-qPCR from NPS.…”

“…Testing for SARS-CoV-2 in saliva mitigates many of the challenges associated with NPS sampling (Tan et al, 2021;Vaz et al, 2020;Wyllie et al, 2020). Although various different protocols for SARS-CoV-2 testing in saliva have been proposed, including colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) and lateral flow assays (Faustini et al, 2020;Lalli et al, 2021), RT-qPCR is the most common used modality (Caulley et al, 2021;Migueres et al, 2020;Teo et al, 2021) with a reported sensitivity between ~ 69 to 100% (Azzi et al, 2020;Kojima et al, 2020;Pasomsub et al, 2021;Skolimowska et al, 2020;.…”

Quantitative SARS-CoV-2 viral-load curves in paired saliva and nasal swabs inform appropriate respiratory sampling site and analytical test sensitivity required for earliest viral detection

“…Initial data by us 12 and others 13-15 show that, at least in some humans, SARS-CoV-2 viral load can be low (in the range of 10 3 −10 5 copies per mL of saliva sample) early in infection and therefore high-sensitivity tests would be required to reliably detect infection. However, most previous studies to date have focused only on viral detection, not viral-load quantification.…”

Comparison of antigen- and RT-PCR-based testing strategies for detection of SARS-CoV-2 in two high-exposure settings

“…During the COVID-19 pandemic, RT-PCR testing has been established as the standard by which to measure other tests. Our modeling analysis demonstrates that using viral culture, which may better reflect viral transmissibility [ 8 , 9 ], as the test standard dramatically alters the relative performance of different surveillance testing strategies. Under this paradigm, antigen-based surveillance testing strategies coupled with infectious case isolation are shown to strongly reduce disease burden at a level close to RT-PCR-based strategies, but at a much lower economic cost (Figs 2 and 3 ), somewhat in contrast to model results under a more typical RT-PCR test-standard paradigm (S2 Fig in S1 File ).…”

“…However, it has been suggested that when comparing antigen- and RT-PCR tests to viral culture, a proxy for transmissibility, one rapid antigen test (Becton Dickinson Veritor) had a negative percent agreement of 96.4% (95% CI: 82.3, 99.4) and a positive percent agreement of 90.0% (CI: 76.3, 97.6), while positive percent agreement for the RT-PCR assay was 73.7% (CI: 60.8, 85.3) [ 8 ]. Another study found that a different rapid antigen test (Quidel SARS Sofia FIA) reported results that reflected viral culture to a similar degree as results of RT-PCR tests during the infectious period, though RT-PCR tests performed better at identifying future or past infectiousness [ 9 ]. If confirmed through further study, these findings suggest that antigen tests may perform better than RT-PCR tests at discriminating actively infectious infections, complimenting reports showing that RT-PCR tests detect low levels of viral nucleic acid that may not indicate current infectiousness [ 10 , 11 ].…”