Longitudinal Assessment of Diagnostic Test Performance Over the Course of Acute SARS-CoV-2 Infection

Abstract

Background Serial screening is critical for restricting spread of SARS-CoV-2 by facilitating the timely identification of infected individuals to interrupt transmission chains. The variation in sensitivity of different diagnostic tests at different stages of infection has not been well documented. Methods This is a longitudinal study of 43 adults newly infected with SARS-CoV-2. All participants provided daily samples for saliva and nasal swab RTqPCR, Quidel SARS Sofia antigen FIA, and live virus culture. Results We show that both RTqPCR and the Quidel SARS Sofia antigen FIA peak in sensitivity during the period in which live virus is detected in nasal swabs, but the sensitivity of RTqPCR tests rises more rapidly prior to this period. We also estimate the sensitivities of RTqPCR and antigen tests as a function of testing frequency. Conclusions RTqPCR tests are more effective than antigen tests at identifying infected individuals prior to or early during the infectious period and thus for minimizing forward transmission (given timely results reporting). All tests showed >98% sensitivity for identifying infected individuals if used at least every three days. Daily screening using antigen tests can achieve ~90% sensitivity for identifying infected individuals while they are viral culture positive.

Longitudinal analysis of SARS-CoV-2 vaccine breakthrough infections reveal limited infectious virus shedding and restricted tissue distribution

“…Finally, we examined the relationship between viral culture and antigen FIA results in vaccinated (fully plus partially) and newly vaccinated individuals (Fig 1G) . We observed that vaccinated and newly vaccinated participants tested positive by antigen FIA on 78% and 85% of the days on which they also tested positive by viral culture, suggesting that antigen FIA can be used to identify vaccine breakthrough infections with high transmission risk, especially if used as part of a serial screening program 9 . These results are consistent with our previous results in unvaccinated individuals as well as earlier cross-sectional studies examining the relationship between antigen tests positivity and infectious virus shedding 7,10,11 .…”

Use cases for COVID-19 screening and surveillance with rapid antigen-detecting tests: a systematic review

“…Four surveillance studies were conducted in Greece, Switzerland, USA, and the Netherlands, which used Ag-RDTs to monitor COVID-19 across an entire town, primary and secondary schoolchildren and teachers, university students and staff, and in professional football clubs, respectively. 41-44…”

Viral loads observed under competing strain dynamics

“…Accounting for time-since-onset is therefore advisable regardless. Other instances where epidemic dynamics will not affect viral load comparisons are when samples are obtained longitudinally from the same individuals, allowing the comparison of the full viral kinetics curve [20,35], or obtained near the time of exposure such that all samples have a similar time-since-infection [36].…”