A negative COVID RAT result using a validated lateral-flow device is very likely a reliable indicator of being non-infectious.
Early in the COVID pandemic, diagnostic testing relied entirely on precise-but-expensive PCR testing. Late in 2020 the Lateral Flow Testing techniques, already widely used for home-pregnancy tests and similar, were developed for SARS-CoV-2 antigens, leading to COVID-19 Rapid Antigen Tests (RATs).
While cheap, scalable and able to give a result in 10-15 minutes, they were initially seen mostly as a supplement to PCR testing, with less accuracy. Although true that RATs have lower sensitivity than SARS-CoV-2 PCR – most licensed-RATs have sensitivity 80-95% – today this is both less important, and possibly even a strength of RATs over PCR.
Early in the pandemic the role of testing has primarily about diagnosis, in those either symptomatic or pre-symptomatic. Viral presence was practically assumed to be synonymous with contagion. Today with over half a billion cumulative COVID cases worldwide and counting, along with access to effective vaccines and antivirals, it is often more useful to know whether an individual is infectious or not at a discrete moment in time.
Growing research over the last 12 months shows that adequately-sensitive RATs are effective at identifying infectious individuals, even if the high-sensitivity of PCR testing identifies viral particles in those who are infected but otherwise non-infectious (either pre-infectious, or post-infectious with ongoing viral shedding).
PCR positive results with cycle thresholds (ie. number of thermal cycles of RNA replication required before fluorescence is detected) above 25-30 have good correlation with being non-infectious (ie. unable to culture virus). Adequately approved & validated RATs (by FDA, TGA, MHRA, etc.) have very high sensitivity at CT less than this 25-30 range, depending on the study and specific manufacturer.
The bottom line...
An adequately-validated RAT, when correctly performed, is likely a sensitive indictor of individual infectiousness at that specific moment in time. The reliability of a negative RAT will be improved if using the same manufacturer and technique as a RAT previously positive test, and more so if there are several subsequent negative RATs.
Various RATs investigated showed 99% sensitivity in identifying contagious COVID patients (PCR Ct < 30).
"The inoculation of cell cultures with RT-qPCR negative swabs and RT-qPCR positive swabs with ct values >25 did not induce cytopathic effects that were related to SARS-CoV-2."
This study is primarily an evaluation of a specific RAT, the Coris coronavirus disease 2019 Ag Respi-Strip test – which while showing poor sensitivity, it again demonstrates that RAT-positivity correlates with viral load. This study used PCR-detection as the gold standard for evaluation, which because of the extreme sensitivity of PCR testing, does not easily translate to assessment of contagiousness (although Ct > 25-30 seems to correlate with inability to grow in viral culture).
SARS-CoV-2 rapid antigen test positivity correlates well with viral loads typically seen in the infectious period. RATs may be useful tools to discriminate between infectious and non-infectious individuals.
Early 2021 update of the 2020 Cochrane Review: Rapid, point-of-care antigen and molecular-based tests for diagnosis of SARS-CoV-2 infection.
Better data is now available on correlation between PCR cycle threshold and likely infectivity.
Although labelled as 'false' negative, negative RATs associated with positive PCR results, were in this study all in low viral-concentration patients, determined by a high PCR cycle threshold (ie. number of thermal cycles of RNA replication required before fluorescence is detected).
High PCR CT / calculated low-viral-concentration, correlates well with low/non-infectivity of the individual. This does not mean that they may not become infectious in the future, but rather means that at that point in time they are unlikely to be infectious.
Early 2020 studies of COVID rapid antigen tests were of low quality and of variable applicability to COVID diagnostic decisions. This situation improved dramatically in 2021 and 2022, and many RATs are now continually validated in existing and emerging variants.
This Cochrane Review was updated in 2021.
Lateral Flow Devices / RATs show good correlation with low cycle threshold PCR results, and subsequent viral culture, indicating excellent sensitivity for identifying contagious individuals.