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A preprint, an unpublished non-peer reviewed study, describes the discordance in saliva SARS-CoV-2 PCR and nasal lateral flow antigen test results during the early infectious period.
Dr Julian Tang, Honorary Associate Professor/Clinical Virologist, Respiratory Sciences, University of Leicester, said:
“This is a small study that uses the same TaqPath PCR assay (with SGTF) that are used in the UK lighthouse (Pillar 2) labs, and two (Quidel QuickVue, Abbot BinaxNOW) lateral flow tests – which are different from the NHS lateral flow tests (Innova) used in the UK.
“It shows what we expect for all lateral flow antigen tests – that the more sensitive PCR tests detect SARS-COV-2 earlier and for longer than such lateral flow tests.
“So, people may be shedding and transmitting the virus even if the lateral flow test is negative – either very early in the infection, or late in the infection as the viral loads are rising or falling.
“Now, with a mostly vaccinated population and a clinically milder omicron variant, this may have less clinical impact in terms of hospitalisations and more severe disease.
“But if applied to travellers, only using lateral flow tests may delay the detection of a milder new variant that remains mostly in the community, where samples are no longer routinely sent for sequencing.
“Only if community PCR testing is done, and/or when more severe cases are sent to hospital – where PCR testing and sequencing is routine – will any new variant then be detected.
“Does this matter? Depends on your viewpoint.
“If the new variant is mild then delayed testing may not impact too much because (as with omicron now) most people seem to be happy living with fewer restrictions – and accepting higher case numbers – with only a gradual rise is hospitalisations.
“If the new variant is more severe, then we will see earlier hospitalisations, when we will detect the new variant fairly quickly through sequencing.
“So, the reduced numbers of lateral flow test positive samples that are sent for sequencing may reduce the sensitivity of our community surveillance for new variants – more so for variants that cause milder disease – which do not require hospitalisation.
“But if infections with such variants do not require hospitalisation – just like our usual seasonal common cold coronaviruses – it may not matter too much.”
Dr Alexander Edwards, Associate Professor in Biomedical Technology, Reading School of Pharmacy, University of Reading, said:
“This interesting and important data shows quite how hard it is to work out exactly the best way to use tests, and reminds us why lateral flow tests cannot “rule out” someone being infected, so should not be used to “prove” you are “safe”. This preprint needs peer review and detailed analysis to combine these findings with many other studies to further build our understanding of the typical course of covid-19 infection, especially as this does appear to be somewhat different with the omicron variant.
Overall
“There is clear evidence here showing that lateral flow tests can miss detection early during an infection. This is as expected, because it’s very clear that PCR can detect lower levels of virus than lateral flow rapid tests, and so PCR can pick up cases very early in an infection. Importantly, in this study the amount of virus detected early on is not “really low levels- nothing to worry about” but the research team suggest they have identified evidence that at least some of these cases are infectious – i.e. they have transmitted the virus to someone else. But although this is important and high quality data, it’s incredibly hard to do these important studies, and can also be hard to generalise with these studies that take place in a specific scenario to other settings. For example, risk of transmission will be different depending on the environment (ventilation, how close people are for how long, face coverings, vaccination status, etc etc). Thus we should try not to draw a single hard, conclusive picture of the “typical covid infection” from these studies, for several reasons:
“Thus, although the data is important and notable, we can’t jump to new conclusions about how different tests work.
Saliva vs nasal swab:
“Even if there is more virus in saliva than nasal swabs early in an infection, it’s important to note: you can’t just change the way you take a swab sample for a lateral flow product – if you change the way a test is performed, the manufacturer would have to:
“If a product is changed without proper process, it’s unlikely the modified product would comply with regulations.
“In a research study like this paper, it’s OK to test different samples in the lab. A diagnostic laboratory can modify their process and make sure they document this correctly, to ensure they are regulatory compliant. But home tests have to be really robust and it’s not OK to just change the way they are tested without following rigorous processes.
Conclusions
“What should we do? Keep using lateral flow tests as a tool to try to pick up infections wherever possible, and thereby reduce risk, but not rely too heavily on something that was never designed or manufactured to be able to “rule-out” an infection. Try not to over-use or waste lateral flow tests – use them when they are most needed, and follow guidelines as well as you can. Remember you can be negative by lateral flow, even if you are infected. PCR itself is not perfect, and will miss a proportion of cases. The accuracy of any test will vary depending on who you test, how you exactly perform the test, and so we should be pragmatic and make the best use we can.”
Dr Richard Tedder, member of the Clinical Virology Network, said:
“This is an excellent study based on experience of comparing PCR detection (variously saliva and nasal sources) vs antigen detection in the important real-time setting of managing patients in a hospital environment. It shows, particularly for Omicron, the delay in antigen-based diagnosis of infection using lateral flow against molecular tests based on PCR. The inference is that basing testing on lateral flow assays may allow a period of up to 3 days of viral shedding at levels predicted to be infectious. The inference is that where we are now dealing with an infection where symptoms are preceded by viral shedding, use of lateral flow assays for defining the absence of viral infection and hence absence of infectivity is flawed and in this study such an approach also allows transmissions. This may reflect a different time course of viral shedding in persons infected with Omicron and also an overall increased ease with which Omicron infects a person. Nevertheless it serves to show graphically the lack of sensitivity of the antigen detection approach compared with PCR in the hospital setting.”
Preprint title: ‘Discordant SARS-CoV-2 PCR and Rapid Antigen Test Results When Infectious: A December 2021 Occupational Case Series’ by Blythe J Adamson et al. This work is not peer-reviewed.
https://www.medrxiv.org/content/10.1101/2022.01.04.22268770v1
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www.sciencemediacentre.org/tag/covid-19
Declared interests
None received.