Lateral flow COVID tests: Convenient and fast but negative results don't rule out infection

Rapid lateral-flow tests for SARS-CoV-2, the virus causing COVID-19, were widely used during the pandemic to identify infected individuals to guide treatment and reduce onward transmission of the virus. These tests were used in schools and workplaces, prior to travel overseas, to test people wishing to access high-risk individuals in care homes, and to diagnose patients in healthcare settings such as hospitals and general practices.

The most widely used mass testing approach offered through government testing centres in the UK and elsewhere was the so-called ‘PCR’ laboratory test, which identifies the genetic material of the virus if present in a sample taken from a person.

PCR is acknowledged as a very sensitive test, meaning that it is unlikely to miss the virus if present in a sample. Given that there were so many different types of rapid lateral-flow tests available and that they were so widely used, it was very important to understand how well they could identify infected people by comparison with PCR, so that doctors and people working in public health could understand which tests to use and how to use them.

We evaluated the performance of two different rapid tests:

• SD Biosensor Standard™ Q SARS-CoV-2 Rapid Antigen Test (REF 9901-NCOV-01G, branded and distributed by Roche Diagnostics GmbH, Mannheim, Germany) -- just "SD biosensor" for the rest of this post.
• BD Veritor™ System for Rapid Detection of SARS-CoV-2 coupled with the BD Veritor™ Plus Analyzer (REF 256089, Becton Dickinson and Company, Maryland, USA) -- just "BD veritor" for the rest of this post.

Both tests were similar in format to the tests people used at home, though they were 'professional use only' tests, as opposed to the self-tests most will be familiar with. The BD Veritor test also used a small electronic reader to interpret the test. We evaluated these tests between October 2020 and October 2021 in 19 GP surgeries across England and in two testing centres in Wales. Testing was carried out by healthcare staff such as GPs, nurses, or healthcare assistants, and not by laboratory specialists.

In our study, we only included people who had symptoms of COVID-19 as defined by UK’s public health authority, the UK Health Security Agency. There was no restriction on the age of those who could take part in the study. In total 663 people took part in the study. We compared the results of the rapid tests against the results of PCR – samples were taken for both at the same time.

We found that 260 of the 663 (39%) participants in the study tested positive for SARS-CoV-2 by PCR.

The two main factors we measured about each test were the ‘sensitivity’ and the ‘specificity’, two related concepts. The SD Biosensor test had a sensitivity of 84% and a specificity of 98.5% whilst the BD Veritor test had a sensitivity of 76.5% and specificity of 98.8% when compared to the PCR test.

Sensitivity tells us how well a test can identify someone who has a particular condition; in our case SARS-CoV-2. If we use the example of the SD Biosensor in our study, this correctly identified 84% of people who were found by PCR to be infected, and missed 16%.

Specificity, on the other hand, tells us how well a test determines if someone doesn’t have a condition. Using our example of the SD Biosensor test again, this test correctly identified that 98.5% of people who had a negative PCR test were not infected, but incorrectly indicated that 1.5% of people who had a negative PCR test were infected.

Overall, rapid lateral-flow tests are convenient, fast and can be used almost anywhere in a healthcare system as they do not require the complex supportive infrastructure or training of more complex tests.

The high specificity of these tests – how many truly negative samples a test detects – means that a patient with symptoms and a positive result is very likely to have COVID-19, providing that the tests are used at a time when the prevalence is similar to that seen in this study.

However, the moderate sensitivity of these tests – how many truly positive sample a test detects –  means that they should not be used to rule-out infection in symptomatic patients with negative test results, as it is likely that some people with the virus will not be identified by these tests.

(These can be a difficult concept to visualise in reality, especially if the concepts are new, so have a look at the interactive graphic we made for the CONDOR platform here, which should help to explain and visualise the difference. We used this to generate the two figures at the bottom of this post.)

Additionally, our results indicate that both tests were most sensitive within the first 5-6 days after symptoms began in participants, after which sensitivity deteriorated very quickly.

It’s important to note that the findings of this work have some limitations which need to be considered by healthcare professionals who might wish to use these tests in the future.

• The study took place in England and Wales at a time when the so-called Alpha and Delta variants of SARS-CoV-2 dominated and which are no longer in wide circulation following the emergence of the Omicron variant of the virus.
• Although these tests were developed to be as ‘variant-proof’ as possible, there is the potential for these tests to perform better or worse than our estimates for the latest circulating variants of the virus.
• As the study was carried out in people with symptoms of COVID-19, we can also not say how well the tests might perform in people without symptoms.
• The study was carried out over periods when many people had COVID-19 so there was a reasonable chance that someone with symptoms was actually infected.
• Although, these tests did not falsely identify many people as having COVID-19 when they didn’t, under circumstances when infection rates are very low (the prevalence), more people could be falsely diagnosed with COVID-19 than actually have the virus.

The takeaway

There is now a lot of scientific information available about rapid lateral flow-type tests for SARS-CoV-2 and how they work in different groups of people.

Generally speaking if these tests are positive then it is very likely that a person is infected with the virus, but a negative test is unlikely to rule-out infection.

Some scientists have argued that these kinds of tests are very good at identifying people who can pass the virus to others and that people with negative results either aren’t infected or weren’t infectious to others at the time the test was carried out. Further work is probably required to definitively demonstrate that this is the case.

With respect to this work, and the work of other scientists, it seems clear that it is best to test people as soon as possible after they develop symptoms as the tests are likely to work best at this time.

In summary, our evaluation of two rapid tests for SARS-CoV-2 showed that negative results do not preclude the possibility of infection in patients with symptoms, however patients with symptoms and positive test results are almost certainly infected with the virus. These tests should also not be expected to reliably identify infected individuals more than a week after their symptoms begin.

Whilst this study concentrated on tests which aim to support the diagnosis of COVID-19 alone, we have since been focusing on tests which have been developed to identify patients with COVID-19 or influenza, as these tests are potentially more useful to healthcare professionals seeing patients with respiratory illness.

Reference:

Evaluation of the diagnostic accuracy of two point-of-care tests for COVID-19 when used in symptomatic patients in community settings in the UK primary care COVID diagnostic accuracy platform trial (RAPTOR-C19)
Nicholson BD, Turner PJ, Fanshawe TR, Williams AJ, Amirthalingam G, et al. (2023) Evaluation of the diagnostic accuracy of two point-of-care tests for COVID-19 when used in symptomatic patients in community settings in the UK primary care COVID diagnostic accuracy platform trial (RAPTOR-C19). PLOS ONE 18(7): e0288612. https://doi.org/10.1371/journal.pone.0288612

Infographic of summary results

Click to enlarge: An infographic showing the results of the two test evaluated.