In this blog for anyone interested in LFTs (lateral flow tests, also called rapid antigen tests) for diagnosing COVID-19 infection, Jac Dinnes from University of Birmingham discusses the latest evidence in her Cochrane Review and what it tells us about the accuracy of these tests.
Page originally published: 1 April 2021. Revised and republished 05 August 2022 to reflect the latest Cochrane evidence.
Tests for diagnosing COVID-19 infection are an important tool to help reduce the spread of infection in our communities, schools and workplaces. The use of lateral flow tests or LFTs (also known as antigen detecting rapid diagnostic tests or Ag-RDTs) has become almost commonplace during the COIVD-19 pandemic, having been adopted internationally and often provided free at the point of use. There are many circumstances in which LFTs can be used and it is important to measure how accurately they can detect COVID-19 infection when they are used for different purposes and in different groups of people.
Why have lateral flow tests been so widely adopted?
Lateral flow tests use swab samples taken from the nose or throat, and typically provide results in 20 to 30 minutes. PCR tests use the same swab samples but require specialist laboratory equipment and can take as long as 24 hours to provide a result. LFTs are less expensive than laboratory-based tests and can be used in almost any setting, including in the home, at community COVID-19 test centres, schools, workplaces and healthcare settings.
The rapid and affordable nature of LFTs makes them an attractive option for faster diagnosis of COVID-19, offering the potential for people with positive results to self-isolate and inform close contacts more quickly, with the aim of reducing the spread of infection. The accessibility of LFTs has also led to the introduction of LFT-based policies to allow ‘early’ release from self-isolation for those with confirmed infection and latterly, to allow contacts of confirmed cases to avoid isolation unless they have a positive LFT result. On a population level, LFTs have been used to allow access to healthcare facilities, schools or universities to remain open, mass public gatherings to be held and as part of international travel requirements.
We wanted to know whether commercially produced, rapid point-of-care antigen tests are accurate enough to diagnose COVID-19 infection reliably, and to find out if accuracy varies when LFTs are used in different groups of people and for varying purposes.
What is the volume and quality of the evidence for LFTs?
We updated our Cochrane Review Rapid, point‐of‐care antigen tests for diagnosis of SARS-CoV-2 infection for the second time in July 2022. We included 155 studies evaluating 49 different LFTs produced by commercial test manufacturers available up to 8 March 2021. The main results are based on 152 studies investigating a total of 100,462 nose or throat samples, including 16,822 with COVID-19 infection confirmed by a PCR test.
With each update of this review, we have seen improvements in study quality. Studies used generally relatively rigorous methods, particularly for selecting participants and performing the tests. Importantly however, we could not always identify how long study participants had experienced symptoms of COVID-19, or even whether or not they had symptoms. LFTs were often interpreted without knowing the result of the PCR test (so the PCR result could not have influenced whether the test was judged to be positive or negative). However, the tests were not always done in the way that the test manufacturers recommend. This means that different results might be seen when the tests are used in practice.
How accurate are LFTs when used in people with symptoms of COVID-19?
In people with COVID-19 infection (with positive PCR results), LFTs correctly identified infection in an average of 73% of people with symptoms (test sensitivity). Sensitivity was higher when tests were used in the first week after symptoms first developed (detecting an average of 81% of cases) compared to when they were used later (detecting 49% of confirmed cases). This is likely to be because people have the most virus in their system in the first days after they are infected.
In people who did not have COVID-19 (had negative results on PCR tests), LFTs correctly ruled out infection in 99.1% of people with symptoms.
How accurate are LFTs when used in people with no symptoms of COVID-19?
In people with COVID-19 infection, LFTs correctly identified the infection in an average of 55% of people with no symptoms (18% less than in people with symptoms). Sensitivity was higher when LFTs were only available to people who had been in contact with someone with confirmed COVID-9 infection (an average of 64% of confirmed cases detected by the LFT) compared to when tests were more widely available to anyone who wanted a test (average of 50% of confirmed cases detected by the LFT). This is likely to be because people who can identify a recent contact with a confirmed case are more likely to have become infected and then to have enough virus in their system to be detected by the LFT.
In people who did not have COVID-19 (had negative results on PCR tests), LFTs correctly ruled out infection in 99.5% of people without symptoms.
What do we know about other factors that can affect the accuracy of LFTs?
Accuracy varied when LFTs were used in different settings, for example at COVID-19 test centres, different healthcare settings, in schools or universities, or for screening purposes. This variation in accuracy is likely related to the level of risk of having been in contact with someone with COVID-19 infection and the time since any exposure or since symptoms started.
More evidence is needed to identify how much the type of sample used can affect accuracy, for example using the nasal cavity alone, sampling deeper into the nose or from both the nose and throat. Similarly, accuracy seems to vary between age groups (sensitivity being lower in children compared to adults) but more evidence is needed.
Different brands of tests varied in accuracy, although relatively few studies directly compared one test brand with another. Summary results for only seven tests met World Health Organization (WHO) standards as ‘acceptable’ for confirming and ruling out COVID-19 in people with signs and symptoms of COVID-19. Two more tests met the WHO acceptable standard in one study each. No test met this standard when evaluated in people without symptoms.
Possible benefits and harms from using LFTs
The potential benefits from LFTs have to be balanced against their possible harms, both from missing true cases of infection (false negative results) and from positive test results in people who are not infected (false positives). Negative LFT results in people who have COVID-19 could lead to increased transmission of infection, especially if the negative result encourages them to be less strict about social distancing and other infection control measures. Positive LFT results in people who do not have COVID-19 may lead to unnecessary self-isolation (including time off school or work) for the individual and their close contacts and additional confirmatory testing.
We have shown that although LFTs will pick up a proportion of true cases of infection, varying proportions will also be missed depending on the presence of symptoms, time from onset of symptoms, likelihood of exposure to people who are infected and study setting. The balance of benefit to harm from testing, and the relative impact from false negative or false positive results, is not only affected by variations in the accuracy of the tests but changes depending on the underlying percentage of people with confirmed COVID-19 (prevalence) amongst those being tested.
Below, we show this changing balance of benefits and harms in the examples below using summary results for people with and without symptoms of COVID-19.
Using LFTs in people with symptoms of COVID-19
Using summary results for symptomatic people tested during the first week after symptoms began, if 1000 people with symptoms had the antigen test, and 50 (5%) of them really had COVID-19:
- 45 people would test positive for COVID-19. Of these, 5 people (11%) would not have COVID-19 (false positive result).
- 955 people would test negative for COVID-19. Of these, 10 people (1.0%) would actually have COVID-19 (false negative result).
The higher the underlying prevalence of infection in a population (risk of having COVID-19), the more a positive LFT test can be relied on to correctly identify infection, however the risk of the LFT missing true cases of infection also increases, such that a negative LFT cannot be relied on to rule out infection.
Using LFTs in people with no symptoms of COVID-19
In people with no symptoms of COVID-19 the number of confirmed cases is expected to be much lower than in people with symptoms. Using summary results for people with no known exposure to COVID-19 in a bigger population of 10,000 people with no symptoms, where 50 (0.5%) of them really had COVID-19:
- 62 people would test positive for COVID-19. Of these, 30 people (48%) would not have COVID-19 (false positive result).
- 9938 people would test negative for COVID-19. Of these, 18 people (0.2%) would actually have COVID-19 (false negative result).
Lower LFT sensitivity in asymptomatic people combined with lower underlying prevalence of infection means that although some true cases are correctly identified, a significant proportion of people with a positive LFT result will have falsely positive results and, along with their close contacts, would have to take unnecessary time off work or school. The impact from false positive results could be lessened by following up with a PCR test.
What do the results of the review mean?
In people with symptoms, some rapid antigen tests are accurate enough to replace PCR, especially when the LFT result is positive, or can be used to identify which people with symptoms need further testing with PCR, thereby reducing the burden on laboratory services. LFTs are less good at ruling out infection in symptomatic people – individuals who receive a negative rapid antigen test result may still be infected.
LFTs are less accurate when used in people with no symptoms of COVID-19. More evidence is needed to understand the accuracy of rapid testing in people without symptoms and the extent to which different testing strategies can lead to reduced transmission, either for tests carried out at home or in non-healthcare settings such as schools.
Please note, we cannot give specific medical advice and do not publish comments that link to individual pages requesting donations or to commercial sites, or appear to endorse commercial products. We welcome diverse views and encourage discussion but we ask that comments are respectful and reserve the right to not publish any we consider offensive. Cochrane UK does not fact check – or endorse – readers’ comments, including any treatments mentioned.
Dinnes J, Sharma P, Berhane S, van Wyk SS, Nyaaba N, Domen J, Taylor M, Cunningham J, Davenport C, Dittrich S, Emperador D, Hooft L, Leeflang MMG, McInnes MDF, Spijker R, Verbakel JY, Takwoingi Y, Taylor-Phillips S, Van den Bruel A, Deeks JJ. Rapid, point-of-care antigen tests for diagnosis of SARS-CoV-2 infection. Cochrane Database of Systematic Reviews 2022, Issue 7. Art. No.: CD013705. DOI: 10.1002/14651858.CD013705.pub3.
Declaration of interests:
Dr. Dinnes reports grants from NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham (Grant Reference Number BRC-1215-20009), during the conduct of the study.