Key messages
• Rapid antigen tests are not as accurate when used in people with no signs or symptoms of infection compared to when they are used in people who have symptoms. They perform better in this latter group who have been in contact with someone who has confirmed COVID-19; however, the evidence is not definitive.
• Accuracy of rapid antigen tests varies across different rapid antigen tests made by different manufacturers. There is a lack of evidence for many tests available on the market, and none fully meet WHO standards for diagnosing COVID-19 in asymptomatic people.
• More evidence is needed to understand if screening people without symptoms can reduce the spread of COVID-19, especially in non-healthcare settings like schools and homes.
What are rapid point-of-care antigen tests for COVID-19?
These tests are used to confirm or rule out COVID-19 infection, both for people with and without symptoms. They have several advantages:
• portable: can be used anywhere, including at home or in non-healthcare settings;
• easier to use than a laboratory-based test: minimal equipment is needed;
• less expensive: they are cheaper than standard laboratory tests;
• no need for a specialist: anyone can use them, and they do not require a specialist operator or setting; and
• quick results: you get results almost immediately.
For this review, we focused on rapid antigen tests (also called ‘lateral flow tests’.) These tests detect proteins on the virus using samples from the nose or throat. They are similar to pregnancy tests and come in disposable plastic cassettes.
Why is this question important?
People without symptoms of COVID-19 need an easy and reliable way to identify whether they are infected. This helps them avoid spreading the virus to others, especially to those at high risk. COVID-19 is usually confirmed with a laboratory test called RT-PCR, which requires specialist equipment and often takes at least 24 hours to produce a result.
Rapid antigen tests make it possible for more people to get tested quickly, even if they have no symptoms. However, it is important to understand how accurate they are and how to use them correctly to avoid false results.
What did we want to find out?
We wanted to know if commercially available, rapid point-of-care antigen tests are accurate enough to reliably diagnose COVID-19 infection in people without symptoms.
What did we do?
We searched for studies that measured the accuracy of rapid antigen tests in people who had no symptoms of COVID-19. These people also had an RT-PCR test to confirm whether they were infected. The studies took place in hospitals, the community or in their own homes.
What did we find?
We reviewed 146 studies, involving 144,250 unique samples. COVID-19 was confirmed in 7104 of these samples. Studies investigated 41 different antigen tests. About 60% of the studies took place in Europe.
Main results
In people with confirmed COVID-19, antigen tests correctly identified COVID-19 infection in an average of 55% of people without symptoms. The tests were slightly more accurate for people who had been in contact with someone infected with COVID-19 (an average of 59% of people with infection were correctly identified) compared to people with no known exposure (an average of 53% of people with infection were correctly identified).
In people without COVID-19, antigen tests correctly ruled out infection in 99.5% of people.
Test accuracy varied for different brands of test. None of the tests met World Health Organization (WHO) standards for confirming or ruling out COVID-19 when tested in people without symptoms. Some tests met the WHO standard in a single study, but not when evaluated in people without symptoms.
Using summary results for people with no known contact with someone who has COVID-19 in a population of 10,000 people with no symptoms, where 50 (0.5%) of them really had COVID-19:
• 67 people would test positive for COVID-19. Of these, 40 people (60%) would not have COVID-19 (false positive result).
• 9934 people would test negative for COVID-19. Of these, 24 people (0.2%) would actually have COVID-19 (false negative result).
Using summary results for people suspected of having had contact with someone who has COVID-19, if 10,000 people without symptoms had the antigen test, and 50 (0.5%) of them really had COVID-19:
• 89 people would test positive for COVID-19. Of these, 60 people (67%) would not have COVID-19 (false positive result).
• 9911 people would test negative for COVID-19. Of these, 21 people (0.2%) would actually have COVID-19 (false negative result).
What are the limitations of the evidence?
Most studies included representative groups of people and interpreted tests in a way that was free of bias. However, studies often did not follow the manufacturer's instructions for using the test or did not test people in real-world conditions (like at the point of care).
Studies were less good at confirming that people didn't have COVID-19 infection. In over half of the studies, there was no attempt to confirm if the people who tested negative were truly free of COVID-19, for example, by considering the time since they were in contact with someone who had COVID-19 symptoms.
There were few studies directly comparing different test brands, so we cannot easily determine which one is best. It is not possible to comment on the relationship between a positive antigen test result and how infectious a person is. There is also not enough information to know whether doing repeated antigen tests lowers the risk of spreading the virus in a group of people.
How up-to-date is this review?
This review updates our previous review and includes evidence published up to 17 February 2022.
Read the full abstract
Accurate rapid diagnostic tests for SARS-CoV-2 infection could help manage the COVID-19 pandemic by potentially increasing access to testing and speed detection of infection, as well as informing clinical and public health management decisions to reduce transmission. Previous iterations of this review provided clear and conclusive evidence of superior test performance in those experiencing possible signs and symptoms of Covid-19. However, test performance in asymptomatic individuals and sensitivity by setting and indication for testing remains unclear. This is the fourth iteration of this review, first published in 2020.
Objectives
To assess the diagnostic accuracy of rapid, point-of-care antigen tests (Ag-RDTs) for diagnosis of SARS-CoV-2 infection in asymptomatic population groups.
Search strategy
We searched the COVID-19 Open Access Project living evidence database from the University of Bern (which includes daily updates from MEDLINE and Embase and preprints from medRxiv and bioRxiv) on 17 February 2022. We included independent evaluations from national reference laboratories, FIND and the Diagnostics Global Health website. We did not apply language restrictions.
Selection criteria
We included test accuracy studies of any design that evaluated commercially produced, rapid antigen tests in asymptomatic people tested because of known or suspected contact with SARS-CoV-2 infection, known SARS-CoV-2 infection or known absence of infection, or those who were being screened for infection. We included evaluations of single applications of a test (one test result reported per person). Reference standards for presence or absence of infection were any laboratory-based molecular test (primarily reverse transcription polymerase chain reaction (RT-PCR)).
Data collection and analysis
We used standard screening procedures with three reviewers. Two reviewers independently carried out quality assessment (using the QUADAS-2 tool) and extracted study results. Other study characteristics were extracted by one review author and checked by a second. We present sensitivity and specificity with 95% confidence intervals (CIs) for each test, and pooled data using the bivariate model. We investigated heterogeneity by including indicator variables in the random-effects logistic regression models. We tabulated results by test manufacturer and compliance with manufacturer instructions for use and according to symptom status.
Main results
We included 146 study cohorts (described in 130 study reports). The main results relate to 164 evaluations of single test applications including 144,250 unique samples (7104 with confirmed SARS-CoV-2) obtained from asymptomatic or mainly asymptomatic populations. Studies were mainly conducted in Europe (85/146, 58%), and evaluated 41 different commercial antigen assays (test kit). Only six studies compared two or more brands of test. Nearly all studies (96%) used RT-PCR alone to define presence or absence of infection.
Risk of bias was high because of participant selection (13, 9%); interpretation of the index test (3, 2%); weaknesses in the reference standard for absence of infection (3, 2%); and participant flow and timing (46, 32%). Characteristics of participants (11, 8%) and index test delivery (117, 80%) differed from the way in which and in whom the test was intended to be used.
Estimates of sensitivity varied considerably between studies, with consistently high specificities. Average sensitivity was 55.0% (95% CI 50.9%, 59.0%) and average specificity was 99.5% (95% CI 99.5%, 99.6%) across the 147 evaluations of Ag-RDTs reporting both sensitivity and specificity (149,251 samples, 7636 cases). Average sensitivity was higher when epidemiological exposure to SARS-CoV-2 was suspected (58.6%, 95% CI 51.4% to 65.5%; 43 evaluations; 15,516 samples, 1483 cases) compared to where COVID-19 testing was reported to be widely available to anyone on presentation for testing (53.0%, 95% CI 48.4% to 57.5%; 103 evaluations; 129,032 samples, 5660 cases); however CIs overlapped, limiting the inference that can be drawn from these data. Average specificity was similarly high for both groups (99.4% and 99.6%). Sensitivity was generally lower when used in a screening context (summary values from 40.6% to 42.1% for three of four screening settings) compared to testing asymptomatic individuals at Covid-19 test centres (56.7%) or emergency departments (54.7%). We observed a decline in summary sensitivities as measures of sample viral load decreased.
Sensitivity varied between brands. When tests were used according to manufacturer instructions, average sensitivities by brand ranged from 36.3% to 78.8% in asymptomatic participants (14 assays with sufficient data for pooling). None of the assays met the WHO acceptable performance standard for sensitivity (of 80%) based on meta-analysis; however, sensitivities from individual studies (where meta-analysis was not possible) exceeded 80% for three assays. The WHO acceptable performance criterion of 97% specificity was met by all but four assays (based on individual studies or meta-analysis) when tests were used according to manufacturer instructions.
At 0.5% prevalence using summary data for asymptomatic people, where testing was widely available and where epidemiological exposure to COVID-19 was suspected, resulting PPVs would be 40% and 33%, meaning that 3 in 5 or 2 in 3 positive results will be false positives, and between 1 in 2 and 2 in 5 cases will be missed.
Authors' conclusions
Evidence for antigen testing in asymptomatic cohorts has increased considerably since the publication of the previous update of this review. Average sensitivities remain lower for testing of asymptomatic when compared to symptomatic individuals; however, there is an indication that sensitivities may be higher where epidemiological exposure to SARS-CoV-2 is suspected compared to testing any asymptomatic individual regardless of indication. Sensitivities were particularly low when antigen tests were used in screening settings. Assays from different manufacturers also vary in sensitivity, indicating the need for appropriate clinical validation of a particular antigen test in a given intended use setting prior to more widespread deployment.
Further research is needed to evaluate the effectiveness of screening programmes at reducing transmission of infection, whether mass screening or targeted approaches, including schools, healthcare setting and traveller screening.
Funding
This paper presents independent research supported by the NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, and the University of Birmingham. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.
Registration
Protocol (2020) doi: 10.1002/14651858.CD013596
