Update (24 Mar 2021) Rapid, point‐of‐care antigen and molecular‐based tests for diagnosis of SARS‐CoV‐2 infection

How accurate are rapid tests for diagnosing COVID‐19?

What are rapid point‐of‐care tests for COVID‐19?

Rapid point‐of‐care tests aim to confirm or rule out COVID‐19 infection in people with or without COVID‐19 symptoms. They:

‐ are portable, so they can be used wherever the patient is (at the point of care);

‐ are easy to perform, with a minimum amount of extra equipment or complicated preparation steps;

‐ are less expensive than standard laboratory tests;

‐ do not require a specialist operator or setting; and

‐ provide results ‘while you wait’.

We were interested in two types of commercially available, rapid point‐of‐care tests: antigen and molecular tests. Antigen tests identify proteins on the virus; they come in disposable plastic cassettes, similar to pregnancy tests. Rapid molecular tests detect the virus’s genetic material in a similar way to laboratory methods, but using smaller devices that are easy to transport or to set up outside of a specialist laboratory. Both test nose or throat samples.

Why is this question important?

People with suspected COVID‐19 need to know quickly whether they are infected, so that they can self‐isolate, receive treatment, and inform close contacts. Currently, COVID‐19 infection is confirmed by a laboratory test called RT‐PCR, which uses specialist equipment and often takes at least 24 hours to produce a result.

Rapid point‐of‐care tests could open access to testing for many more people, with and without symptoms, potentially in locations other than healthcare settings. If they are accurate, faster diagnosis could allow people to take appropriate action more quickly, with the potential to reduce the spread of COVID‐19.

What did we want to find out?

We wanted to know whether commercially available, rapid point‐of‐care antigen and molecular tests are accurate enough to diagnose COVID‐19 infection reliably, and to find out if accuracy differs in people with and without symptoms.

What did we do?

We looked for studies that measured the accuracy of any commercially produced, rapid antigen or molecular point‐of‐care test, in people tested for COVID‐19 using RT‐PCR. People could be tested in hospital or the community. Studies could test people with or without symptoms.

Tests had to use minimal equipment, be performed safely without risking infection from the sample, and have results available within two hours of the sample being collected.

What we found

We included 64 studies in the review. They investigated a total of 24,087 nose or throat samples; COVID‐19 was confirmed in 7415 of these samples. Studies investigated 16 different antigen tests and five different molecular tests. They took place mainly in Europe and North America.

Main results

Antigen tests

In people with confirmed COVID‐19, antigen tests correctly identified COVID‐19 infection in an average of 72% of people with symptoms, compared to 58% of people without symptoms. Tests were most accurate when used in the first week after symptoms first developed (an average of 78% of confirmed cases had positive antigen tests). 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, antigen tests correctly ruled out infection in 99.5% of people with symptoms and 98.9% of people without symptoms.

Different brands of tests varied in accuracy. Pooled results for one test (SD Biosensor STANDARD Q) 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 standards (Abbott Panbio and BIONOTE NowCheck) in at least one study.

Using summary results for SD Biosensor STANDARD Q, if 1000 people with symptoms had the antigen test, and 50 (5%) of them really had COVID‐19:

‐ 53 people would test positive for COVID‐19. Of these, 9 people (17%) would not have COVID‐19 (false positive result).

‐ 947 people would test negative for COVID‐19. Of these, 6 people (0.6%) would actually have COVID‐19 (false negative result).

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 SD Biosensor STANDARD Q in a bigger population of 10,000 people with no symptoms, where 50 (0.5%) of them really had COVID‐19:

‐ 125 people would test positive for COVID‐19. Of these, 90 people (72%) would not have COVID‐19 (false positive result).

‐ 9,875 people would test negative for COVID‐19. Of these, 15 people (0.2%) would actually have COVID‐19 (false negative result).

Molecular tests

Although overall results for diagnosing and ruling out COVID‐19 were good (95.1% of infections correctly diagnosed and 99% correctly ruled out), 69% of the studies used the tests in laboratories instead of at the point‐of‐care and few studies followed test manufacturer instructions. Most of the data relate to the ID NOW and Xpert Xpress tests. We noted a large difference in COVID‐19 detection between the two tests, but we cannot be certain about whether results will remain the same in a real world setting. We could not investigate differences in people with or without symptoms, nor time from when symptoms first showed because the studies did not provide enough information about their participants.

How reliable were the results of the studies?

In general, studies that assessed antigen tests used more rigorous methods than those that assessed molecular tests, particularly when selecting participants and performing the tests. Sometimes studies did not perform the test on the people for whom it was intended and did not follow the manufacturers’ instructions for using the test. Sometimes the tests were not carried out at the point‐of‐care. Nearly all the studies (97%) relied on a single negative RT‐PCR result as evidence of no COVID‐19 infection. Results from different test brands varied, and few studies directly compared one test brand with another. Finally, not all studies gave enough information about their participants for us to judge how long they had had symptoms, or even whether or not they had symptoms.

What does this mean?

Some antigen tests are accurate enough to replace RT‐PCR when used in people with symptoms. This would be most useful when quick decisions are needed about patient care, or if RT‐PCR is not available. Antigen tests may be most useful to identify outbreaks, or to select people with symptoms for further testing with PCR, allowing self‐isolation or contact tracing and reducing the burden on laboratory services. People who receive a negative antigen test result may still be infected.

Several point‐of‐care molecular tests show very high accuracy and potential for use, but more evidence of their performance when evaluated in real life settings is required.

We need more evidence on rapid testing in people without symptoms, on the accuracy of repeated testing, testing in non‐healthcare settings such as schools (including self‐testing), and direct comparisons of test brands, with testers following manufacturers’ instructions.

How up‐to‐date is this review?

This review updates our previous review and includes evidence published up to 30 September 2020.