First, though, we need to discuss the FDA approval late Friday, May 8, 2020, of a new type of COVID-19 test called an “antigen” test. This type of test quickly detects fragments of proteins found on or within the COVID-19 virus by testing samples collected from the nasal cavity using swabs.

The Emergency Use Authorization (EUA) for this “antigen” test – which can be seen here – was issued to the Quidel Corporation of Athens, Ohio. The name of Qiodel’s test is the “Sofia 2 SARS Antigen FIA” test. It is authorized for use in high and moderate complexity laboratories certified by the Clinical Laboratory Improvement Amendments (CLIA), as well as for point-of-care testing by facilities operating under a CLIA Certificate of Waiver. If you want the scientific details of the test as set forth in the EUA, they are set forth in a footnote.[1]

Now that this new “antigen” test has been approved, let's discuss the three types of COVID-19 tests that are available.

All tests currently authorized by FDA, regardless of type, require a prescription – none is available over the counter. And only a very few allow for home test collection and even those that do allow for home test collection still require that the specimen be sent to a laboratory for analysis.

PCR Tests

The first tests that were available following the realization that we were in a pandemic were the “PCR” tests. “PCR” stands for “polymerase chain reaction”, which is a testing technique that detects the genetic material (in this case RNA) from the virus. These PCR tests are also called “molecular-based Laboratory Developed Tests” (LDTs). They diagnose an active COVID-19 infection and tend to be among the most accurate. But running the tests and analyzing the results can take time – sometimes several days or weeks because the specimen sample has to go to a specific laboratory and the laboratory test can take time to perform the test (particularly given the backlog).

In the “early days” – remarkably only two months ago – PCR tests required that a sample be taken by means of a swab that was inserted up the nose – or in the FDA’s terms a “nasopharyngeal swab” – which is a rather unpleasant experience because the swab has to go “way up there” into the nose. Since the first approval of a “nasopharyngeal swab” test, the FDA has approved for certain tests other, “more convenient” specimen collection areas, including the mid-turbinate (mid nasal), oropharyngeal (essentially the back of the throat), sputum, tracheal aspirates, and bronchoalveolar (from the lungs) areas. And in one case, the FDA has even approved a test of the saliva. The FDA has approved EUAs for over 50 commercial manufacturers and over 20 laboratories for PCR tests.[2]

Serology Tests

"Serology” – also called "antibody" – tests refer to tests that detect antibodies to the coronavirus. Because the antibodies are part of the body's immune response to exposure and not to the virus itself, such testing cannot be used for a diagnosis of a COVID infection. Antibodies are generally detectable in the blood several days after the initial infection, although the duration of time the antibodies are present post-infection is not well known. Individuals may have detectable virus present (i.e., they would test positive on a PCR test) for several weeks following the development of detectable antibodies. If the antibodies are present, it often indicates a past infection but does not exclude recently infected patients who are still contagious.

These tests may be important for guiding the next steps in the fight against the pandemic, such as by providing information on disease prevalence and the frequency of asymptomatic infection, and also by identifying potential donors of “convalescent plasma,” an approach in which blood plasma containing antibodies from a recovered individual serves as a therapy for an infected patient with severe or immediately life-threatening disease. Unfortunately, science has not yet determined how long the antibodies will remain in the body after the infection has been cleared, nor does science yet know whether these antibodies confer immunity (and, if so, what type of immunity) to future infections.

There are many highly questionable serology tests on the market. In the early stages of the pandemic, the FDA allowed commercial manufacturers to market serology tests by only requiring them to “validate” their tests, and then to notify the FDA that the tests have been validated and that they would be labeled to comply with certain labeling restrictions. Widespread problems with the tests – and, in some cases, outright fraud – ensued. On May 4, the FDA decided that enough was enough and it is now requiring that both existing and new commercial manufacturers submit a full EUA. The Agency also established new and strict performance “recommendations” for specificity and sensitivity for all serology test developers. Please see our previous Alert on this change here. So far, FDA has approved only 12 EUAs for Serology/Antibody Tests.[3]

Antigen Tests

As we noted at the outset of this Alert, the FDA has just granted EUA approval for an antigen test. This type of test quickly detects fragments of proteins found on or within the COVID-19 virus.

One of the main advantages of an antigen test is the speed of the test, which can provide results in minutes. However, antigen tests may not detect all active infections as they do not work the same way as a PCR test. Antigen tests are very specific for the virus but are not as sensitive as molecular PCR tests. This means that positive results from antigen tests are highly accurate, but there is a higher chance of false negatives, so negative results do not rule out an infection. Thus negative results from an antigen test may need to be confirmed with a PCR test prior to making treatment decisions or to prevent the possible spread of the virus due to a false negative.

Antigen tests are important in the overall response against COVID-19 as they can generally be produced at a far lower cost than PCR tests. Once multiple manufacturers enter the market, such tests can be scaled up to test millions of Americans per day due to their simpler design, thus helping health care professionals and epidemiologists to better identify infection rates closer to real-time.

Summary

PCR Tests: Will detect whether you have the virus but can be expensive and time-consuming.

Serology/Antibody Tests: Cannot tell if you presently have the virus but will probably tell if you’ve had the virus in the past.

Antigen Tests: Not as sensitive as PCR tests but are very quick and (potentially) very cheap. Positive results are highly accurate. Negative results do not rule out an infection.

[1] According to the EUA, the test product is “a lateral flow immunofluorescent sandwich assay that is used with the Sofia 2 Instrument intended for the qualitative detection of the nucleocapsid protein antigen from SARS-CoV-2 in nasopharyngeal (NP) and nasal (NS) swab specimens directly or after the swabs have been added to viral transport media from individuals who are suspected of COVID-19 by their healthcare provider. The SARS-CoV-2 nucleocapsid protein antigen is generally detectable in respiratory specimens during the acute phase of infection. Positive results are indicative of the presence of the SARS-CoV-2 nucleocapsid protein antigen, but clinical correlation with patient history and other diagnostic information is necessary to determine infection status. Positive results do not rule out a bacterial infection or co-infection with other viruses. Negative results should be treated as presumptive and confirmed with a molecular assay, if necessary, for patient management.”

[2] All of the tests that have been “approved” by the FDA have been approved through the abbreviated Emergency Use Authorization process, which will only remain in effect while the declaration of the pandemic emergency is in effect. No test has received full FDA approval.

[3] This new EUA requirement for serology tests does not apply to tests from laboratories that are certified under the Clinical Laboratory Improvements Amendments (CLIA) to perform high-complexity testing. FDA says that, for those tests, it does not intend to object to the development and use of serology tests where the test has been validated, notification is provided to the FDA, and certain information is included in the test reports.