Screening approaches for COVID-19 are evolving and include diagnostic tests for active infection with SARS-CoV-2 (the virus that causes COVID-19), serological assays for screening past infection and other less precise screening methods to identify potential cases of COVID-19 and minimize risk.
Diagnostic Tests to Detect Current or Past Infection
While not yet widely commercially available, there are hundreds of diagnostic tests being developed around the world. As of mid-April 2020, over three dozen commercially available tests had been authorized by the U.S. Food and Drug Administration (FDA) under an Emergency Use Authorization (EUA).1
Additionally, FDA has stated that they will not object to the use of tests that have not received EUA, as long as they have been validated and authorized under processes established by the state in which they are conducted. Commercial developers may also supply their tests after they have been validated according to FDA’s recommendations and while they are preparing their request for EUA. However, commercial developers that intend to supply their tests before receiving EUA should provide instructions for use and post data about the test’s performance characteristics on their website.
All of these tests, FDA authorized or not, can be grouped into two broad categories based on what the test detects and what information about an individual’s infection status the results provide.
Nucleic Acid Diagnostic Tests: These account for the majority of FDA-authorized tests and work by detecting viral genetic material from swabs taken from the back of the nasal cavity or from saliva. Administration of these tests involves the insertion of a long swab into the back of the nose or throat. For many of these tests, samples must be analyzed at CLIA-certified laboratories, where technicians use RT-PCR (reverse transcription polymerase chain reaction) to amplify copies of viral genetic material. Typical processing time can range from 24 hours to a couple of days, but may be longer depending on location and lab availability. A positive test is a reliable indicator of the presence of the virus in the person tested and also suggests that individual is infectious. Likewise, a negative test in someone that has previously tested positive for COVID-19 is a reliable indicator that the individual is no longer infectious.
Recently, the FDA has also authorized point-of-care tests. These rely on similar technology, but utilize specialized, automated equipment to process and analyze specimens in a single machine, delivering onsite results in under 45 minutes.2 These tests may be performed in a patient care setting by appropriately trained staff, such as hospitals, physician’s offices, urgent care and temporary patient care settings that are operating under a CLIA Certificate of Waiver or Certificate of compliance3. Recent experiences, however, have indicated that certain methods of collection and processing may impact the reliability of these tests, leading to false negatives (i.e., negative results when the person is actually infected), and directions on their administration are being updated.
In addition to point-of-care tests, the first coronavirus testing kit that allows for at-home sampling received EUA approval by FDA on April 21. Other suppliers had begun marketing at-home testing kits in March, but the FDA has since confirmed these other tests were unauthorized. For these at-home sampling kits, individuals use a sterile cotton swab (similar to a Q-tip) to collect a sample from a shallow part of their own nasal cavity. The swab is then sent to a commercial lab for testing. Currently, these kits are available only to health care workers and first responders following completion of a health screening questionnaire. However, these kits and other at-home sampling tests may be made more broadly available in the coming weeks, though a health care provider will still have to order the test based on the results of a questionnaire.
Immunoassays: Immunoassays detect antibodies that individuals produce when infected with SARS-CoV-2. Thus they detect the body’s immune response to the virus, rather than the virus itself. The most common of these tests use structural components of the virus to capture and detect two types of antibodies: IgM (immunoglobulin M) and IgG (immunoglobulin G). IgM antibodies are produced early on and persist throughout infection. IgG antibodies, on the other hand, are produced only after an individual has mounted an immune response, which can occur between 1-4 weeks after initial infection.
These tests require blood samples from the patient, and the amount of blood needed varies with the type of test. Some tests require a blood draw from a vein and others only need a finger prick. Currently, these tests must be processed in a CLIA-certified facility and ordered by a physician,4 but can generate results in 20-60 minutes.
At present, the FDA does not recommend the use of these tests as the sole basis for diagnosing COVID-195 and a negative test should not be interpreted to mean that an individual is not currently infected with the virus. Because these tests rely on antibodies that need time to accumulate, they are not effective in identifying the early stages of infection, and when COVID-19 is suspected, a nucleic acid test should be used to rule out active infection. However, when used in combination with clinical data and other test results, these tests may help detect recent infections.
The other main application of serological assays is research on disease surveillance (i.e., to better understand how widespread the infection is), but the accuracy and reliability of these tests are still being evaluated. These tests may eventually be useful for assessing if an individual has developed protective immunity, but until these tests have been validated for this purpose, current FDA-authorized tests should not be used to determine whether someone is immune to COVID-19.
FDA has also advised health care providers using these test to understand their limitations and to be aware that FDA is permitting distribution of these tests prior to FDA review and authorization.
Importantly, the sensitivity (the likelihood of correctly diagnosing an infected individual) and specificity (the likelihood of correctly diagnosing an uninfected individual) of both kinds of tests can be affected by a number of factors, such as the status of the person’s infection at the point of sample collection and testing protocol compliance. Accordingly, a negative result from any of the tests described above may require interpretation from a licensed medical professional in light of other diagnostic criteria.
Other Screening Methods
Because many employers may not be able to implement diagnostic testing in the near-term or may not be able to implement on-site testing, they may turn to other methods to screen their employees for possible COVID-19 infection.
Temperature Screening: Perhaps one of the easiest diagnostic tests to administer, temperature screening allows employers to identify possible symptomatic cases, as fever is one of the symptoms of an active COVID-19 infection. Since other types of diseases, such as influenzas and colds, also commonly present with a fever, a temperature screening protocol may also reduce the spread of other diseases in the work place.
Questionnaires: Another simple screening method is to have employees complete a questionnaire about recent symptoms (i.e., within the prior two weeks) that could indicate infection, exposure to known cases, and activities that increase risk, such as travel to areas with higher numbers of cases.6 Known signs and symptoms for COVID-19 range from mild to severe and can include:7
- Sore throat
- Shortness of breath or difficulty breathing
- Muscle pain
- New loss of taste or smell
- Repeated shaking with chills
Because many COVID-19 cases are asymptomatic and employees may have been exposed to the virus without knowing it, these methods are not as effective at identifying infections as diagnostic testing. However, they are practical risk stratification methods, and may help to reduce the spread of the virus.
Regardless of the screening methods used, employers should develop policies and procedures for how to respond if possible or confirmed exposure or infection is identified.