With the coronavirus (COVID-19) pandemic continuing to surge globally, there are new questions about testing, including what kind of tests are available and whether you should get one. Widespread availability of diagnostic testing is critical in helping identify and control the emergence of this rapidly spreading and serious illness. As of August 2020, the Food and Drug Administration (FDA) has officially authorized more than 100 manufacturers to make molecular tests (10 of which you collect at home yourself) and two manufacturers for antigen tests, the newest type of diagnostic test. There have been over 25 manufacturers authorized to distribute serological tests.
There is an enormous amount of information being reported about COVID testing — from at-home testing to portable/point-of-care tests with faster results — that it may be difficult to keep track of when and where these tests will be available. The information below is an effort to keep everyone abreast of the latest testing information.
What is the molecular test, and how does it work?
In a patient with a COVID-19 infection, genetic material from SARS-CoV-2, the virus that causes COVID-19, is generally detectable in upper and lower respiratory specimens. Molecular tests are the gold standard diagnostic test for SARS-CoV-2. Molecular tests are routinely used to detect the presence of viral genetic material in a sample. The specific technique that is used is called reverse transcription polymerase chain reaction, or RT-PCR, where genetic material from a sample is copied and then compared to the genetic sequence of the virus you are trying to detect.
How do provider-administered swab tests for coronavirus work?
Obtaining a respiratory sample for molecular tests typically involves a nasopharyngeal (NP) swab. While there are several methods of collection, in general, it starts by inserting a 6-inch-long swab into the back of the nasal passage through one nostril and rotating the swab for several seconds. The swab is then inserted into a container and sent to a lab for testing. This type of testing is/has been used to test for respiratory pathogens and viruses (think influenza) for decades. The time needed to obtain a result is quite variable. However, the response times for tests used at UofL Health are within 24 hours of the lab getting the specimen, according to Eyas Hattab, M.D. “Our laboratory runs multiple platforms that vary in their testing capacity and turnaround time. This provides us with the agility needed to meet the demands of a complex health system. Our average turnaround time has been just over three hours, which is quite remarkable. As we expand our testing capacity, we are incorporating higher-throughput instruments which have a higher turnaround time.”
Why is there so much variability in reporting with some reports saying test results are not returning for weeks?
The biggest problem facing outside lab testing is not the test itself, but rather the availability of the reagents needed to run the tests compared to the number of samples being sent. Think of this as the dough needed to bake. While your oven maybe able to handle baking 50 cookies at a time, if you only have enough dough for 10 cookies, that will be all you can bake at that time. The supply of testing is far outstripped by demand, thus there are delays in running the tests themselves.
What about rapid molecular tests?
Alternative testing methods have recently been introduced, including rapid diagnostic tests that can be analyzed where the sample is collected at point-of-care (e.g., clinic, ED, doctor’s office), and results are available in minutes. There are currently four authorized rapid point-of-care diagnostic tests, including ID NOW by Abbott, Xpert Xpress by Cepheid, Accula by Mesa Biotech, and Cue COVID-19 Test by Cue Health, Inc. Per Dr. Hattab, “Rapid diagnostic tests for COVID are invariably designed to identify viral antigens, aka antigen tests. These tests generally offer less sensitivity and specificity compared to PCR but offer the advantages of ease of use and quick turnaround time making them ideal for office settings and wide community-based surveillance.”
What about at-home tests for coronavirus?
The FDA has authorized several at-home collection molecular tests, including Pixel by LabCorp and tests by Everlywell and LetsGetChecked, which are available online. The test kits contain supplies to collect samples, including a nasal swab which you send back to the lab for testing. Unlike other swab-based tests, these tests use swabs that only need to go as far as the nostril, instead of deeper into the nasal passage. A recent study led by the UnitedHealth Group suggests that results from self-collected swab tests are similar in accuracy to provider-collected swab tests.
However, other studies have called this into question. Dr. Gary Procop, a pathologist at the Cleveland Clinic, discussed the concerns regarding accuracy of specimen in this article. In particular, he notes, that due to the cost and the concern regarding variability in specimen collection, this may not be the best option available right now. I would agree that testing simply out of curiosity is not advisable, and if you have symptoms, you should see a medical professional.
What about the at home saliva kits? How are they different?
Several companies, including Hims and Vault Health, are now offering at-home collection tests online using a saliva test developed by Rutgers’ RUCDR Infinite Biologics. Test kits include a collection device to collect your saliva (instead of deep nose or throat swabs) and the sample is then mailed to the lab for processing. This is still a rather new technology, and as of this writing, I cannot validate or refute this as a testing modality. My overall concern is the same as the nasal swab at home testing options above. They are probably not useful if you are asymptomatic, may take a while to result, the out-of-pocket cost is not insignificant, and require the consultation with a medical professional if they return positive.
How accurate are molecular coronavirus tests?
A positive result indicates an active COVID-19 infection but does not rule out concurrent bacterial infections or co-infections with other viruses. Both clinical scenarios have been reported throughout this pandemic; thus, I would strongly recommend discussing any positive test result or symptom with a medical professional.
However, there is a small chance that it could be a false positive, meaning that the test is positive, but you do not have a COVID-19 infection. As with every test, there is a limit at which you can still detect a signal and, in general, the RT-PCR molecular test is very sensitive to detecting the virus. This has led to speculation (but not confirmation) that there might be an elevated false-positive rate using this type of test as a screening option. A false negative is also possible but much less likely, and should be considered in combination with your symptoms, travel history, and other possible ways of having been exposed. Additionally, the FDA advises anyone who tests negative with the saliva-based test to confirm the results with a second testing method. As with most COVID-19 tests, the variability of the testing platform and thus the false negative and false positive rate is caused by suboptimal sample collection.
What is the COVID-19 antigen test, and how does it work?
As discussed above, antigen tests are the newest diagnostic test for SARS-CoV-2. Currently, two companies have been issued authorization by the FDA to distribute these tests. Antigen tests tend to be lower cost for manufacturers to make due to their simpler design, allowing testing to scale up more quickly.
What is the science behind antigen testing?
While molecular tests detect viral genetic material, antigen tests detect specific proteins on the surface of the virus. Antigen test samples are collected just like molecular tests, using nasal or throat swabs. The swab is then placed into a tube with special chemicals to expose the proteins, and the sample is dispensed into a cassette that is placed into the testing device to get your results.
How long does it take to get results with antigen tests?
The speed and portability of antigen testing is another benefit. The two authorized antigen tests, which include Sofia 2 SARS Antigen FIA by Quidel Corporation and BD Veritor Plus SARS-CoV-2 Assay by BD, produce results in 15 minutes.
How accurate are antigen coronavirus tests?
Compared to molecular tests, antigen tests are useful due to their speed but are not as sensitive, meaning that there is a greater chance of a false-negative result. However, they are very specific for the virus so positive results are going to be highly accurate.
If your antigen test comes back positive, it is very likely that you have the virus. If your test comes back negative and you are having symptoms, you will probably want to confirm your negative result using a molecular test.
What is the serological (antibody) test, and how does it work?
Unlike diagnostic tests, serological tests can identify people who were infected and have recovered. One of the early problems in the pandemic was that the FDA was not authorizing serological tests. However, an influx of unreliable and/or inaccurate tests flooded the market, prompting a policy change. Developers now have 10 days from the date of notifying the FDA of a new test to submit an authorization request to the FDA and must meet certain performance thresholds for accuracy. The FDA currently maintains a list of serological tests that should no longer be distributed because the manufacturers either did not submit an authorization request within the designated timeframe or there were significant problems with the test that cannot or have not been addressed. As of August 2020, the FDA has granted over 25 authorizations for serological tests, and over 170 additional tests are pending authorization. Additionally, 70 tests are currently on the list of tests that should no longer be distributed.
How is the testing sample collected for the serological test?
Serological tests rely on detecting antibodies in a blood sample, usually obtained through a simple finger prick or venous blood collection. These tests do not require special equipment to process the results, which allows them to be used in laboratories or at point-of-care.
Currently, there are no authorized at-home antibody tests.
What is the science behind it?
When you are exposed to the virus, over several days to several weeks, your body develops antibodies to the virus. In general, the presence of immunoglobulin M (IgM) antibodies indicates recent exposure to COVID-19, while the presence of immunoglobulin G (IgG) antibodies indicates later-stage infection. The rapid response serological tests typically use a technique called enzyme-linked immunological assay (ELISA), which detects the presence of these antibodies to the coronavirus.
How accurate are serological tests?
Since it can take several days to weeks for the body to develop an antibody response to the virus, serological tests may not be useful in identifying a current infection alone. They might make you think you do not have an infection when you do. The FDA has summarized the estimated accuracy of the authorized serological tests here.
A recent Cochrane review of 54 studies suggests that timing of the test is also important for the accuracy of results, with the highest accuracy 3 weeks after onset of symptoms. According to the review, tests conducted one week after symptom onset only detected 30% of people who had the virus. After two weeks, accuracy increased to 70%. After three weeks, more than 90% of positives were detected. Most of the study participants were more likely to have severe disease since they were hospitalized with COVID-19.
The bottom line is that we still do not know the accuracy of antibody tests for people who are asymptomatic or have mild symptoms since their immune response may be different than those with severe disease. In the current clinical realm, antibody testing has limited utility.
How much does it cost to get tested?
Of all questions I am asked, this is the most frequent. The Families First Coronavirus Response Act mandates that COVID-19 testing is free whether you have insurance or not, meaning that you will not have to pay anything out of pocket for medical services related to COVID-19 diagnostic testing. As of this writing no patient that UofL Health has tested has received an out of pocket expense for the actual COVID-19 diagnostic test. If you are tested for COVID-19 as a referral from your provider, or you are being tested to facilitate a procedure at UofL Health, your insurance may cover this cost, but you as a patient should not receive any bill for testing. Additionally, UofL Health has partnered with the Commonwealth of Kentucky to provide free testing for anyone who lives in the Commonwealth. If you want to be tested for COVID-19 you can sign up for the state testing program and you will incur no out of pocket cost.
Who should be tested for COVID-19?
Since the beginning of the pandemic, this has been a moving target for health care providers and public health agencies. As of August 2020, the Centers for Disease Control and Prevention (CDC) has detailed five groups of people who should be tested for SARS-CoV-2:
- People with signs and symptoms of COVID-19
- People who are asymptomatic but have recent known or suspected exposure to the virus
- Certain people who tested positive and are being retested to see if the infection has cleared (more on this below)
- People being tested for public health surveillance for SARS-CoV-2
- People who are asymptomatic without known or suspected exposure in special settings (certain cancer patients, transplant patients and those with significant underlying conditions)
If I am asymptomatic and do not fall under a special setting criterion should I get tested?
In a word: No. In the CDC guidance linked at the end of this document, they recommend narrowing the range of the testing from just the general population to focus on at risk groups noted above, areas of high infection rate and or localized outbreaks.
Once you have tested positive for the virus, do you need to keep testing until you get a negative result?
Again, in a word: No, at least for right now while testing resources are strained. The CDC has recently updated its guidance to advise against using consecutive tests to decide when a person who has tested positive is no longer contagious and can stop isolating. In many cases, people may continue to test positive for SARS-CoV-2 long after their symptoms have resolved and they are no longer contagious, resulting in prolonged isolation that is unnecessary. This is a drawback to using a highly sensitive test like RT-PCR (molecular) testing. Additionally, with the rising demand for testing across the country, repeat tests may backlog the system and delay results for others.
So doctor, give me the bottom line.
If you are having any type of symptom, you need to get tested for COVID. If you have an active COVID-19 infection, the molecular test will tell you with the best reliability if you have an infection. The serological (antibody) test will be able to tell you if you have had the infection (regardless of having symptoms or not) but are not useful in treating or identifying the disease clinically. Very soon, rapid response, point-of-care tests will be deployed to ease testing concerns, at home tests are probably not a good option as of right now.