COVID-19 Tests: what are the options?

In general, there are 4 types of tests used to detect virus infections, 2 of which are currently relevant for COVID-19.

1. Cultures: this is the gold standard for determining what has caused a virus infection, but it is difficult to do, takes weeks to perform, is very expensive, and can only be performed in highly specialized labs. It is impractical for use in a pandemic, except as a research tool.

2. Antigen tests: these tests look for special proteins found on the surface of the virus. It is generally not a very accurate test and therefore it is not generally used for diagnosis. It is useful as a screening tool for some infections (such as strep throat), but it is horribly unreliable for most viruses. No antigen test for COVID-19 has been approved at this stage and there are none on the horizon. If one is eventually approved, it is not clear yet whether it will be of any value in screening for COVID-19.

3. DNA or RNA moleculartests: this type of test looks for the genetic material of the virus (in the case of COVID-19, that’s RNA). It is commonly referred to as an RT-PCR test. Samples are taken from the back of the nose or throat and the test looks for COVID-19 virus RNA in the sample. The problem is, there is not much RNA material and the test only “sees” tiny bits. That makes the test prone to a lot of false negatives, meaning that the test fails to detect the virus in someone who has the virus. The sensitivity depends on the stage of infection. In the early stages of infection with COVID-19, the test works about 70% of the time, but after 5-7 days that number drops to 40%.

In addition to poor sensitivity, there are other problems with the RT-PCR test. It is quite expensive, requiring special equipment, chemical reagents, and highly trained individuals to perform it. It is labor-intensive and collecting specimens takes skill. Poor collection technique is a common cause of false negatives. The specimens are usually transported to a lab, which means they can get lost, mixed up, and mislabeled. Shortages of transport medium have been a problem and improper handling may result in the test losing effectiveness. Turn around time for the test is often quite slow, which is why we have been hearing about so many tests “pending”. Finally, the biggest problem with this test has been simply a lack of capacity. Why have we tested so few people? Because we don’t have enough capacity to test more.

So if there are so many problems with RT-PCR tests, why are they used and why do some people say it is the standard? There are 2 reasons. Firstly, it was the only thing we had when this pandemic started, so we used what we had. Secondly, when it is positive, it is usually correct. It tells us the patient is actively infected. That, of course, was of paramount importance early on, when identifying actively infected individuals was the most important thing.

4. #Antibodytests: Antibodies are what the body produces to fight against infection. Antibodies attach themselves to proteins on the surface of the virus (the antigens) and in doing so they disable the virus. Antibodies are specific, meaning that they attach themselves to a specific antigen. Finding antibodies to the COVID-19 virus in a patient’s blood means they have been exposed to the virus at some point. Antibody tests are therefore useful in determining who has had an infection.

There are 2 types of antibody tests: ELISA tests and #lateralflowtests, commonly called #rapidtests. Both tests look for antibodies. The ELISA test is done in a lab using an “assay” (a mixture of chemicals) and the lateral flow rapid test is a point-of-care test that looks a lot like a home pregnancy test. Both are highly accurate in the detection of antibodies several days after the onset of an infection. Elisa tests require a laboratory setting and are performed by trained laboratory technicians. Lateral flow rapid tests are self-contained units that can be used immediately “in the field” with a finger pick sample. They are low cost, easy to use, require no special training, are completely portable, and are quick (results in 10-15 minutes).

These antibody tests detect IgM and IgG antibodies. In general, IgM antibodies are detectable in the blood several days after a virus infection begins, while IgG antibodies become detectable slightly later and remain around after recovery. Because COVID-19 is a new virus, the patterns for antibody levels over the course of COVID-19 infection are not well understood. We simply do not know how soon COVID-19 antibodies appear and how long they remain. We do know that early on, in the first few days of infection, antibodies may not be present, so a negative test is likely. After ~ 3-5 days we expect the results to turn positive. Positive results for both IgG and IgM could, therefore, indicate an acute (active) infection or infection in the past (post-recovery).

The presence of IgG antibodies is generally associated with some resistance or immunity to future infection, however, we do not know how long immunity lasts with COVID-19. Adding further to the confusion, many viruses mutate, which means the surface proteins change and antibodies no longer work. No one knows whether or not COVID-19 will mutate.

So, where does this leave us? There are lots of unknowns but here’s what we do know:

RT-PCR Tests:

  • Detect virus infection in the first few days of infection

  • When positive they are helpful in understanding who has COVID-19 now

  • They are expensive, require special equipment, are slow, and quickly lose accuracy after 5 days of infection.

Lateral Flow Rapid Antibody Tests

  • Detect antibodies to the virus

  • Are helpful in understanding who has already had COVID-19

  • Are inexpensive and require no special skill or equipment and therefore can be used for mass screening and long term follow-up

Both tests have value. The values are different.

We need both types of tests and we need both now.