You’ve probably heard a lot about COVID-19 this year. And more recently, you might have heard
about viral testing. What are the different types of tests available? What happens to your
samples after a healthcare professional retrieves them from your body? And how can scientists use
these samples to tell whether or not you have been infected by SARS-CoV-2? To answer these questions,
let’s take a look at two categories of viral tests: direct and indirect.
Direct viral tests detect physical parts of the virus itself, such as viral RNA or viral
antigens. A positive result from a direct test usually indicates an active COVID-19 infection.
The most widely used direct test to diagnose COVID-19 is nucleic acid
amplification using Reverse Transcriptase Polymerase Chain Reaction, or RT-PCR.
In RT-PCR, SARS-CoV-2 RNA is extracted from the samples and amplified to detectable levels.
To do this, a sample is taken from the oropharynx or nasopharynx. Then, in the lab,
reverse transcriptase enzymes take the virus’s single-stranded RNA and use it as a template
to create double-stranded DNA. Next, this DNA is copied over and over using PCR,
until millions or billions of replicates have been produced and can be detected. This
process is complex and requires specialized testing equipment, but automation allows for
RT-PCR testing to show results within hours. However, factors such as a sampling backlog,
limited availability of testing kits or lab reagents, or long distances between
the testing site and the laboratory could mean you don’t actually get results for several days.
Antigen tests are another type of direct test currently used to detect active COVID-19
infections. Antigens are molecules on the surface of the virus that trigger the immune system to
produce antibodies, which are unique proteins that attack only the antigens of a specific
virus. In an antigen test for COVID-19, a tissue sample is taken, typically from the nasopharynx,
and tagged antibodies to the SARS-CoV-2 virus are mixed with the sample. If the tagged antibodies
attach to the antigens in the sample, this indicates that the virus is present in the sample.
Rapid COVID-19 antigen tests are relatively inexpensive, can be performed on site rather
than shipping samples to a lab, and can return results in less than an hour.
However, they are not as accurate as nucleic acid amplification tests.
On the other hand, indirect viral tests detect the body’s immune response to a viral infection.
Serologic tests for COVID-19, also called antibody tests or immunoassays, are a type of
indirect viral test that searches a blood sample for the antibodies to SARS-CoV-2.
If these antibodies are detected, this indicates a viral infection occurred at some point in the
past, and may or may not still be active. This is because antibodies are typically produced 1-2
weeks after the onset of infection, and remain in your body after the active infection has ended.
There are a number of antibody detection tests currently being used for COVID-19,
such as Enzyme-Linked Immunosorbent Assays, and chemiluminescent immunoassays.
In these tests, certain colored substrates, or luminescent molecules, indicate the presence of
the antibody in question. Scientists are still determining what level of protection from future
infection SARS-CoV-2 antibodies may provide. If someone tests positive for COVID-19 viral
antibodies, they may be able to donate their blood to those currently battling the disease,
or to laboratories developing treatments. Does a positive direct test result definitely
mean you’ve been infected with the virus and vice versa? Not always. Important
concepts to understand related to viral tests are sensitivity and specificity.
Sensitivity is the ability of a test to correctly identify people who are infected, and specificity
is the ability of a test to correctly identify people who aren’t infected. In other words,
tests that are highly sensitive have a high true positive rate and a low false negative rate,
while tests that are highly specific have a low false positive rate and a high true negative rate.
Nucleic acid amplification tests, for example, are highly specific, because they detect the precise
viral genetic sequence. But the sensitivity of nucleic acid amplification tests for COVID-19
can vary depending on the amplification protocol used, as well as when and
from where the sample is collected. Thanks to viral tests, scientists and healthcare
professionals are able to diagnose patients so they can receive proper treatment, and can
monitor the evolution of public health crises such as the COVID-19 pandemic. With a combination of
increasingly accurate and accessible viral tests, continued adherence of public health measures,
emergence of medications to treat infections, and development of vaccinations to prevent infections,
the current pandemic will eventually come to an end.