While COVID-19 testing in the U.S. has been an issue throughout the pandemic, the release of vaccines has further complicated the picture. So, let’s try to sort out some of the confusion.

Types of tests

COVID-19 testing falls into two main categories, virus and antibody testing.

Virus testing is important for determining whether someone is currently infected, and quick turnaround of these tests is critical for contact tracing. Not only have limited availability of tests and long turnaround times been at issue, so, too, has been a politicization of the common public health practice of contact tracing, which can be used to slow the spread of an infectious agent. While the widespread disease at this point makes contact tracing less useful, many people still need testing for jobs, travel or diagnosis.

When evaluating for the presence of virus, tests can evaluate the presence of viral proteins or viral RNA in samples; the latter are often referred to as molecular tests. While both of these approaches are based on the presence of virus, molecular tests are more sensitive, as they employ reverse transcriptase polymerase chain reaction (RT-PCR) technology to amplify RNA in the samples. Samples are typically collected by nasal swab or saliva, but respiratory lavage can also be used for the nucleic acid-based tests. Important context when evaluating or discussing results of virus tests is timing after exposure when the sample was taken and quality of sample collection.

The FDA has approved several tests that are posted on their website along with summary information and links to relevant documents (e.g., patient information, instructions for use, etc.):

Antibody testing is important for determining whether someone was previously infected. Antibody testing is also important for studies related to reinfection, markers for protection, and understanding COVID-19 treatments, such as convalescent plasma.

Antibody tests rely on blood samples and evaluate the presence of antibodies of different types (e.g., IgM or IgG) and specificities (e.g., spike protein or nucleoproteins). Timing of sample collection is important because if an antibody test is administered too soon after infection, antibody levels may not be high enough for detection.

The FDA has approved several serological tests, which are posted on their website with summary information and links to relevant documentation:

Effects of vaccines

People have been wondering whether vaccination confounds the testing results, and as such, whether someone who has been vaccinated can — or should — still get tested. Right now, we don’t know if a person who was vaccinated can still be infected, and we know that while the vaccines have demonstrated high levels of effectiveness, not everyone will be protected following vaccination. For these reasons, testing is still important in certain situations following vaccination. So, what should be considered related to testing after vaccination?

COVID-19 mRNA vaccines deliver the nucleic acid for the SARS-CoV-2 spike protein, and these vaccines are processed locally, meaning near the injection site. As such:

  • Whole virus is never produced.
  • Virus particles or individual proteins do not travel through the body, which means they cannot be found in nasal or salivary secretions.

As a result, vaccination does not interfere with the viral testing used to evaluate someone for current infection.

On the other hand, vaccination does cause the generation of antibodies, and therefore needs to be considered in the context of antibody testing. Because only the spike protein is introduced by the mRNA vaccines, antibodies generated by vaccination will only be specific for the spike protein. As such, tests that evaluate antibodies to nucleoproteins can distinguish between vaccination and infection.

Current recommendations and considerations

The Centers for Disease Control and Prevention (CDC) has not changed routine testing guidelines following possible exposure. Therefore, if someone is exposed, having symptoms, or think they might have been exposed, they should follow guidance related to quarantine or isolation, including viral testing if appropriate, regardless of their vaccination status.

People should not be antibody tested solely for the purpose of evaluating their need for or response to vaccination. Those previously infected with SARS-CoV-2 are recommended for vaccination because we do not yet know enough about longevity of protection following infection, and we do know that a small number of people have been infected more than once. In a small number of cases, second infections have been severe.

If a vaccinated person requires antibody testing, their sample should be analyzed with an antibody test specific for nucleoproteins. The FDA website has a list of these tests on their webpage, “EUA Authorized Serology Test Performance.”

Additional resources

