How does a Covid-19 test work?

24th Sep 2020

We’ve been asked by readers whether a Covid-19 test can return a positive result if the person tested only has the common cold rather than Covid-19. 

This is based on the fact that the common cold can be caused by a number of human coronaviruses, which are related to (but not the same as) the new coronavirus which causes Covid-19.

But it’s a misunderstanding of how the main type of test for Covid-19 works.

Understanding the types of test

There are two main types of diagnostic test which can detect the presence of viruses like SARS-CoV-2 (the virus which causes Covid-19). Diagnostic tests tell you whether a person has the virus now, and they’re what we’re normally talking about with programmes like the UK’s contact tracing systems.

Additionally there are antibody tests, also called serology tests, which can detect if someone has had the virus in the past, but not whether they still do. 

The two diagnostic tests are PCR tests and antigen tests. 

PCR (polymerase chain reaction) tests detect the virus’s RNA (genetic material) in a sample. First, various substances are added to the sample (usually a nose or throat swab) taken from the person tested. These substances, enzymes known as “reverse transcriptase” and “DNA polymerase”, work to make many copies of any viral RNA present. 

This is so enough copies are present to be picked up when that sample is then tested. This testing involves specially designed “primers” and “probes” which attach themselves to specific sequences of the virus’s genetic code, and send out a signal that indicates the genetic material has been found. These primers are designed to target unique segments of the virus’s genome. 

Antigen tests, by contrast, do not detect the viral genetic material, but rather usually proteins in the virus. The presence of antigens normally triggers an immune response by the body.  Antigen tests are “not widely used for coronavirus testing currently”.

These terms are sometimes (confusingly) used interchangeably. Professor of Immunology and Infectious Disease at the University of Edinburgh, Eleanor Riley has said: “Tests for the virus (current infection) are often called “antigen” tests – where antigen refers to some component of the virus, typically the external (coat) protein of the virus. However, the test being used for COVID-19 is actually looking for viral RNA (which is technically not a viral antigen).

“So when people talk of “antigen” tests and others talk of tests for viral RNA or “PCR tests” they are actually talking about the same thing.”

We’re going to focus on the accuracy of PCR tests, as the Department of Health and Social Care confirmed to us that all diagnostic tests for Covid-19 in the UK are PCR tests. 

How accurate are PCR tests?

PCR tests are generally seen as the gold standard for Covid-19 testing. The US Food & Drug Administration (FDA) says: “This test is typically highly accurate and usually does not need to be repeated.” Antigen tests are more likely to miss a Covid-19 infection than PCR tests according to the FDA

That’s not to say that PCR tests are perfect. PCR tests can sometimes indicate that someone does not have the virus when they do (false negative). They can also indicate that someone has the virus when they don’t (false positive).

It’s hard to say how many false negatives and positives PCR tests produce. A paper produced for the Scientific Advisory Group for Emergencies (SAGE) in June said that both the false negative and false positive rate were unknown, and noted that the accuracy in an idealized lab setting might not apply in real life conditions as “there may be inefficient sampling, lab contamination, sample degradation or other sources of error.” 

But in general, these tests have “very high specificity”, which means they don’t return many false positives. And what a PCR test won’t do is misinterpret the presence of common cold coronaviruses as the presence of the virus which causes Covid-19. 

The possibility that a test might pick up related viruses that have genetic similarities to the virus you’re looking for (technically known as “cross-reactivity”) is something that is looked at when designing PCR tests. (For example one of the earliest PCR testing protocols, which was published on 13 January, specifically checked that the test did not pick up the four human coronaviruses that cause the common cold.) Results for a range of available PCR tests show that they do not cross-react with any viruses analysed, including other coronaviruses.

Speaking to TheJournal.ie, lecturer in immunology and host-microbe interactions at the Department of Biological Sciences at the University of Limerick, Dr Elizabeth J. Ryan, said that viral tests for current cases of Covid-19 are “very specific” for material that is “only expressed by the Covid-19 virus”.

“Having a cold or flu won’t change that,” Dr Ryan said.

Where some of the confusion might have come about is because of the accuracy of antibody tests. The US Centers for Disease Control and Prevention says: “There is a chance that a positive result means you have antibodies from an infection with a different virus from the same family of viruses.”