What Should You Know About COVID-19 Testing? A Detailed Overview

With the rising need for a reliable COVID-19 diagnostic test suitable for widespread use, the media has been flooded with an overwhelming amount of information about different types of tests, their efficiency, and potential.

Countrless speculations, partial truths, and talks about using antibody tests for “immunity passports” or “risk-free certificates” are also doing the rounds, even though the WHO warns that there’s still no scientific merit for that. The emergence of commercially available COVID-19 tests and at-home kits is also raising questions about which tests are reliable, when and if you should get them, and how they work. 

At the moment, two main types of diagnostic tests are in use; PCR tests that look for the presence of the virus, and serological tests that test for antibodies, the body’s response to the virus. Recently, scientists found a third approach that uses the gene-editing CRISPR system.

What should everyone know about COVID-19 testing?

SARS-CoV-2 and our immune response: What do the tests look for? 

The SARS-CoV-2 virus is a nucleic acid carrying genetic information — RNA wrapped in proteins. Once it enters the cells, it can hijack their machinery for turning genetic information to protein, reassemble itself again, and go to infect other cells. In the first week, while the virus is actively spreading and the immune system is still in the process of responding, we can search for that RNA.

Chinese scientists sequenced (decoded) the genetic material of SARS-CoV-2 back in February which is why we can now attempt to isolate RNA from potentially infected people and check if that code is the same as the one they’ve found.

We do that using the so-called polymerase chain reaction or PCR test.

When the starting material is RNA and not DNA, we use a variation of this test called RT-PCR. It’s meant to tell us if there is a virus in our organism, but sometimes it gives false negative results because we didn’t pick up the virus when taking a swab. Levels of RNA start to decline after the first week, but that’s when our immune response reaches its peak.

Antibodies can neutralize the pathogen and block its from doing anything, or they can just bind to it and flag them to be eaten by the T cells. As you might assume, that process takes some time.

This is why we can’t test for antibodies in the blood in the first days of infection. We have five classes of antibodies, and the important ones for COVID-19 testing are called IgM and IgG. Roughly two weeks after the infection, the level of IgG reaches its peak and continues to linger in the blood for two to three months after the battle is over, while IgM appears earlier.

What can the COVID-19 test tell us?

PCR is used to diagnose COVID-19 because it confirms that the SARS-CoV-2 virus is present in your body. For a virus to spread through our body, it needs to multiply its genetic material, which is why there’s a high level of RNA that rises during the first week.

This test is essential for keeping track of how the disease spreads by finding out how many people are infected on a given day. However, it can’t tell you if you’ve already had the disease, or if you’re immune, and it can’t with certainty tell you that you’re not infectious. 

Serological or antibody tests don't look for the virus itself, but for antibodies, evidence of your body’s response to the virus. This is why they can tell if you’ve had the infection in the past, which will be useful in revealing the true extent of the pandemic. 

Normally, the level of IgG antibody lingers in the blood after the infection, just in case a threat comes up again. However, in the case of SARS-CoV-2, we still don’t know if people develop immunity to reinfection.

Remember how the cells of innate immunity present parts of viral proteins they took, so B cells tailor antibodies to those specific proteins? Take into account that some viruses — like the coronavirus or influenza — mutate rapidly, meaning that their proteins change a little. When that happens, that perfect lock-key fit is "broken". This is not specific to COVID-19. It's the reason why you have to get a new flu vaccine every year, and we’ve seen re-infections happen with other strains of coronavirus. 

Then again, these molecules are not actual keys and locks; they have some flexibility and there’s a chance they will still bind to slightly changed proteins. We just can't be sure, and the risk is too high to speculate. 

The accuracy of COVID0-19 tests: Why are we getting false-negative results? How reliable are the tests?

As research advances, evidence that many people who tested negative with a PCR test were, in fact, positive is emerging. Many physicians are publicly addressing their concern for patients with a clinical picture of COVID-19 who have tested negative for the virus. Some prominent university professors are advising the public to disregard negative test results if you have symptoms. Even the CDC says that negative results only mean that “you probably were not infected at the time your specimen was collected.”

So what does this mean, is the test bad?

Not exactly. In controlled settings, this test is very accurate, which is why the WHO and FDA made it a gold standard for COVID-19 testing. However, certain factors, like timing and the type of specimen, turned out to be much more important than we first thought. Some samples have little or no RNA so the test comes out negative, but it doesn’t accurately depict what's happening in the body. 

So far, most countries are using throat swabs for COVID-19 testing. However, a new study showed that RNA levels decline rapidly in throat swabs, but stay in saliva and anal swabs. Another team of researchers tested saliva from people with negative throat swabs and found that some were positive, including two health workers with no symptoms.

Preliminary results from a study awaiting peer-review say that accuracy of PCR testing was between 74.4 and 88.9 percent when tested from saliva, but less for the nose and throat swabs. These findings are now being further tested, but it might be that we’ve been missing viral RNA because we took the samples from the wrong places.

When it comes to antibody testing, there are even more parameters to consider. The class of antibody you test for depends on what you want to get from the test. A class called immunoglobulin M (IgM) starts secreting earlier than IgG and its detectable on the first day after the onset of symptoms.

Commercially available coronavirus tests, rapid tests, and at-home kits: Where do the WHO and FDA stand on them?

The official agencies including WHO, FDA, and ECDC recommend that only molecular (RT-PCR) tests should be used for a definitive diagnosis of COVID-19. As antibody tests go, the opinions are still divided. Agencies encourage their use and development but add that they shouldn’t be used alone for a diagnosis. None the less, they will be crucial for finding out the true extent of the pandemic and its course. While immunity is not granted, random population antibody testing will likely be used to determine a moment when we can restart our economy. 

These are called serosurveys, and some states are already in the early phase of implementation. New York already state tested  3,000 people and found more positive results than expected (13.9 percent). However, these are early results in a limited population, but the CDC along with FDA is preparing a test for wide-population use that should, according to their website, be ready in late April.

Other than official serological and molecular tests, there are many tests available in private laboratories and since recently a first at-home sample kit.

On February 4, 2020, four days after a public health emergency was declared in the US, the FDA issued a EUA (emergency use authorization) to allow private laboratories to manufacture and distribute tests, providing they meet certain qualifications. These were mainly PCR tests.

Note that these commercially available tests are not tested or reviewed by the FDA. Instead, the FDA  “does not intend to object to the development and distribution by commercial manufacturers”. They are required to inform you that test can give both false positive and false negative results, and shouldn’t be used to confirm or exclude a SARS-CoV-2 virus infection. Some commercial antibody tests can give false-positive results if the person was or is infected with other coronavirus strains, including the common cold.

There are also point-on-care or rapid tests that give results under 30 minutes, and the FDA re-issued a EUA for several of them on March 26. These are based either on finding antibodies (our proteins) to SARS-CoV-2, or proteins from SARS-CoV-2.

While these tests can ease the strain on laboratories that are now working at their maximum capacity, their accuracy is questionable, since there are many cases where the tests haven’t been adequately tested. One preliminary study found that rapid tests can miss as much as 35 to 45 percent of positive cases. In another case, a test made by a manufacturer who claimed 80 percent accuracy was found to be less than 30 percent accurate.

The WHO advises against rapid tests for any clinical-decision making, but if you do decide to get tested, be aware that the result might not be accurate. 

Recently, on April 24, the FDA also approved a first at-home kit for collecting a sample that you can ship to the laboratory, which will then send you your results. The test done in the lab is RT-PCR. If you’re eligible, you can purchase it from LabCorp’s site in the US for $119. At-home kits are also available in Europe.