The Different Covid-19 Tests and What They Can Reveal: QuickTake

1. What kind of SARS-CoV-2 tests exist?

There are two main types. The first, for diagnosing active infections, typically looks for the presence of the virus in your nose, throat or mouth. The second tests whether you have any immunity to the virus, either from a previous infection or from a vaccination. Typically these are antibody tests, which look for evidence, generally from a blood sample, that your immune system has built up antibodies to fight off the virus.

2. How do tests detect active infections?

There are several ways, but the gold standard — at least in terms of accuracy — is the so-called molecular test. These tests dominated the public discussion last year, especially when few places had enough of them to determine how widely the virus had spread. They work by looking for bits of the virus’s nucleic acids, or its genetic material, in a sample of secretions. Once scientists have sequenced a newly discovered virus’s genome, they can develop these highly specific tests within a couple of days, which is a great asset early in an outbreak.

3. What are the downsides to molecular tests?

Molecular tests typically require several components, including chemical reagents, small plastic containers and swabs. One widely used type relies on trained lab technicians to perform a complicated process called reverse transcription polymerase chain reaction (RT-PCR), which amplifies the virus’s genetic material so that it can be studied in detail. A lack of components, machinery or technicians can limit the availability of tests. Testing saliva eliminates the need for a swab, though some studies suggest this approach picks up fewer cases. While some molecular tests can churn out results in 30 minutes or less, they don’t scale very well. So scientists often use mechanized systems, such as one from Roche Holding AG, which can take a few hours to produce results but, in optimal circumstances, can handle thousands of tests a day.

4. Can we rely on these tests alone for detecting cases?

No. Given the logistics of collecting samples and sending them to labs, many of which have been overwhelmed, it’s still common in some places for people to wait several days to more than a week for results. That’s too long in the face of a virus that people often spread to others before they feel ill, or without ever experiencing symptoms. To break chains of transmission, it’s essential to catch infections fast and early, so that someone who tests positive can isolate from others and public-health officials can warn those who were recently in contact with that person to test and quarantine as well. While alternative forms of molecular tests with quick turnaround times — including one called RT-LAMP and another based on the gene-editing tool Crispr — could alleviate some of these challenges, these versions aren’t widely available.

5. Is there a simpler way to diagnose?

Yes. Countries are increasingly embracing faster, cheaper and more accessible tools called rapid antigen tests — some of which people can perform at home. Often, these are lateral flow tools, which are similar to home pregnancy tests that run a liquid sample over a reactive surface. A kit, which can cost less than $5, includes a swab, a tiny bit of solution, and a small plastic tray containing antibodies resembling those that a person’s immune system would activate to fight off SARS-CoV-2. The test-taker gets a sample from his or her nose or throat, dips it in the solution, and puts a few drops in the tray. If the person is infected, the antibodies will bind to proteins in the virus that are present in the sample. This will prompt a line to appear on the plastic tray — or some other indication, depending on the test — signifying an infection.

6. How accurate are rapid antigen tests?

Early on in the pandemic, rapid antigen tests got a bad reputation because versions rushed to market proved to be highly unreliable. Over the course of the year, though, far more accurate versions have become available. While they’ll probably never be as sensitive as molecular tests in finding evidence of an infection, they compensate for that with their speed and accessibility. In a pilot study in Liverpool, England in late 2020, rapid antigen tests identified nearly 900 people who didn’t realize they had a SARS-CoV-2 infection — and presumably wouldn’t have otherwise received a test. Some critics pointed out that these tests missed many infections that molecular tests would have caught, and they can return false positives. Supporters argued that the early detection that did happen allowed for a lot of self-isolation and contact tracing that otherwise wouldn’t have occurred. For these tests to really thrive, people may need to perform them regularly. If one test fails to catch an infection, it’s highly unlikely that repeated tests will make the same error. While the take-home versions involve several steps, they’re generally no more complicated than, say, pumping gas into a car. And many experts say the reliability improves after someone has tried them a couple of times.

7. Is being less sensitive all bad?

There is a potential upside. Molecular tests are so sensitive they sometimes flag people as infected who’ve basically already recovered — and who have so little virus in their systems, they’re no longer contagious. Rapid antigen tests are thought to be better at identifying people who are actually infectious, so that people aren’t forced into self-isolation for longer than is really necessary.

8. What about variants? How do we keep track of them?

Because the virus constantly mutates, health officials need to watch out for new variants of concern — like the more infectious strains that were first identified in the U.K., South Africa and Brazil. The best way to identify such lineages and monitor their spread is to take samples from infected people and sequence the genome of the entire virus or at least the spike protein that gives it its crown-like appearance. That, however, can be expensive and time-consuming. As a shortcut, researchers use other techniques, such as subjecting samples to molecular tests that have been slightly tweaked to identify specific mutations. That helps get a faster and fuller picture of what virus strains are fueling a region’s outbreak, though it’s important for researchers to confirm some of those results with genetic sequencing.

9. What about antibody tests? How do they work?

A person infected by a virus or vaccinated against it summons antibodies designed specifically, like keys for a particular door, to latch onto and neutralize the proteins that form the bulk of that particular virus. These antibodies can linger for months — or even years in some cases. To make antibody tests, developers either grow in a lab — or buy from a supplier — copies of proteins that appear naturally on a particular virus. If a person has already fought off the virus or been inoculated against it, their blood should contain antibodies that will latch onto these proteins in the test. To be useful, the tests need to be highly specific, so a positive result isn’t triggered by similarly shaped antibodies that once fought off, say, a related but different coronavirus that causes the common cold.

10. Why are antibody tests important?

To end the pandemic, we need to build up our collective immunity. It’s unclear how long protection against reinfection lasts for people who’ve recovered from a SARS-CoV-2 infection or how long the immunity provided by Covid vaccines will last, especially in the face of new viral variants. While the earliest SARS-CoV-2 antibody tests indicated whether someone had any protection against the virus, more recent versions actually quantify the level of antibodies — and, used repeatedly, can show if levels are dropping. That could help determine who needs to receive a booster shot of a vaccine at some point. For scientists and policy makers, antibody tests are also a powerful tool to understand how widely the virus has spread in a region, which can shine light on which public health measures have worked and which haven’t. And for individuals who never tested positive for the virus but think they may have had it, these tests provide a way to look back to see if they may have some protection — even if they haven’t been vaccinated.

11. What are the drawbacks?

Scientists are still investigating what level of antibodies is needed for someone to be protected against future SARS-CoV-2 infection — a factor that could play into how often people receive booster shots one day. Nor is it clear how much T cells, another weapon in the immune system, can provide protection if antibody levels drop. But that could begin to change, as tests designed to detect T cells against the coronavirus are starting to become more widely available.

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