What follows comes from a recent post by Dylan Morris, a postdoctoral researcher in ecology and evolutionary biology at UCLA, who has become a leading voice on such matters during the pandemic.
PCR tests (aka “molecular tests” and “RT-PCR tests”)
How they work: Identify pieces of SARS-CoV-2 RNA (the virus’ genetic material) present in a sample taken from your nose or throat. They do this by subjecting the sample to a chemical process that will copy pieces of virus RNA, and then repeatedly copy those copies—provided those pieces are initially present to be copied in the first place. This chain reaction gives the process its name; “PCR” stands for “polymerase chain reaction.” If, at the end, you have a bunch of copies (there are multiple ways to quantify this), it’s clear that there was SARS-CoV-2 RNA in the original sample.
Strengths: extremely sensitive at detecting whether you’re currently infected or recently were infected. Even a small bit of RNA can be “amplified” through this repeat-copying chain reaction.
Weaknesses: slow, expensive, labor-intensive. If labs are overwhelmed or inefficient, you may get results days after your sample was taken.
What a result means/doesn’t mean: If you are positive, you almost certainly were currently or recently infected with the virus when the sample was taken. If you are negative, you may not have been. But you also might have been too early in the infection to have detectable virus in your nose or throat. So a negative on a PCR from a swab taken even 24 hours ago is no guarantee that you are not “currently infectious.” In other words, PCR is great for diagnosis, but not great for public health unless the turnaround is very fast.
Antigen tests (aka “rapid tests” and “lateral flow tests (LFTs).”
Not to be confused with: “rapid PCR” (an expedited PCR test), antibody tests, or lateral flow tests used for other purposes (such as detecting antibodies).
How they work: detect a piece (“antigen”) of a SARS-CoV-2 virus particle (“virion”) in a sample taken from your nose or throat. They do this in a variety of means. A common one is by using antibodies that bind to the target antigen. If binding is observed, the antigen is present. If it’s not, the antigen is probably absent.
Strengths: Fast! Results in as little as 10-15 minutes from the sample collection. Some (particularly lateral flow tests) can be mass manufactured, sold cheaply or distributed for free, and performed at home. Somewhat to very good at detecting virus when people are “currently infectious.”
Weaknesses: some false negatives, particularly when people are already PCR positive but not yet infectious, but even (and, it seems, especially for vaccinated people with Omicron) early in the infectious period.
What a result means/doesn’t mean: If positive, you’re almost certainly either currently infectious or were recently infectious. There are some false positives, but not many. If positive and asymptomatic, assume you have it but maybe consider a confirmatory PCR. If positive and symptomatic, assume you have it. If negative, you probably aren’t currently infectious, but might not stay that way. If you want to use testing to reduce the chance you’ll infect a vulnerable person at an indoor gathering, take the sample as close as possible to the start of the gathering–as in literally at the door, if possible. Rule of thumb: a fresh uncertain negative beats a stale certain negative. Usage tip: for self-swab tests, swab the back of your throat as well as your nose, even if the test only says to swab your nose. Will not hurt and may reduce the false negative rate.
Nucleic acid amplification tests (aka NAATs)
How they work: Identify pieces of SARS-CoV-2 RNA (the virus’s genetic material) present in a sample taken from your nose or throat. Like PCR, they do this by making copies of the RNA. In fact, PCR is, strictly speaking, a kind of NAAT. The difference is that there are a number of alternative methods suitable for more rapid results or at-home testing.
Strengths and weaknesses: These alternative NAATs are sort of a middle ground between PCR and antigen tests. They may be better at detecting small amounts of virus than some antigen tests, but may be less so than a proper lab PCR (though there’s variation!). Non-PCR NAATs are typically faster than lab-based PCR, but more expensive than antigen tests.
What results mean for you: consider a rapid NAAT result as a more fresh but perhaps less certain version of a PCR result.
Antibody tests (aka serology/serologic tests, including ELISAs)
How they work: Detect antibodies against the coronavirus generated by prior infection and/or vaccination. NOTE: these do NOT tell you whether you are currently. Some may be useful for determining whether you were recently infected, but their primary uses are answering one or both of two questions:
- a) were you unknowingly infected at some point in the past?
- b) did you mount a protective response to vaccination?
What results mean: Vaccines work by teaching your body to make antibodies targeting the virus spike protein. Tests that detect these anti-spike (“anti-S”) antibodies will tell you whether you mounted an antibody response to vaccination, but for that same reason they can’t determine whether a successfully vaccinated person was also previously infected. For that, you need a test that can detect anti-nucleocapsid (“anti-N”) antibodies, since most vaccines do not teach your body how to make anti-N antibodies. Exceptions are “whole virus” vaccines like Sinovac Coronavac, Sinopharm, and COVAXIN. People who had these vaccines will not be able to use an anti-N test to assess prior infection. Also, most antibody tests are qualitative: they give you a yes/no answer on whether you have anti-S and/or anti-N antibodies, but not how many you have/how good they are. If you’re in a vulnerable group and want to assess the strength of your antibody response (so that you can get an additional booster if needed), you’ll need to order a quantitative antibody test, which gives you an approximate measure of this.