What do all the initialisms and acronyms mean? What’s the difference between them all? And how do they work? Naomii Seah clears it up.
By now, you may have heard that a “new” type of Covid-19 test is being trialled at Auckland Airport as our border fully reopens to visa-waiver countries.
The Lucira test is a type of self-administered Covid-19 diagnostic test, which utilises the loop-mediated isothermal amplification (LAMP) method. Associate minister for Covid-19 response Ayesha Verrall described it as combining “the speed of a rapid antigen test with the accuracy of a PCR”. The tests will be trialled with 30 Air New Zealand staff for three months. Lucira tests will be cheaper than a PCR ($120-$200 when not publicly funded), but more expensive than available RATs ($6-$7 when not publicly funded); Verrall noted that once the trial is completed, they would likely be useful in certain high-risk contexts such as before commencing essential work, in aged-care facilities and as pre-departure tests.
But what exactly is a LAMP test, and how can a home test be comparable to a PCR, which is conducted in a lab? Why aren’t RATs as accurate as LAMPs or PCR tests? What’s the difference between all these tests? To answer these questions, we first need a quick refresher on PCRs – which were the standard Covid-19 test used in New Zealand until the rollout of RATs in February this year.
How does the PCR work?
Let’s quickly define some terms.
First up: RNA. RNA is a molecule like DNA; they’re both genetic markers. DNA is double-stranded and forms its famous helix shape. RNA is single-stranded. Got that?
Covid-19’s genetic marker is RNA. If Covid-19 RNA is present in a sample, we can say that person is infected with Covid-19.
The issue is that Covid-19 RNA will only be present in trace amounts. Enter PCR, which is a type of “nucleic acid amplification test” – if a person has Covid-19 RNA, a PCR test will replicate that code to measurable levels, confirming infection.
Here’s where it gets a bit complicated. PCR was invented in the 1980s, to replicate DNA – not RNA. PCR stands for “polymerase chain reaction”. A polymerase is the molecule that does the replication. It works by using an existing bit of DNA as a “blueprint”, copying the sequence over and over again. For the polymerase to work, the DNA needs to be split from its double strand into single strands, which is achieved by heat. This means a PCR test needs to be heated, then cooled, then heated, then cooled to achieve the desired DNA replication.
But aren’t we trying to find Covid-19 RNA, I hear you ask? Yes! So to run a PCR test, any Covid-19 RNA in the sample must first undergo a separate reaction to create analogous DNA.
The upshot of all that is that PCR testing for Covid-19 is complicated, requiring multiple steps and heat “cycles” – which is why our testing system broke down as we neared the peak of the omicron outbreak. Advances in PCR also enable us to quantify the starting amount of DNA present in a PCR reaction. In the Covid-19 context, this means PCR enables us to calculate a viral load. It’s a pain in the ass, but it’s accurate. PCRs are no longer the go-to test in New Zealand but still used to confirm infections in people who are particularly vulnerable to becoming seriously ill with Covid, and some countries require a negative pre-departure PCR result for people travelling there.
TLDR: A PCR test confirms Covid-19 infection by replicating and detecting the virus’s genetic material, enabling very accurate diagnosis.
How does a RAT work?
RAT stands for “rapid antigen test”, and they’re actually a type of lateral flow assay. That’s a fancy term for a common type of chemical test. Pregnancy tests are also lateral flow assays, which is why the two look similar; RATs and pregnancy tests operate on the same principles. RATs were rolled out as the standard Covid-19 test in New Zealand in late February as we neared the peak of the omicron outbreak.
So, what’s an antigen? In the context of a Covid-19 test, it’s a unique marker for the virus. Often, that’s a protein on the surface of the virus.
You’ve likely heard the term “antibody” paired with the term antigen. Antibodies are proteins that bind to antigens. Together, they react to create an antigen-antibody complex.
RATs contain specially designed antibodies that will bind to Covid-19 antigens in your snot. If you have Covid, an antigen-antibody complex forms where you drip your sample (taken from your nose with a swab, then mixed with an extraction buffer liquid) on the test. Further along the strip, at the T on your test window, another chemical is waiting that will react with the antibody-antigen complex. If you have a high viral load, ie lots of Covid-19 particles and therefore lots of antibody-antigen complex, there will be a strong coloured line. If you’ve got a low viral load, there’ll be a weak coloured line. If your viral load is too low, you might get a false negative.
As a RAT directly measures the virus in your sample without an amplification step, you’ll need a higher viral load to detect a Covid-19 infection with a RAT than with a PCR.
TLDR: A RAT detects antigens – markers present on the Covid-19 virus itself – so requires more virus particles to detect an infection.
Finally, the question you’ve been waiting for: WTF is a LAMP?
A LAMP test stands for “loop-mediated isothermal amplification”. There’s that word again: “amplification”. It’s another “nucleic acid amplification test” that detects Covid-19 RNA.
Like a PCR test, the LAMP test first needs any Covid-19 RNA present to be converted to analogous DNA before replication. But unlike a PCR, it doesn’t need heat to do it. Instead, through some complicated biochemistry, the whole reaction takes place in one container, and at one temperature, cutting the steps needed and the expertise required for a Covid-19 diagnosis.
For anyone who hasn’t yet seen a Lucira LAMP test, it consists of a tube of liquid into which you put your nasal swab. The tube is then inserted into a single-use battery-powered device that spits out a result within 30 minutes. In simplistic terms, the tube contains all the ingredients needed for DNA replication, and the battery-powered device heats the mixture up to the required temperature. As the reaction occurs, a pH change causes a colour change, which the device monitors. If there’s no Covid-19 RNA in the sample, there will be no reaction and no colour change.
This puts LAMP tests at a similar level of sensitivity to PCR tests, though the device can’t quantify viral load.
LAMPs have been successfully used overseas in countries like Canada and Israel for a while now, causing some to criticise the Ministry of Health and the government for their slow uptake here. The Lucira LAMP tests now on trial with Air New Zealand were given an emergency use authorisation by the FDA all the way back in November 2020. National MP Chris Bishop has been advocating for the adoption of LAMP tests since earlier this year after a meeting with Sir Ian Taylor. Taylor believes the Ministry of Health has been slow to act due to confusion over how LAMPs differed from RATs, telling the Otago Daily Times: “How are the public meant to understand the important difference between a LAMP test and a RAT if the ministry’s officials don’t?”
TLDR: Through some biochemical magic, LAMPs are a user-friendly version of a PCR test, with similar sensitivity, making them more reliable than RATs.