A rapid test that detects coronavirus variants with dangerous mutations could be used to tell people which variant of the virus they are carrying.
The test could also dramatically improve surveillance efforts around the world, boosting the chances of containing new variants before they spread widely.
The new method of detection, developed by Stephanie Oerum at Novozymes in Denmark and colleagues, requires only a small tweak to the PCR tests already widely used around the world to detect the coronavirus. It will be made available on a non-profit basis.
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The test can reveal if the virus infecting someone has one or more of the key mutations that characterise variants of concern. 鈥淲hen you give them the result, you could say, 鈥榶es, you are positive for coronavirus and you carry a problematic variant鈥�,鈥� says Astrid Iversen at the University of Oxford, who is collaborating with Novozymes.
The hope is that these people will then take extra care to avoid infecting others, and can also be prioritised by track and trace officials.
鈥淭his is something that is badly needed,鈥� says Iversen. 鈥淔or track and trace, as soon as you know a person is positive you need to know if they carry a problematic variant, to stop that variant spreading in the community.鈥�
At present, the only reliable way to detect variants is to sequence the entire 30,000-letter-long genome of the SARS-CoV-2 virus, which is expensive and slow. It takes around a week in the UK, according to Nick Loman at the University of Birmingham, who is part of the Covid-19 Genomics UK Consortium doing the sequencing. 鈥淎 week is both incredibly impressive and too long,鈥� he said during a press briefing on 9 February.
The UK has been sequencing more samples than any other country, and recently increased its efforts even further. But it is still sequencing just 15 per cent of positive tests, meaning it may be missing most cases. Most other countries do far less sequencing, and therefore know little about which variants are circulating.
PCR tests are cheaper and quicker than sequencing. The process takes just hours, though it can take days for people to receive their results.
PCR tests work by looking for short sequences 鈥� around 20 letters long 鈥� specific to the SARS-CoV-2 genome. A 鈥減rimer鈥� matching each target sequence is added to a sample, kick-starting an easily detectable chain reaction if it binds to the target sequence. It is usual to look for three sequences to improve reliability.
It is possible to use PCR tests to detect large mutations, because a big mutation in a target sequence stops the primer binding. In this case, a test will come back positive for just two out of the three target sequences.
By chance, some PCR tests were able to detect the B.1.1.7 variant in the UK, because this variant has a deletion that just happens to be in one of the target sequences. This has been extremely valuable, allowing researchers to see early on that it spreads faster, and also revealing that it is somewhat deadlier.
However, most coronavirus mutations, such as the E484K mutation that helps variants seen in South Africa and Brazil evade immunity, involve one letter changing into another, which isn鈥檛 enough to stop the primer binding and therefore cannot be detected by standard PCR tests.
Oerum and her team鈥檚 method involves doing an extra PCR test on a sample. In the extra test, a bit of artificial DNA, or 鈥渙bligonucleotide鈥�, that binds especially tightly to a mutant target sequence is added in addition to a primer matching the non-mutant sequence. If the mutation is present, this changes the result.
This extra step takes just half an hour longer than usual, she says. The main disadvantage is that doing an extra test means that labs won鈥檛 be able to do as many normal tests as usual.
Initial studies suggest the method is highly accurate. The team is now confirming this by testing already-sequenced samples. This process should be complete in a week or so, after which the team will publish the full protocol.
Novozymes isn鈥檛 a diagnostic company and won鈥檛 seek any financial benefit, says its chief science officer, . 鈥淚t鈥檚 really something we do just to help,鈥� he says. 鈥淲e just want to get this out as widely as possible.鈥�
It is likely that many other groups are working on similar approaches. Public Heath England has said it is working with commercial partners to develop PCR-based tests for variants, but didn鈥檛 respond to a request for more details.
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