We want technologies that are fast, accurate, high capacity, that do not require expensive and complex laboratory equipment or the expertise of highly trained people, but there is nothing that meets all of those criteria at this time, says Professor Jon Deeks, a biostatistician and evidence expert at the University of Birmingham, UK. “We don’t have any perfect tests like that, but there are some that are good in some ways but not others.”
There are five things to know about coronavirus testing:
PCR and antigen tests are the most common but work differently
While antigen tests look for proteins on the surface of the virus to determine the presence of the pathogen, PCR (polymerase chain reaction) tests are designed to look for genetic material called RNA that instructs the virus to make these proteins.
Both tests also require a swab from the back of the nose or throat as a sample and cannot determine if it is contagious if positive, but that is where the similarities end.
In the case of PCR, the sample is sent to a laboratory where it is heated and cooled with special reagents to convert the RNA of the virus into DNA and then make millions of copies of the DNA, allowing the identification of the organism. This process can take hours, requires sophisticated laboratory equipment and technicians, and typically runs one sample at a time, although there are machines that can process multiple samples. Although the sample must be sent to a laboratory, the time-consuming process is accomplished, as the results are almost 100% accurate at detecting infected people when there is virus on the swab.
In contrast, antigen tests, often called rapid tests, work by mixing the sample with a solution that releases specific viral proteins. Then that combination is applied to a strip of paper containing a custom antibody optimized to bind these proteins if they are present. Like a home pregnancy test, the result is reflected as a band on the paper strip.
The process doesn’t require a lab and can be done in up to 30 minutes, but that speed comes at a cost in sensitivity. Although these tests are reliable when a person has a high viral load, they are much more likely to get false negative results if a person has low amounts of the virus in their body.
Sensitivity and specificity are measures of the usefulness of a test
These two measures are used to determine the credibility of a test: “How well it detects disease and how well it detects the absence of disease,” explained Professor Deeks.
Sensitivity is defined as the proportion of Covid-19 patients who correctly test positive, while specificity is the proportion of patients without an infection that the test correctly identifies as negative.
In general, a highly sensitive test has a low false negative rate, but you risk false positives if its specificity falls short. On the other hand, a very specific test runs the risk of false negatives if the sensitivity of the test is low, but will generally have a low false positive rate. PCR tests are considered the gold standard because they are generally very sensitive and very specific.
When it comes to rapid tests, the person administering the test can be crucial
In the UK, an antigen test called the Innova lateral flow test was piloted in the city of Liverpool as part of the government’s plans to carry out mass vaccinations in the country. The goal was to allow workers to return to offices and allow families to return to hugging loved ones in nursing homes, says Professor Deeks.
But this test-to-enable strategy failed when scientists found that in a population of people with symptoms, the sensitivity of the test dropped to about 58% when administered by self-taught personnel, versus 73% when the test was research nurses. Qualified and 79% when tested by laboratory scientists. In a study that looked at people without symptoms, the sensitivity was reduced to about 49% compared to PCR tests.
“So there is this gradient of saying, the more experience people have in doing the test, the fewer cases they will miss,” he said. There are some stages that need to be followed very carefully, he says, like reading it accurately. “Sometimes it’s hard to tell if that’s a line or if it’s a smudge,” said Professor Deeks.
PCR tests are processed in the lab, so the potential for error is much lower, he adds.
Test makers are also trying to develop tests at home, but given the lessons we’ve already learned about how the accuracy of rapid tests depends on who administers them, that’s a problem, suggests Professor Deeks.
“If people can test more easily, more people will be tested but I don’t think we have the test to do it yet, ” he said. He adds that there are no good studies looking at what benefit this additional test would have – for example, what impact repeated false negative results might have on behavior.
In a proposal for common rules on rapid antigen testing published on December 18, the European Commission said rapid antigen testing should be performed by trained healthcare personnel or other trained operators.
Until rapid tests are more accurate, negative results should not be used to encourage risky activities.
If a test, like the Innova test, is missing up to half of the cases, then no one can be considered free from the risk of having or transmitting an infection, says Professor Deeks.
“There will always be a small percentage of those people who don’t go through all the tests,” said Gary Keating, chief technology officer for HiberGene, an Ireland-based company that has a Covid-19 test. The test uses LAMP technology, which is a low-cost alternative to PCR technology.
“I think it is always dangerous to take a single diagnostic test in isolation and use it as the basis for making a very important medical or lifestyle decision,” Keating said.
If used on a large scale, the results could lead to a false sense of security, according to Professor Deeks.
Governments are interested in using rapid tests, as they are cheaper and faster to implement for mass vaccination campaigns, but because they have limitations in terms of accuracy, it is key not to use negative results to allow more risky activities, like meeting with elderly or vulnerable people. loved ones, he says.
Some countries, such as the United States, recommend getting a PCR test if people with symptoms test negative with a rapid antigen test to confirm the result.
Although rapid tests are good at detecting people who have high viral loads, it is not yet clear what the viral threshold should be to thwart contagion. With Covid-19, those who are infected see a spike in viral load early in the infection, but the viral RNA can linger for weeks or even months.
Antibody tests could be useful to measure the durability of responses to vaccines
Antibodies are soldiers deployed by the immune system in response to a foreign invader, in this case SARS-CoV-2. “At first, there was hope that antibody tests would allow us to diagnose diseases quickly and easily. But it turns out that the tests are not positive for two to four weeks (after infection), “said Professor Deeks.
And the plot thickens, because even if you test positive for antibodies, that information doesn’t tell you much, aside from the high probability that you’ve contracted Covid-19 in the past.
“We really don’t know what levels of antibodies lead to protection (from disease) and, indeed, which type of antibody is the most important – I’m also not sure if there is consensus on that,” he said.
It is also unclear how long Covid-19 antibodies persist in the body, or if someone who has tested positive for the antibody will not contract the virus again.
Where these tests could be useful is to estimate the spread of Covid-19 at the population level, for example what percentage of the population and which ethnic groups have contracted Covid-19, as well as to measure the durability of responses to the vaccine. adds Deeks.
Original article
This article was originally published in Horizon, the EU Research and Innovation Magazine
