Do antibody tests fulfill the promise of unlocking lockdowns? | World News

AhThe Erasmus University Medical Center in Rotterdam, Marion Coupmans, and a team of scientists have gone through a tedious process to validate the Covid-19 antibody test. Over the past two months, dozens of positive tests have been on the market. Biological tests rarely give such weight, as many governments want the results of large-scale tests to be reflected in their decision to end lockdown.

Most tests are sold enthusiastically and boast the ability to accurately detect if someone has been previously infected with the Sars-CoV-2 virus. The painstaking task of demonstrating whether the test does what they say fell into a worldwide network of 12 independent centers, one of which is the Koopmans team.

“We’re currently offering over 200 tests, and that number is growing daily,” she says. “People want to run tests quickly, so there’s this large, almost aggressive marketing of test kits, and a lot of promises, but no proper research. “

NHS doctors use a diagnosis called the polymerase chain reaction (PCR) test to detect traces of viral genetic material from oral or nasal swabs and identify suspected cases of Covid-19. However, the PCR test only works if the virus is still present in the body.

The purpose of using an antibody test is to do what is known as serosurveillance or serodiagnosis. This means testing a sample of the population to get an indication of the prevalence of Covid-19 infections, including those who are asymptomatic or have only mild symptoms.

Antibody tests look for Y-proteins produced by the body in response to an infection that remains in the blood (and sometimes permanently) for some time after recovery.

Policy makers hope to have an accurate model of how far the epidemic has spread, and what the tally of real infectious diseases is. This topic has become hotter in recent weeks. At the beginning of April, Bruce Aylward, a World Health Organization representative who evaluated China’s response to the outbreak, saidThe tip of a magnificent iceberg“And he suggested that the virus affected only a few communities. He cited a study conducted in Guangdong Province, where 320,000 swab samples were retested with Covid-19 and were less than 0.5% positive.

Jay Batacharya, a professor at Stanford University in California, also said that Covid-19 had a relatively low prevalence after testing for antibodies in 3,330 people in one of the first sero-studies, Santa Clara. Detected rate. Battachariya Up to 4%, But then his work has been criticized by other scientists for various reasons, especially since then It appeared His wife recruited some of the research participants by sending an email to a local high school.

Other early serological surveys conducted in New York City And the German town Gangert We have found much higher prevalence, ranging from 14-21%. However, these communities have been particularly severely affected, and views have been expressed as to whether the entire community represents the population.

Obtaining accurate antibody data is also essential for vaccine developers to ensure that their products perform as intended during clinical trials. The results of serodiagnosis will ultimately help determine if exposure to Covid-19 provides immunity or faces the seasonal wave of infection. And, interestingly, they may help determine the importance of pre-existing immunity. Scientist already has I wondered Whether the difference in mortality between different countries is due to specific populations that have been exposed to similar viruses in the past.

However, to collect truly reliable information, it is necessary to show that the antibody test used has a high degree of accuracy.

Strict verification
The majority of current antibody tests target spike proteins. It is the only protein on the viral surface that causes entry into the host cell and is the major part of the virus that elicits an antibody response. However, in the amino acid structure of spike protein 60% overlap With four seasonal coronaviruses circulating in humans. Targeting the wrong part of this protein means that antibody tests can’t distinguish between those who have Covid-19 and those who have a common cold.

Scientists first examine the specificity of the test, the percentage of healthy people who were correctly identified as free of the virus, using blood samples from healthy people taken before the outbreak began.

The specificity must be close to 100% to use the test. For example, if 5% of the population has Covid-19, a test with only 90% specificity will falsely evaluate 95 people with the virus in a sample of 1000. In other words, nearly 70% of positive results are false.

If the specificity of the test is sufficient, scientists will begin investigating its sensitivity (the percentage of people correctly identified as having Covid-19 in the last few months) and determine the difficulty of the process. Steadily increase. To fully assess this, they use samples from people who have experienced severe bouts of illness, followed by samples from people who are mildly affected.

However, such verification was time consuming, and there was growing concern about the economic consequences of prolonged blockades, which made some countries impatient. The UK Government wants the public to conduct their own tests through the fingerprick kits, which are available to millions. Amazon or boots In the coming weeks.

But these plans last month, Fourm antibody test Purchased from China at a cost of £ 16m, scientists at Oxford University have found that both sensitivity and specificity are insufficient for high-volume use. Currently, up to 17.5 million tests have been provisionally ordered from companies in the UK.

2 companies last week, Roche And Quotient, announcement They have US and EU approval of antibody tests with 100% sensitivity and 99.8% specificity-but both of these tests must be analyzed in the laboratory under medical supervision. Requires a blood sample taken.

Lessons from HIV
Lessons from past outbreaks have shown that rushing large epidemiologic projects is unwise. Such initiatives need to be properly planned to collect reliable data.

The only comparable serologic survey of this size was for HIV in the 1980s. One of the pioneers of these serologic studies throughout the United States was James Curran, now a Professor of Epidemiology at Emory University. One of the lessons learned from this experience, according to Curran, is that serology is most useful when targeting specific populations, and Covid-19 is targeted at health care workers, home caregivers, or It is meant that priority groups such as schoolchildren should be targeted to obtain information that can be used to make public safety decisions.

“It is very important to do a systematic investigation to find out which parts of a particular population are infected or not, and we do it for the highest priority groups.” He says “The danger is that we’ll let everyone escape to take the test, and then we need to retrospectively determine how representative they are.”

Karan emphasizes the example of elementary school children who seem to have been largely unaffected by Covid-19 to date. “We know that children are very efficient carriers of the influenza virus when they get sick,” he says. “The same thing with coronaviruses? Before we get back into school, we need to know that. They may not be at high risk of dying, but they may be great at transmitting. It is really important to know the past history of the virus in children of different ages. ”

Does it prove immunity?
One of the hopes of an antibody test is to show whether people infected with the virus have some immunity and allow the government to distribute “immune passports” that allow people to return to work.

But so far, it is unclear whether those who have recovered from Covid-19 actually have so-called neutralizing antibodies, and whether they bind to the virus and block future infections. The question remains as to whether such antibodies will last a lifetime or decline over months or years.

“It’s important to answer this question regarding vaccine success,” said Elitza Theel, head of clinical microbiology at the Mayo Clinic in Rochester, Minnesota. “Is there a single vaccine, or is it like the flu that needs to be boosted and vaccinated each year?”

Immunity to pathogens ranges from varicella-zoster virus (which causes varicella) to HIV, where antibodies provide lifelong protection, where HIV is a non-neutralizing antibody in which infected individuals do nothing to clear the disease. Produces.

So far, the only hint as to where Covid-19 lies in this spectrum comes from research in China. Recent survey 175 patients In Shanghai, those who were severely afflicted with the virus produced large amounts of antibodies, while those who had only mild seizures produced much lower levels. This suggests that those who are severely afflicted with Covid-19 may be protected from reinfection for some time, but immunologists have confirmed that they are neutralizing antibodies. Still trying to confirm.

“The expectation is that there is at least partial short-term immunity, but we certainly don’t know that. We also don’t know if a mildly infected patient has some immunity.” Said Theel. “For those with a short illness, it is possible that the body immediately killed the virus before it had time to mount an antibody response.”

It will take some time to comprehensively evaluate the antibody test results and confirm the level of immunity to Covid-19. People need to be tested many times over the months and years to see if the antibodies to the virus remain in the blood at high enough levels. As a result, many scientists believe that the government must make a decision assuming that it will not be possible to distribute immunity passports in the near future.

Koopmans believes a pragmatic solution is for governments to re-establish a society with infrastructure and prepare for hundreds of thousands of ongoing swab tests. These can be used to monitor the number of new people infected and whether there is a second, third or fourth peak risk.

“Everything needs to be up and running,” she says. “We regularly inspect swabs to keep an eye on health care workers, teachers, and even sampling of domestic effluent to detect signs of the virus. After that, if virus circulation resumes, , You can pick it up as soon as possible. “