The imperative to “test, test, test” has become a slogan for the coronavirus pandemic since it was voiced last month by Tedros Adhanom Ghebreyesus, head of the World Health Organization. But the simple goal continues to elude wealthy nations struggling to keep up with the spread of the virus among their populations.
Germany and South Korea led the way with large-scale testing, but the United Kingdom and the United States have lagged behind. The longer the delay, the greater the uncertainty about the size of the viral threat. As the hunger for diagnosis increases, the test kits are rejected and the impatience with government supports is great, we examine the available technologies, their potential and their limits.
What tests are available for coronavirus infection?
There are two main types. The first, an antigen test, detects the presence or absence in the body of the new coronavirus, which causes Covid-19 disease. The second, an antibody test, looks for signs that someone has been infected in the past by looking for an immune response.
Since Chinese scientists released the full genetic code for the virus in mid-January – officially known as Sars-CoV-2 – laboratories around the world have been able to use antigen tests to identify its genes in patient samples. They use a procedure called polymerase chain reaction (PCR) which has been common practice in laboratories for 30 years.
PCR samples can come from several different sites in the patient. The simplest is the nasal swab taken well inside the nose. The back of the throat is another option. For hospitalized patients, a sample of the lower respiratory tract may give the best results. The antigen test reveals whether a person has a current infection and could therefore pass Covid-19 to others.
In contrast, antibody (or serological) tests work on blood samples to detect the immunity conferred by a past infection. The test kits use virus proteins as a “glue” to trap antibodies in the blood, said Eleanor Riley, professor of immunology at the University of Edinburgh.
A finger prick should provide enough blood to detect two types of antibodies against Sars-CoV-2. The former, IgM antibodies, are short-lived and may indicate that the virus is still present. They usually go away a few weeks after infection. In their place, a second, more durable type is emerging, IgG antibodies. No one knows yet how long they will last and offer resistance to reinfection – something from a few months to a few years seems possible.
Antibody tests are prioritized by governments, including the United Kingdom and Germany, as they will be essential in informing individuals if they can return to mix safely in society without transmitting or catching an infection. When performed in a representative sample of the population, they will also answer key epidemiological questions – including the number of people infected with mild or no symptoms.
Once developed, antibody tests are expected to yield results faster than traditional PCR tests, taking a few minutes rather than a few hours, although much faster antigen kits are under development.
Who does the tests?
When health officials began to realize that the coronavirus epidemic could pose a global threat, they began to develop tests in government laboratories such as those operated by the United States Centers for Disease Control and Prevention (CDC) -United States and Public Health England, who already had extensive experience in using PCR technology for diagnosis.
Traditionally, the diagnosis of antigen has mainly been in the public sector, with private companies providing test components such as chemical reagents and swabs for patient samples – some of which have been rare. But in recent weeks, there has been a huge mobilization of private sector resources as companies around the world rush to enter a growing market, deploying automated PCR kits that process samples much faster than laboratories conventional.
New antigen tests are relatively easy to create because “the PCR test is a small addition to an existing test,” said James Gill, clinical professor at Warwick Medical School.
But antibody tests take longer to develop because they have to be created from scratch. “You had to physically get the patient’s blood, find the antibodies in that blood (molecules smaller than the virus), create a reproducible antibody in the laboratory, and then create a reagent test that will react in the presence of this antibody – which can be read by health care teams, ”said Dr. Gill.
The private sector has played an inordinate role in the development and manufacture of antibody tests, although its products have yet to be validated by public health authorities before use.
The presence of Chinese companies has stood out in efforts to increase the supply of both types of tests. Of 202 companies worldwide that produce Covid-19 test kits on the market, 92 are from China, where the outbreak was born and where an innovative medical technology sector is booming.
According to data from the Foundation for Innovative New Diagnostics (Find), a Geneva-based nonprofit group that tracks product development, the second largest number of coronavirus testing companies is in the United States, with 29.
The search list is not exhaustive and does not include certain major players who have not sought to appear. Among them, Hologic, listed on the Nasdaq, whose test has been authorized by the United States Food and Drug Administration for emergency use.
Beyond conventional antibody and antigen testing, researchers at universities and biotechnology companies are developing imaginative new diagnostic technologies. For example, Crispr, a gene editing technique that has taken the biotechnology world by storm, can be adapted to recognize and cut specific genetic sequences in Sars-CoV-2, which can then be identified via changes in color.
How quickly are the tests deployed?
Very unevenly – and not fast enough in many countries. Although there is no formal centralized database, Find has collected data indicating that a cumulative total of more than 4.9 million tests had been performed worldwide as of March 29. But this figure excludes China because the group could only obtain reliable data for one Chinese province.
South Korea, the country that started first with extensive Covid-19 testing, has so far achieved 394,000 (or 770 per 100,000 people). Iceland has performed 4,160 tests per 100,000.
The United States was very slow to start because the CDC’s first test did not work well, so it had to go back to the drawing board to create a new one. It then took time to allow other laboratories to test Covid-19. But in the past two weeks, the United States has accelerated testing quickly.
Among the major European countries, the champion appears to be Germany, where public health officials have estimated that laboratories perform up to 500,000 coronavirus tests per week. Although official data has yet to confirm this number, this suggests that testing capacity has increased rapidly in recent weeks. The decentralized testing and laboratory infrastructure in Germany means that work is carried out not only in hospitals and doctors’ offices, but also in special docking stations.
Manufacturers are ready to provide the world with millions of antibody tests, but health and regulatory authorities always assess their accuracy before allowing large-scale deployment. Last week, British Secretary of Health Matt Hancock announced that the country had ordered 3.5m antibody test kits from various manufacturers.
How reliable are the tests?
The PCR test is extremely accurate when performed with care by experienced technicians in a well-equipped laboratory. Because it specifically detects genes found only in the Sars-CoV-2 virus, it will produce very few false positives, said Andrew Preston, reader in microbial pathogenesis at the University of Bath.
False negatives – which mistakenly indicate that a person is free from infection – are more of a problem. They often result from problems in collecting and processing patient samples. For other viruses, false negative rates of 10% are widely accepted and can reach 30%. Therefore, PCR tests “were more often used to confirm an infection rather than giving everyone certainty,” said Dr. Gill at Warwick Medical School.
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The accuracy and reliability of the new antibody tests will not be known until they have been validated and the technicians have acquired more operational experience.
The Spanish health ministry last week withdrew 8,000 Chinese-made test kits delivered to the Madrid regional government due to concerns about inaccurate results. But manufacturer Shenzhen Bioeasy said the problems may have been due to sample collection or improper use of the product.
Dr. Preston said, “It is not easy to quickly and massively increase testing capacity when it requires both high-quality kits and properly trained staff.”
Additional reporting by Donato Paolo Mancini and Tobias Buck