When it comes to halting the Covid-19 crisis, virus testing is key for diagnosing and for tracking the epidemic. It’s the only way to uncover just how many people have been infected, or could infect others.
Despite how crucial testing is, some countries have far more tests than others – and that testing isn’t available to everyone. The reason comes down to several factors, including timing, logistics, and the complexity of collecting samples, obtaining the raw materials and equipment for testing, and having the expertise to do the tests accurately.
The countries that acted swiftest in terms of testing have also been among the largest successes of the virus’s containment. Take South Korea, which began testing early in clinics, hospitals and drive-through centers. Its first confirmed case was on 20 January 2020. Six weeks later, on 16 March, South Korea was testing 2.13 people per 1,000. Italy, on the other hand, which had its first confirmed case on 31 January, was testing 1.65 people per 1,000 six weeks on. Even while Italy ramped up its numbers significantly – it is now testing a far higher percentage of its population than South Korea, at 24.5 people per 1,000 compared to South Korea’s 11 – the slower start was one factor that made it harder to contain infections overall. (Figures range elsewhere: Spain is currently testing 20 people per 1,000, Australia 17, Canada 15, the US 12 and the UK six.)
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Starting testing later often meant the virus had chance to spread through whole communities by the time testing was implemented. Then came simple economics: as demand spiked, supplies were drained. The countries that reacted slowly required more tests to identify many more infections as a result.
Testing alone does not cause declines in disease. There are still questions about how reliable test results are for people who are asymptomatic, for example. And the biggest strides have been seen in countries that combined testing with contact tracing and containment measures. Even so, testing allows public health authorities to gather data to make appropriate policy decisions – including about whether more selective or stricter social distancing policies are necessary.
Why ramping up testing is so difficult
Lagging countries are still trying to increase testing capacity. In early April 2020, for example, the UK Health Secretary announced an initiative to scale up to 100,000 tests a day by the end of April, a ten-fold leap from 10,000 a day at the end of March.
But when it comes to Covid-19 tests, scaling up by factors of 10 or 100 is not as simple as stocking up when emergency hits.
That’s because the process of accurate Covid-19 testing requires coordination of a number of processes. First, you must acquire the test kits – the long nasal swabs and chemicals required to process them. These are then sent to expertly-trained laboratory technicians who analyse the samples using a PCR machine, which can be laborious. And finally, there needs to be a system to accept samples and report results to the right people.
Laboratories that were previously doing research only (as opposed to testing for patient care) not only have to run tests accurately – they also have to implement new computer and administrative systems to collect patient information and then to distribute the results back to the health care providers.
Making matters more complicated, many countries, including the UK and the US, have had problems getting enough supplies for testing. It’s not so much a matter of lacking the raw materials but making sure they are pure and mixed in the right amounts. Each brand of test has their own unique blend of about 20 chemicals. Each set requires its own unique packaging. Roche reagents don’t fit a Cepheid any better than a Chevy truck part fits a Prius. Making test kits is as burdensome as drug-making.
In addition to chemicals, many laboratories lack the government-approved machines. In the US and South Korea, laboratories were allowed to file a so-called Emergency Use Authorisation application. This lets labs develop their own tests based on government protocols, but tweak them according to equipment.
As a general rule, the easier a test is to perform, the harder it is to manufacture. The first Covid-19 tests were simple to make but required specialised expertise. Many early tests take about four hours – two hours of hands-on work, two hours in the machines. Roche and Abbot instruments, available in some academic laboratories, can run 80 to 100 samples at a time. They’re partially automated but still require skilled technicians. Simpler tests that smaller hospital labs can run are hitting the market, but availability is sparse.
Once a laboratory is set up and tests procured, the process can begin – starting with the pre-test.
The pre-test begins with a nasal swab. This is not an ordinary cotton ear-bud but a long, skinny stick that is flexible enough to extend to the ear. The swab is nylon or foam, not cotton, which inhibits the test.
Even procuring those swabs has been difficult thanks to the crisis. Copan Diagnostics Inc, based in northern Italy, had to receive special government permission to continue production despite the Covid-19 lockdown. Puritan Medical Products, based in Maine, suffered labour shortages.
As a result, nasal swabs are now precious. A few entrepreneurs are trying to make more with 3D printing, but there have been teething problems, as with any brand new technology. And the vendors are charging 10 times or more what swabs used to cost.
Once the swab gets to the laboratory, a highly-skilled laboratory technician, wearing the same protective clothing as nurses and doctors, places it into a biosafety hazard box – a glass box with controlled air flow to prevent the virus from escaping.
The process is dangerous. Laboratory work generates droplets. Just one droplet may contain a million or so viruses that can contaminate the laboratory worker or the laboratory. It can also land in another sample. If that happened, a patient who didn’t have Covid-19 would be told they did.
Laboratory directors love the cooking metaphor. Running a lab test, they say, requires a chef’s attention to detail, measuring precisely each ingredient at the right time, in the right order and at the right temperature. But unlike cooking – where a little bit of extra spice here or there may enhance the final product, or at worst case ruin the flavour – a faulty lab test can produce deadly results.
“One hiccup throws everything off,” said Dr. Kimberle Chapin, professor of pathology, laboratory medicine, and medicine, at the Warren Alpert School of Medicine at Brown University and director of microbiology for the Lifespan Academic Medical Center, Rhode Island.
Expert technicians with the meticulous skill to run the test are a scarce commodity in many countries.
The testing phase
The testing phase requires two crucial steps. First, extraction – retrieving the potential virus from the muck of the mucus on the swab, and second, detection.
With garbed arms, technologists manipulate samples into tubes to be loaded onto an instrument where chemicals break open the viral coat (the “crown” of the coronavirus), and isolate the pure RNA, a single strand of genetic material.
Next, they pipette the RNA into a disc with tiny wells. Each has the reagent that hunts for particular pieces of the Covid-19 viral genome.
The discs are taken to a machine where chemicals multiply short pieces of the viral genome about a billion times. These short pieces are then detected by a fluorescent probe that glows if Covid-19 is there.
If the patient’s sample did not have the virus, then nothing happens. No multiplication. No glow.
The technologist then checks the controls (the known positive and negative samples that prove the run worked), enters the results into the computer, and calls in the results.
The only thing worse than no test is a test that’s wrong. Laboratories can only start testing patients after they have done sufficient studies to ensure reliability. These tests usually take upwards of six weeks, but technicians have been working double shifts to speed the process.
To make matters more complicated, sometimes a patient can test negative even when they’re sick. They may have the virus in their lungs, but no longer release it near the nose where it would stick to the swab. Or, the sample was not obtained correctly.
Of course, this all describes swabbing as a means of searching for a live virus in the patient.
But the latest buzz in testing is the blood test: the antibody or serology test, which could be used to establish if someone had the disease in the past and developed immune cells to recover from it. It detects one specific part of a patient’s immune response to the disease – the presence of antibodies. It is hoped these proteins might protect patients from reinfection, although any protection remains to be seen.
Devising an accurate antibody test ushers in a whole new set of challenges. It must ensure that it’s spotting the precise immune cells that fought this particular germ, and not some run-of-the-mill coronavirus, like the common cold. And some people might recover from the disease without ever developing antibodies.
Even then, we do not know enough about Covid-19 yet to know if infected patients are no longer susceptible. (Read more about whether you can get Covid-19 twice). Nor are there any proven, reliable antibody tests. The UK bought millions of antibody tests that didn’t work.
If we have learned anything so far, it’s this: we can no longer ignore the warnings of infectious disease experts who, for decades, have been calling for global preparedness for the inevitable new, dangerous viruses. One part of this preparation includes a worldwide system to rapidly develop, prove, and distribute tests for a new virus as soon as possible after it strikes.
Now more than ever, we rely on the dedicated laboratory workers most of us will never see and yet are crucial members of the first-responder teams.
Sheldon Campbell, MD, PhD is a professor of laboratory medicine at Yale and associate chief for the clinical laboratories for the VA Connecticut Healthcare System. Randi Hutter Epstein, MD is the writer in residence of Yale School of Medicine and author of Aroused: The History of Hormones and How They Control Just About Everything.
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