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2 April 2020

How do coronavirus tests work?

In the UK, a lack of testing has left us struggling to identify active cases of Covid-19. Developing a way to identify those who have already had the disease will be critical to fighting back.

By Michael Barrett

These are testing times. But in the UK we are not testing enough. Covid-19 is now ravaging the country (the death toll is 2,352, at the time of writing). Through January and February, suspected cases arriving from countries already suffering from the epidemic were tested. Saliva or sputum was collected on swabs and sent to a lab where the virus’s genetic material, ribonucleic acid (RNA), was converted into deoxyribonucleic acid (DNA) and then detected using a process we call the polymerase chain reaction, or PCR. 

The Word Health Organisation recommends testing widely and South Korea, which implemented the most comprehensive screening system globally, is showing the benefits of testing as its infection rates decline. In the UK, a slow response has created a dangerous situation where there is both a lack of test kits and delays in testing itself – every positive result in the country needs to be confirmed in London. The government hopes to rectify this by ramping up testing, but the damage has already been done.

The PCR test measures the virus only in active cases. As more and more people are infected – many of whom will have mild symptoms or no symptoms at all – it is critical that we develop new tests to determine who has had the virus and recovered. 

Infection triggers an immune response that, other than in fatal incidences, cures the disease and blocks further Covid-19 incursions. This enables those with immunity to be identified because they have specific antibodies to the virus. Tests for these antibodies are being developed by a range of companies and being validated by researchers at the University of Oxford; getting them into our communities en masse will be a major advance. The first such tests have already appeared in China, but their quality has been questionable. The challenge will be to get reliable and accredited tests distributed across the country.

Antibody tests work like a pregnancy test. The blood or sputum of a recently infected person will contain the antibodies they have developed to fight the disease, which can be detected by a series of reagents, either in a machine that allows multiple simultaneous tests or on specialist filter paper – where a coloured line emerges to indicate a positive result. Since those previously infected shouldn’t be vulnerable to reinfection, knowing whether they have had Covid-19 or not will enable a decision on whether they can rejoin wider society.  

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How are these antibodies made? Human existence depends upon our immune system recognising and killing microbes that constantly enter our bodies through the air we breathe, the food we eat, abrasions in our skin, and in many other ways. Our bodies fight most germs immediately through mechanisms that have evolved over millennia precisely to destroy such microbes. But microorganisms can evolve and develop ways to bypass these first-line defences, causing disease.

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For these pathogens, our bodies mount a sophisticated adaptive immune response. It takes around seven days for our immune system to develop a robust antibody to a microbe it hasn’t seen before. Our bodies will first undergo a series of intricate checks and balances to ensure the immune system doesn’t attack its own cells, and to verify the identity of a foreign invader. They then create specific antibodies, ingeniously crafted to recognise the particular parts of the pathogen, called antigens. Viruses are also detected by other cells, called T lymphocytes, that scan cellular surfaces for signs of intruders. This all takes time. But eventually we unleash the antibodies that specifically bind to and neutralise the pathogen. These antibodies attract further cells, called phagocytes, that engulf antibody-coated microbes and obliterate them. 

Antibodies will remain in circulation in the body even after the pathogen has been killed. A stock of antibody-producing B lymphocytes is also maintained, ready to start making the antibody in large quantities immediately, without the delay phase, should the same microbe reinvade later. Vaccines work by triggering these immune responses without exposing us to the infectious agent itself. Instead, they use key selected parts of an agent (antigens), or inactivated versions of the whole pathogen. 

In addition, antibodies from people who have recovered can be harvested and injected, as anti-serum, into infected recipients, offering some protection while their own immune system goes through the slow process of making its own response. 

The University of Glasgow, where I work on treating microbial diseases, has responded quickly to Covid-19. Face-to-face teaching was halted weeks ago, and tuition has all moved online. Summer exams will be performed remotely, if at all, with students writing essays at home and uploading their work for us to mark.   

But at the Centre for Virus Research, part of the university’s Medical Research Council, the work continues, and now focuses on Covid-19. Thousands of virus samples or isolates in Scotland are being sequenced to understand the pattern of spread and monitor any changes that could indicate mutated forms of the virus. The centre is also trying to develop a vaccine and novel drugs. 

Elsewhere, across the UK, research groups with their own PCR machines are putting their equipment to national use, as new diagnostic centres emerge to increase our ability to identify infected people. Lab workers are volunteering in droves to operate these machines and support the NHS in any way they can. 

I am of a generation for whom Dunkirk was considered the foundation of our national resilience. In the summer of 1940 a fleet of ordinary people with boats evacuated the British army from France, allowing it to fight another day. Today, we need everyone to support those in our NHS working around the clock to save us.