A “self-isolated” Prime Minister Boris Johnson addressed the British nation on April Fools’ Day 2020. Speaking from Number 10 Downing Street, he promised-somewhat inelegantly- to “ramp up” testing for Covid-19 in the UK, thereby “unlocking the puzzle” of coronavirus infection. This announcement confirmed a significant shift in the government’s policy, already drifting for some time, and more in keeping with the WHO’s oft-repeated advice to “test, test, test”.
The government’s initial coronavirus strategy can be likened to a policy of benign neglect. The theory was that the deliberate infection of a large proportion of the UK population would surreptitiously lead to “herd immunity” and thus control further spread of disease. Community testing was withdrawn and tests were limited to those seriously ill and admitted to hospital with probable Covid-19 infection. People with milder symptoms likely to be caused by Covid-19 were advised to self-isolate at home for up to 14 days, without ever finding out whether they were infected or not. It was accepted that a number of older people would inevitably die, while most could be protected through enforced isolation in their own homes for a forty-day period.
Normally, during a pandemic, diagnostic testing is an important public health measure that is used to quantify the extent of infection within the community. Surveillance testing provides information about the prevalence of infection, the proportion of asymptomatic carriers, the case mortality rate (the likelihood of death following infection), and rates of transmission (infectivity). This information can be used to track and thus effectively control the disease outbreak being studied. However, because of a lack of widespread testing, figures about the prevalence of Covid-19 infection in the UK are at best guesstimates. Furthermore, large numbers of healthcare workers have gone into self-isolation, not knowing whether they have been infected with Covid-19 or not. In addition, those healthcare workers still at work often do not know whether they have already acquired some immunity to Covid-19, thereby ensuring their safety in the workplace. These concerns have led to renewed calls for increased testing for coronavirus in the UK, focusing initially on healthcare workers.
Three types of coronavirus tests are currently available. The definitive diagnostic test is based on detecting the unique genetic sequence of Covid-19, using a Real-Time Reverse Transcriptase Polymerase Chain Reaction (PCR). A portion of the virus’s RNA is first transcribed into complementary DNA by reverse transcriptase, an enzyme. This DNA is then amplified by a second enzyme, a DNA polymerase, in a process that can be likened to making multiple photocopies, facilitating confirmatory analysis. PCR testing is performed on respiratory secretions, obtained by nasal and throat swabs, or sputum when available. It takes about 4 to 6 hours for a result to be obtained. In the UK, PCR tests are mostly performed in accredited laboratories within the NHS, leading to a time-lag between the completion of the test and the availability of the test result.
Newer tests are based on the identification of viral proteins, either the viral antigen itself or human antibodies produced in response to this antigen. These tests are performed on finger-prick blood samples. Results can be obtained within 15 minutes, making them more suitable for community screening, including at home and in airports.
Viral antigen can be detected by the LAMP method, which stands for “loop mediated isothermal amplification”. Another method, based on a gene-editing technique known as CRISPR (Clustered Regulatory Interspaced Short Palindromic Repeats), is also being developed.
Antibody tests (serological tests) are based on the detection of proteins known as immunoglobulins that are produced by the human body in response to viral protein. Typically, an initial surge of IgM antibodies is soon followed by the production of IgG antibodies. IgM antibodies eventually disappear, while IgG antibodies persist. IgM antibodies in isolation indicate the earlier stages of an infection. When IgM and IgG antibodies coexist, it means that recovery is underway, while IgG antibodies in isolation confirm full recovery. Antibody testing can thus be used to confirm exposure to, as well as recovery from, Covid-19 infection. Timing is all-important, as it probably takes the body at least 28 days after infection to mount an adequate antibody response. The detection of antibodies does not automatically imply protection against further exposure to Covid-19. This is because the ability to mount a protective immune response can depend on the actual level (titre) of circulating antibodies. The greater the level of antibodies, the higher the level of protection.
Laboratory testing for coronavirus infection is in its infancy. Already, the validity of many newer tests is being questioned. These tests are being developed in both academic institutions as well as private laboratories throughout the world, without any centralised validation. In the absence of any “gold standard” test, the mere fact that a test has been performed may actually mean very little. It is important that users can be assured of the accuracy of testing before tests are made widely available. The oversight of such bodies as the WHO, PHE and the US FDA is important in this respect. The validity of tests, and the correct interpretation of test results, must not be overlooked in a frenzy of testing that is mainly guided by arbitrary targets for numbers tested.
Ashis Banerjee (retired consultant in emergency medicine)