by Philip Ingram MBE
Some see a perceived lack of testing as the latest stick to beat the government up with the current COVID-19 crisis. The perception that is being left with the general public and with healthcare workers is that testing will provide some magic solution to the crisis. The reality is, being blunt, it won’t; being more accurate, each test has its strengths and weaknesses and no one test is the complete answer, they will only help our understanding of the spread of the infection and help keep us safer.
The current test, which is the one being scaled up, is an ‘antigen’ test. Antigens are molecules capable of stimulating an immune response in the body and that immune response is the start of the production of antibodies.
The antigen test requires a swab to be taken, usually from the back of the throat. That swab then needs to be sent to a laboratory where the antigen is scientifically amplified and compared with a reference to see if it is what they are looking for. This test, called the Polymerase Chain Reaction (PCR), often referred to as real-time PCR (rt-PCR), or the quantitative PCR (qPCR) test, requires trained laboratory technicians, specialist equipment and time for each test, as well as an administrative burden matching tests to results and informing individuals of results.
The current PCR test is an excellent technology but leaves a window as it misses some early cases, at times not detecting infection until a period post symptoms, even though the person can be highly infectious during that time. The test is also manpower and equipment limited, needing people to take samples, technicians and scientists to process and interpret the tests and staff to deliver the results.
Of course, a negative test one day does not mean the individual could not become infected the next day, and this is why it is essential the complimentary Antibody test is further developed and rolled out to identify who has had the infection.
This is a much simpler test using a sample of blood taken from a finger pin prick and it is then put into a device like a pregnancy test kit, but the chemistry on the test stick is designed to look for antibody. Antibodies (sometimes called immunoglobins (IgM and IgG)) are proteins produced by the body over the course of a week or two in response to an infection and are there to fight the infection. Each antibody is designed to recognise a specific part of the cause of the infection (the antigen), lock onto it and stop it replicating thereby fighting the infection.
With the antibody test, a solution is added, and the blood sample moves up the test paper stick, interacting with the chemistry on the stick and giving an indicator that the antibody is present. This will tell someone that they have had the COVID-19 disease in some form and only takes a few minutes to carry out. It does not indicate early infection or necessarily that an individual currently has the infection.
There are other tests currently being offered to the fight against COVID-19 that will complement the PCR antigen and the antibody test. This test is similar in its physical form to the antibody test, but the chemistry is very different. It detects a key very early marker of the activation of the immune system in the body produced from the very early stages of the infection. This happens as the infection enters the body and is active as the body produces certain ‘help’ molecules. A marker that has been identified, following a great deal of research activity into HIV and earlier SARS infections is called neopterin.
The neopterin test does not specifically identify that an infection is COVID-19, but it does detect that someone is suffering from an activation of their immune system and, as such can detect infection at a much earlier stage in the disease than any of the other tests. It is a very simple to use and understand lateral flow test (as a pregnancy test) and can be used and interpreted by health workers and the general public, requiring no specialist support. It is projected to be non-invasive by using only a small sample of saliva, with the test results showing a positive result with a red line in a few minutes only if the individual is suffering a current viral infection.
This new test is not yet part of the governments offering but would complement the other two allowing the resource and time-consuming PCR test to be used only on those who have a positive indication of a viral infection and, critically, detecting those that are too early in the course of infection to be detected by the PCR or antibody test. It could also be used much more frequently as part of a wider screening programme as it can be self-administered, self-interpreted and produces rapid results and allow more informed self isolation, thereby reducing cross infection, potentially dramatically.
What is important is that the strengths and limitations of each type of test are known and understood and that a range of complimentary tests are available to maximise the collection of results that will rapidly let the health system and public understand the risks.
This article was written by Philip Ingram MBE with the assistance of Professor Colin Self BSc, MB, BChir, PhD, DSc, FRSC, FRCPath who has developed the Neopterin test. Please use the contact us page if you want further details.