COVID-19, A testing opportunity

COVID-19, A testing opportunity

COVID-19, A testing opportunity

The issue in tracking the spread of the SARS-CoV-2 virus throughout the population is that the two tests being suggested are, an untested antibody test, providing best results 21-28 days after showing symptoms of the COVID-19 disease, or a manpower, technology, reagent and skills intensive PCR test looking for active virus a period of time post infection.

A percentage of the population remains asymptomatic as they carry the virus but can transmit it.

The PCR tests are and will always be resource limited. Those infected with the SARS-CoV-2 virus may be infective for a period before the PCR tests will identify active infection.  The test is only accurate at the moment of time the swab was taken and there is nothing to stop someone not infected at the time of test being subsequently infected at any time after the test.  The reagents needed for the test are in a short supply across the globe and testing facilities are becoming overwhelmed.

Current “mass” screening capability used in several countries uses thermal cameras looking for people with elevated temperatures. However, it will not identify asymptomatic carriers and only detects one symptomatic indicator.

What is needed are a series of complimentary tests able to identify an infection and immune system activation as early as possible so that infected persons can isolate as early as possible to reduce cross infection risk, once isolated then individuals can be tested for specific viruses such as SAR-CoV-2 and then for antibodies.

Tests should be simple and cost effective enough to allow individuals to be tested as often as is deemed necessary. For example, healthcare staff on arrival at work and on leaving work each day.  There is currently insufficient PCR capability to do this and it is unlikely there ever will be. PCR tests are relatively expensive.

Research post the original SARS epidemic believed to have emerged in 2002 identified the utility of a viral infection marker produced by the body as part of a stimulated immune response.  The marker is called Neopterin.  There are numerous scientific papers outlining the utility of this chemical marker including:

Serum neopterin for early assessment of severity of severe acute respiratory syndrome.

The emerging utility of neopterin?

Neopterin in Diagnosis and Monitoring of Infectious Diseases

The immune system being activated and releasing Neopterin is not specific to SARS-CoV-2, however it is an early warning system that something is going on; currently there is no test that does this.

Professor Colin Self, an Emeritus professor with Newcastle University and recognised leading testing scientist as developed a simple revolutionary test that could be used for that early warning capability utilising the detection of Neopterin in saliva.

The base technology used for the test has been developed over many years of research under Framework 7 and Horizon 2020 funded research projects. It can be used to detect any small molecule where a specific antibody for that molecule can be found. It is simple positive read out test, that gives results in less than 2 minutes.

As an antibody is specific to a particular chemical structure, this methodology is extremely accurate. Professor Self has a very pure cell line producing antibodies to Neopterin. The use of saliva, the positive read out if neopterin is present and the speed of testing allows self-testing and self-reading of the result.  Each test if produced in volume batches, only costs a few pounds.

Imagine everyone being able to test themselves several times a day and if positive the more expensive PCR tests can be used in a targeted way to track SARS-CoV-2, if negative you know you do not have an immune stimulating infection.

Professor Self has told me that whilst his test is in storage as his research grants have finished, he has identified a qualified team with availability, facilities to produce a production standard test in approximately 6 weeks and then the manufacturing process to produce 10’s of thousands of test strips per day or potentially significantly more would be easily achievable.  His tests don’t need special reagents, he can grow volumes of the relevant antibodies quickly, large numbers of test strips can be manufactured easily.

A video of the test being used in real time is below:

 

The presence of small molecular weight analyte (Neopterin) gives rise to a positive line appearing out of a clear white background. Intuitively, the more line is seen the more Neopterin is present.

The cassette dipstick on the left receives neopterin-free buffer, whereas the cassette dipstick on the right receives buffer containing the small molecular weight analyte.

During the, real-time run, both cassette dipsticks display a positive control line towards the top of the window to show the devices have been used correctly. Only the cassette receiving a positive sample shows a positive test line, towards the bottom of the window.

This occurs very quickly. The fact that the positive sample is indeed positive can be seen by eye within a matter of seconds, allowing immediate action to be taken if necessary. Further development of the sticks over two minutes, allows the control line to stabilise and a quantitative determination of the concentration of the analyte.

All Professor Self needs is help taking this ground-breaking test to production. It could enable better control of pandemic conditions.

 

COVID 19 test, but there are tests and tests!

COVID 19 test, but there are tests and tests!

COVID 19 test, but there are tests and tests!

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 some help from 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.

Related Article: https://www.providertech.com/covid-19-test-results-how-texting-makes-it-easy-for-patients-to-access-lab-results-from-epic/