13th April 2020 – One of the Keys to End Lockdown is Reliable Antibody Mass Testing
A Blog by Dr David J Flavell PhD FRCPath & Dr Sopsamorn (Bee) Flavell BSc PhD
Scientific Directors of Leukaemia Busters
13th April 2020
Testing Times
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Why are there two completely different coronavirus tests and what are they for?
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What have been the problems that have delayed the development of an antibody test?
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A reliable antibody test is the key to unlocking the lockdown.
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The schedule of lockdown reversals will be determined by antibody testing.
Today, my biomedical scientist wife Bee and I are presenting this blog jointly because it’s on a vitally important subject, highly relevant to COVID-19 antibody testing and it’s one that we’ve worked on together, in a different context, for over three decades.
What we want to focus on is something that we’re hearing a lot about at the daily No 10 briefing sessions and generally in the news each day but for which there are still unclear answers being provided. It is the topic of testing patients, NHS staff and the wider public for the coronavirus that causes COVID-19.
It’s important because it is ultimately the key to unlocking the lockdown in a controlled and phased way as we are able to identify those individuals who can be released back into the community safely.
As research immunologists we have personally designed, developed and implemented many different types of “antibody test” (the most important of which is known in the trade as ELISA standing for Enzyme –Linked Immunosorbent Assay) and whilst these types of tests can be temperamental to get to work reliably there is always a solution to fix this.
Our understanding of this leaves us feeling exasperated at the length of time it is taking the UK authorities to get something in place right now.
The antibody test is so important because it is this test that will be key to establishing who has had COVID-19 infection and those who have not.
This information would then allow the release individuals who have had a previous infection back to a normal life secure in the knowledge that they are likely to be immune from further infection and crucially are not likely to further spread the disease to others (see my blog “Immunity & Vaccination” from the 10th April).
Firstly though, let us say something about the two different types of test that you’re hearing so much about and help clarify what they do and dispel some of the confusion there might be about these, what they actually detect and to what purpose.
Why are there two completely different coronavirus tests and what are they for?
There are two types of test for COVID-19, each of which tells us something completely different about the virus and infection. These are:-
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The Genomic Test (wrongly called the “Antigen” test)
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The Antibody Test
1. The Genomic Test (wrongly called the “Antigen” Test)
The Genomic test (that has been wrongly called the “Antigen” Test) Detects for the presence of the Viruses Genetic Material and NOT an Antigen.
The genomic test actually detects tiny amounts of the viruses genetic material in throat and nasal swabs from individuals tested. There are two main laboratory methods to detect this, RT-PCR that stands for real-time Reverse Transcriptase-Polymerase Chain Reaction that is widely used and at the moment the less widely used RT-LAMP method (standing for real-time Reverse Transcriptase-Loop-mediated Isothermal Amplification). The difference between the two methods is speed, with RT-PCR taking several hours to complete in contrast to commonly less than an hour for the RT-LAMP method which is also simpler to perform.
These tests therefore do not detect a viral antigen as government ministers, advisers and the media have been persistently and wrongly telling us for reasons that are not clear to us.
The key message to understand is that the genomic test detects whether there is “active” virus present in throat and/or nasal swabs from an individual, a sign that the person is actually infected and therefore infectious to others (whether symptomatic or not) at the time of testing.
When a person recovers from the infection after mounting an immune response against the virus the genomic test should in theory become negative as the patient clears the virus from their body.
However, a cautionary note here, studies coming out of China and elsewhere indicate that not everyone who recovers from COVID-19 becomes negative by the genomic test meaning that they may have become asymptomatic carriers and are therefore potentially still infectious to others (see the blog “Carriers” from the 5th April).
The significance of this is uncertain, the virus is so new that currently there’s insufficient information about this, a situation that will change as more testing is carried out and as time goes by more data become available.
2. The Antibody Test
A Reliable Antibody Test Would Allow the Lockdown to be Safely Unlocked in Stages
As its name suggests the antibody test detect antibodies against proteins on the surface of the virus called antigens in the blood of individuals. This tells us whether that individual has previously had the infection. As described in yesterday’s blog “COVID-19 Immunity: Kill or Cure?” the appearance of antibodies in the blood usually takes between 2 – 4 weeks after the initial infection and the point in time at which they appear is termed seroconversion and is assumed to be synonymous with the development of immunity.
Seroconversion occurs in two distinct phases the first that occurs usually around 2 weeks following infection is the production of a type of antibody called Immunoglobulin M (IgM) followed a week or two later by Immunoglobulin G (IgG) antibodies. Another type of antibody called Immunoglubulin A (IgA) is also important and appears around the same time but in the mucus lined surfaces of the lung and gut where they provide immunity and protection.
IgM antibody appears firstly as the initial defender followed by IgG and IgA which are much better in our defence because they attach much more strongly to the antigen on the invading virus and deliver a bigger punch. Such immunity is a wonderfully balanced system that operates every second of every day of our lives and of which we are completely unaware; how good is that?
Technical Difficulties with an Antibody Test are Surmountable
The ELISA test is one of the laboratory workhorses used by immunologists and other biomedical scientists to detect a whole range of substances in blood and other biological fluids and which we have used extensively in our leukaemia research work.
What is the problem?
The problems that have arisen in developing a truly reliable antibody test, that is, one that reports very few, or preferably no “false positive” or “false negative” results seem to be related to the nature of the viral antigen called the “spike” protein on the surface of the coronavirus which is comprised not just of one but of three separate but identical proteins that cluster together.
It is the spike protein that makes the COVID-19 coronavirus so highly infectious (see blog “What Makes COVID-19 So Very Contagious” 8th April). It is the unusual structure of the viruses spike protein that introduces some technical difficulties for the development of a truly reliable ELISA antibody test that we won’t go into detail about here other than to say that these problems are almost certainly surmountable.
We have faced similar problems with other antibody ELISA tests used in our own leukaemia research work but have always succeeded in overcoming these with a bit of lateral thinking. As we write scientists like us are now busily working on this problem and we’ve no doubt that this issue will be resolved very soon.
The big question then will be the availability of the appropriate amounts of highly specialised reagents and appropriate laboratory facilities for the test and precise protocols to ensure that each and every laboratory is conducting the test in exactly the same way for consistency and reliability.
A reliable and efficient antibody test that can be applied to mass screening of the population will help release from lock down those individuals who have had COVID-19 (whether they realise it or not) and who test positive for protective antibodies to return to normal life.
This would facilitate a staged exit strategy from the current lock down situation, something every one of us wishes for fervently.
Our own Simon Flavell Leukaemia Research Lab at Southampton General Hospital and some of the lab equipment we possess will be pressed into use for antibody testing for COVID-19 in the near future. Leukaemia Busters are pleased to help in whatever way it can to help defeat the COVID-19 problem so that we can all get back to normal lives as quickly and as safely as possible.
Important Lessons Learned……… We Hope
In the end it will be the judicious use of both RT-PCR and Antibody tests used together to screen the general population that will reveal the real picture and the true extent of infection rates, recoveries and immunity in the general population.
The RT-PCR test used on a wider scale than up until now to determine who is infected should lead to strict quarantine of these individuals who test positive followed up by contact tracing so as to isolate these individuals. This is exactly the reason why Germany and South Korea have kept their rates low, the simple tried and tested method of test, identify, contact trace and quarantine as recommended by the WHO but sadly not implemented in the UK, US and some other European countries that have also done relatively badly.
It’s too late now the virus is out there in the community and resultantly the only option to bring things back under control at this late stage in the game is the enforced lockdown of the whole population as we are now experiencing while the deadly game plays out over the coming weeks, understanding that those who are dying now are those who were infected 3 or more weeks ago before full lockdown was implemented.
The serious lesson to be learned from this is, as the WHO recommended in the first place, test, test, test, quarantine and contact trace to contain and keep the lid on spread.
Let’s hope that our politicians and those come after them in years to come will remember this lesson well for all our sakes.
