Antibody testing for Covid-19

07 July 2020

Interview with 

Chris Xu, Thermogenesis; Sara Lear and Anita Chandra, Addenbrooke's Hospital

BLOOD-TEST-SAMPLES

Blood samples being tested in a laboratory

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What about the question of whether you've had the infection in the past? This is where tests for antibodies come in. If there are antibodies against an infection in the blood, it shows that a person has been exposed to that infection previously. As immunologist Chris Xu puts it, antibodies are a bit like the footprints an animal leaves behind. And by identifying those footprints, you can tell what animals have been in the neighbourhood. At his company Thermogenesis, he's invented a test kit that people can use at home...

Chris Xu - The test is very simple. It's attacking humans' immune response against the virus. It takes one droplet of blood, and we can read the result in about two to three minutes. The test we believe to be more than 90% accurate.

Chris - But that still means that you're potentially getting it wrong 10% of the time, doesn't it?

Chris Xu - Yes. Each test has its limitations. There are many different factors that could be affecting the performance of a test, such as viral mutations. If the virus mutated things then certainly it will not be recognized by the antibody tests. Or also the blood chemistry might interfere with the performance of the test.

Chris Xu sent Chris Smith some samples of his test so that we could try it against another kind of antibody test, this time one that can be run in a laboratory to test large numbers of patients quickly and accurately. It’s been developed by immunologists at Addenbrooke’s Hospital in Cambridge.  Chris Smith went to see Drs Sara Lear and Anita Chandra and asked them to tell him how their test works, and to put Chris Xu's test to the test using Anita’s own antibodies! But first Anita answered this crucial question..

Anita - An antibody is a protein that circulates in the blood or can be in various tissues of the body and its job is to help fight various forms of infections be they bacteria, viruses or parasites. There are many different forms, what we call classes of antibodies, and there are lots of antibodies against different bugs. So you can have antibodies against coronavirus, mumps, measles.

Chris - Where do they come from?

Anita - We have white cells that circulate in the blood and are made in our bone marrow that have the capacity to produce what we call IgM antibodies. So these are the first type of antibodies that are our first line of defense and they have the capacity to recognise millions of different organisms. On the first exposure to, for example, a virus like coronavirus, we would make an IgM antibody. And then at a later stage, we would make a different type of antibody called IgG antibody.

Chris - Why make two different types?

Anita - The IgM is produced immediately. It has different effects to other cells of the immune system. The IgG comes along later - it circulates in the blood, has a long half life up to three weeks and it can cross the placenta. And it's the IgG antibodies that we measure when we look at vaccine responses, for example.

Chris - And Sara, if you make two different types of antibody at two different times, does that mean you could use that as the basis of a test for whether someone's got something right now or had something previously?

Sara - Yes. The IgM comes first. It's pretty quick. Within 24 hours, it starts being built up, peaks at about three days. And then the IgG kicks in after that. So if you do a test right at the beginning, you can measure the IgM and you can tell that's more likely to be an acute infection. And then if it's not an IgM, but an IgG, you can say, well, this has happened sometime in the past and it's not recent.

Chris - That's one of the things you've done here at Addenbrooke's, you've managed to make a test that actually looks for the antibodies against this new coronavirus. How does it work?

Sara - So all these tests work with the same principle that we need to get the bits of the virus that we're looking for, and we have to fix them somewhere and expose them to the antibody in the patient's blood. And then we have to be able to see that antibody protein complex. So in this case, we took the viral proteins and we stuck them onto tiny microbeads. And then we incubate that with the patient's serum, they stick together if the antibodies are there. Shine lights at it, and if you've got an antibody antigen complex there, then it will shine up and give you a light measurement.

Chris - And it glows only if the antibodies are stuck on?

Sara - Exactly.

Chris - And it works?

Sara - Yes! Yes, it does work.

Chris - Now I got you here under slightly false pretences Anita, because Sara let it slip that actually you're a positive control in all her experiments, because you have antibodies. You have without realising it had coronavirus infection. So will you be a guinea pig for us?

Anita - Yes. I'm very happy to be your guinea pig.

Chris - Okay. I understand you are the lab guinea pig anyway. This is a point of care test, which has been sent to me from a laboratory in America. And the way it works is that we need a sample of blood from your finger, and it will register whether you have antibodies of the IgG or IgM type. You need to use this alcohol soaked swab to make it all clean.

Anita - Thank you.

Chris - You're now going to take that green thing, which is sprung loaded, and you hold that against your finger and it's going to put a little tiny blade into the skin and we should make a hole in you and some blood should start to come out. Press that. Are you alive?

Anita - I'm still alive!

Chris - Use the little pipette I've got here and just suck that drop of blood up off your finger. Blimey there's a lot coming out. There's a nice dry swab. This is the actual test cartridge. It's about the length of your finger. And it's about the width of your finger as well, isn't it. And there is one end which is a well where you put the sample. And then there is this area about a centimetre long and about two or three millimetres wide. That's where we're going to see your result. So what you have to do is take about five drops of your blood. Yep. Using the pipette and just drop it where it says S for the sample.

Anita - Here?

Chris - Yup. So in goes the sample. Now we just have to leave it to cook.

Anita - Okay. Is this like a little pregnancy test?

Chris - Yes, it does give lines. Just like pregnancy tests. There's a C there, which is the control one, which says it has worked. And then there are two or one line will come up for antibodies on there. We'll put that to one side and we'll see in a minute what the result is. Sara, do we feel we understand how we respond to coronavirus infection?

Sara - So I think no has to be the answer to that one. There are some features of this virus that appear very different and that are unusual. The antibody test will help, I think, to pick up how many people in the environment have been exposed to it, but we need to do more work around the acute infection to see how it actually evolves.

Chris - Do we have any feeling Anita for once you've made a response, whether that lasts very long or does it disappear?

Anita - That's what we're still trying to ascertain in the labs at the moment. I think a lot of that data from China will be very important because they are now at least six months in and they will be able to look at the patients and their convalescent samples to see how long they have antibodies and whether they are protected.

Chris - Why should the antibody disappear though? It seems a bit strange that for some infections you have antibody and you have it for life. Whereas with this one we're uncertain as to whether it will hang around for any appreciable time. Why might that be the case?

Anita - Some of the other SARS-like viruses, they found that the antibodies only last for two years, I don't know why it's only two years in this SARS-virus, whereas for some patients like the influenza virus, there are patients who are over a hundred and who were exposed in 1918, and they still have evidence of antibodies to the influence of virus. So for that, I'll have to raise my hands and say, I don't know.

Chris - What might the implications for a vaccine be then Sara?

Sara - Vaccines work in two ways and the antibody response is only part of that. There's also a cellular response, which forms a really important part of how you clear viruses from the system.

Chris - Cause researchers in Sweden this week have said that there are people knocking around who don't have appreciable antibodies, but they are sure as hell immune to this new virus. How might that be then?

Sara - When your body comes across a new virus, T cells come along and they recognise those proteins exposed on the cell surface as being foreign and that can induce a cellular response, which means that the cell that's infected gets destroyed. And the cells will be able to recognise that combination again in the future and will then protect you for longer term.

Chris - So you can have low levels of antibody, but because you've got these T cells that recognise a virally infected cell, that's going to give you protection as well. So it's not just a one prong, it's a two pronged response.

Sara - Yes. And there are other cells and neutrophils when exposed to coronavirus, they produce these little nets that capture them and eat them. The immune system is very complicated, which is why it's very, very interesting to study.

Chris - Well, look, I think on that note, it's moment of truth time isn't it. Should we have a look and see? So here is your result, Anita, and I see one very strong red line against the control showing that the test has worked, but come on immunologist, is there anything else on that line, on the IgG?

Sara - Yes, I think there's a faint line on the IgG. It's very faint.

Chris - Okay. With the eye of faith, there might be a very faint line where the IgG antibodies are. Have you had it Sara?

Sara - I haven't had the test.

Chris - Because you share an office with this woman.

Sara - So I'm safe, right?

Chris - Not initially, not potentially.

Sara - I haven't done it because I haven't been ill.

Anita - Out of curiosity, you haven't checked?

Chris - You wanna, do you want to do a test?

Sara - I don't trust that!

Chris - I don't like your test. It's not as good as mine.

Sara - I haven't got around to it!

Chris - Should we make her do one of these?

Anita - I think we should!

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