The Crick’s George Kassiotis studies how our bodies respond to viral infections and in March he refocused his work to study SARS-CoV-2 and COVID-19. Here, he answers some of the key questions about antibody testing.
How do we test for antibodies?
There are lots of antibody tests that work in different ways. But they all have one thing in common – they detect the presence of antibodies that bind to proteins in the virus. The tests differ in which protein they’re examining, and how they detect the antibodies.
There are two main groups of tests – qualitative commercial tests are relatively quick, require less kit and just tell you whether the antibodies are present or not. Quantitative research tests tell you which specific antibodies are present and how much of them there is.
Why do we need to know how antibodies respond to SARS-CoV-2?
This particular coronavirus has a fatality rate of between 0.6% and 0.9%. That means that less than one in a hundred cases of COVID-19 result in death. In all the other cases, the immune system eventually fights off the disease.
This means that, if we understand how antibodies respond to SARS-CoV-2, it should be possible to use a vaccination to train our immune systems to provide better protection and consistently fight off the virus. Examining the antibodies present in people who have been infected helps us to build up a picture of the immune response and know what works.
Antibody tests can also help us monitor who has been infected with the virus - an important tool to map the spread of the virus and see how it has moved through the population.
When can we start to look for antibodies?
The amount of virus in your body is at its highest after around the first five days. After those initial few days, antibodies begin to be produced and the virus begins to drop off. As the amount of the virus – or ‘viral load’ – decreases, the antibodies will remain in the bloodstream for weeks or months. Antibodies hanging around in our bloodstream are part of what we call ‘immunological memory’, and in general we’re able to fight off the virus again as long as the antibodies are still around.
How long does immunological memory last for SARS-CoV-2?
We really don’t know at this stage. The virus simply hasn’t been around long enough for us to study it over a long period of time.
Some viruses are very memorable. For example, the measles vaccine will last almost your whole lifetime because the antibodies stay for decades. But other viruses – like the coronaviruses that cause common colds – are very forgettable and the immunological memory can fade after a few months.
SARS-CoV-1 (identified in 2003) was more severe than SARS-CoV-2 and seemed to result in immunity for around two years in most people, and up to 12 years in a few people. Our best estimates for the immunological memory period for SARS-CoV-2 are somewhere between SARS-CoV-1 and common cold coronaviruses.
The length of the immunological memory also depends on the severity of the infection. If you have more of the virus present in your body, you’ll produce more antibodies and the immunological memory will last longer.
If you have antibodies to SARS-CoV-2, does that mean you’ve been infected?
Generally yes, but not necessarily. SARS-CoV-2 is not the only coronavirus out there, and all of us will have been infected with seasonal coronaviruses and produced antibodies to them. In some of us, these antibodies can also bind to proteins from other coronaviruses and even SARS-CoV-2.
This has made developing antibody tests very difficult, as we have had to find ways to differentiate between antibodies to the different coronaviruses. So the answer is yes, as long as you’re using a sophisticated test that can tell the difference between the antibodies.
If you don’t have antibodies to SARS-CoV-2, does that mean you haven’t been infected?
As a rule, yes. There are a couple of exceptions, like people with immunodeficiency who won’t make antibodies. But generally everyone who has been infected with SARS-CoV-2 will produce antibodies. They might not make them immediately or keep them indefinitely, but they will make them.
If I get a positive antibody test result, am I immune?
This sounds simple, but it’s an incredibly complex question. Firstly, antibody tests don’t necessarily show immunity. Secondly, there are different ways to define ‘being immune’.
Antibodies appear while you are infected with the virus, and stay after you have cleared the infection. You might still have that first infection and get a positive result on antibody test, as the virus and the antibodies can exist side by side in your bloodstream. In that case, you could still be infectious.
Based on our best tests, we think the infection normally lasts for around two weeks. However, there are reported cases of the virus lingering on for months, despite the antibodies being present and the person not necessarily showing symptoms. A better question to ask would be…
If I have made antibodies and cleared the first infection, am I immune?
Most tests will tell you if you have produced antibodies, not how many antibodies you’ve produced and how good they are. These two factors are really important in immunity and you’re not necessarily getting the full picture without knowing the answers. But if we make the question even more specific…
I have made a sufficient amount of antibodies of the right type and I’ve cleared the first infection, am I immune?
This depends on what we mean by ‘being immune’. If you take immunity to mean ‘having complete protection against the virus’, then the answer is probably yes. But complete protection is not likely to last very long. However, partial immunity lasts a lot longer and is still very important. Partial immunity can slow the spread of the disease and reduce the severity of symptoms.
We still don’t know the outcome if you’re infected a second time, and what role your antibodies play, but all our expectations are that the second time you’re infected with SARS-CoV-2, the symptoms will be much milder and you’ll be able to clear the infection more quickly.
Find out more about our research on Covid-19 immunity and immunopathology – testing and mechanisms.