Covid-19: is long term immunity possible?

The immune response to SARS-CoV-2 infection is complex...

In order to eliminate the invading virus, many different immune cells are activated and then multiply rapidly. But can these activated cells fight off future infections? In other words, do people that recover from COVID-19 have long term immunity?

A key component of the immune response to any virus is the production of antibodies. When the immune system encounters a virus, antibodies are produced rapidly by B cells. We now know that most people infected with SARS-CoV-2 produce antibodies within 10 days of infection. This means that testing for antibodies to COVID-19 is a good way to tell whether a person has previously been infected with the coronavirus.

But what we cannot say yet is if these antibodies will protect someone from re-infection at a later date. This is for two reasons: first, we do not know how long these antibodies persist in the bloodstream; second, which “kind” of antibody provides the best protection is also unclear. This is because antibodies are organised into different classes that are preferentially produced at different sites in the body. These include IgG antibodies, which circulate in the blood, and IgA antibodies that are present in secretions like tears and digestive juices. Different infections (and vaccination strategies) may produce relatively more of one antibody class than another, so it is important to understand which provide the best protection. Also, different individuals may make relatively more antibodies against some parts of the virus than others, which can also affect the level of protection they afford.

We can make sensible estimates for how long COVID-19 specific antibodies may last by looking at other coronavirus infections. For SARS-CoV-1, which circulated in 2002-2003 and caused the first SARS coronavirus outbreak, it has been shown that antibody levels fall within 3 years of infection. For volunteers experimentally infected with the human coronavirus HCoV-299E, which is one cause of the common cold, virus-specific antibodies were gone within a year. Unfortunately, this suggests that protective COVID-19 antibodies might not be very long-lived.

As to which type of antibody is most effective, each person seems to make antibodies against many different parts of the SARS-CoV-2 and in a wide range of quantities or ‘titres’.

Antibodies targeting the virus spike protein have been the focus of lots of research attention. The spike protein is needed for entry into cells, hence antibody binding to the spike should stop virus invasion and replication. Despite this, the spike protein is large and some antibodies can bind to parts of the spike that don’t affect its ability to penetrate a cell. Standard assays that simply measure binding to viral proteins cannot always differentiate between these antibody types, so we need to beware of this.

To get around this issue, advanced tests are often used to measure the ability of antibodies to actually prevent viruses from infecting cells. These tests are known as ‘neutralisation assays’. However, such tests require live virus (either SARS-CoV-2 or a modified version), so are much more challenging and potentially risky to perform. New data suggest that many COVID-19 patients do not make high levels of neutralising antibodies, but the significance of this is currently uncertain.

Scientists are therefore now working to determine the full breadth of antibody responses to SARS-CoV-2, and establish new tests that can accurately measure all these different types of antibodies. There are 29 different proteins in SARS-CoV-2, and it has been shown that in addition to the spike, humans make measurable antibody responses to at least 10 of these proteins. It’s not known if these non-spike antibodies are relevant, but it is likely they have some role.

Finally, it is important to remember that the immune response to COVID-19 is not all about antibodies. Many other cells and proteins are involved in the immune response to any virus. Particular focus is on the role of T cells; these immune cells are able to kill virally-infected cells in a highly-specific manner. Testing for T cells is more difficult that testing for antibodies, but research is aiming to examine every possible angle.

As the COVID-19 pandemic progresses, continued study of COVID-19 immune responses over time, coupled with surveillance for which individuals get repeated infections, will be critical.

With the current pace of research, it looks promising that we will soon be able to generate a clearer picture as to what the ‘ideal’ immune response looks like. This will be invaluable for both predicting who is susceptible to a second infection, and also for vaccine development.  If we know the optimal immune response to COVID-19, we can strive for vaccines that recreate this protection.