“Only a minority of people in Sweden have antibodies, so they can’t have herd immunity!”
That is the most common argument I’ve been hearing for why Sweden can’t have achieved herd immunity. This is in spite of the fact that the rates of hospitalizations and deaths have dropped continuously since the peak in April, and are now stable at basement levels.
The argument is also made in spite of the fact that the most recent currently available antibody data (showing that 19% in parts of Stockholm had antibodies and 7% in Sweden as a whole had antibodies) is three months old or older. And in terms of covid spread, three months is an eternity.
A study that was carried out in Japan over the summer, looking at the prevalence of antibodies among asymptomatic workers at a number of different locations around Tokyo, found that antibody levels rose from 6% to 47% over the course of the three summer months.
What conclusion can we draw? It is perfectly possible that 50% of Sweden’s population have antibodies by now, which negates the whole premise of the “only a minority have antibodies” argument. We’ll know whether that is true or not when newer antibody data becomes available from the Swedish public health authority later this year.
Apart from that, there are a few reasons why herd immunity might be achieved with only a minority of the population having antibodies, both epidemiological (to do with how the infection spreads in a population), and immunological (to do with how the immune system works).
In the rest of this article I will focus on the immunological reasons why herd immunity is possible when only a minority have antibodies. I have been receiving a lot of e-mails lately asking me about specifics of how the immune system works, so I thought it would be useful to discuss the topic in some detail. The following is a crash course in the workings of the immune system, which should help you to understand the current discussions happening in society about T-cells, antibodies, herd immunity, and whether reported cases of re-infection are real or not.
The immune system consists of two fundamental parts: the innate immune system and the adaptive immune system. The innate immune system is the first part to become activated when the body encounters a new pathogen, and it consists of four parts.
The first part is physical and chemical barriers like skin, phlegm, and stomach acid, that serve to make it harder for a pathogen to get further in to the body.
The second part is immune cells that specialize in hunting down and destroying foreign invaders. These include macrophages (literally “big eaters”), which eat or wall off anything foreign that they come across, and neutrophils, which destroy bacteria.
The third part of the innate immune system is proteins, produced by the liver, that interfere with the functioning of pathogens. The most important example is the complement system, which consists of a sequence of different proteins that bind to and disable pathogens. This is the reason people with liver failure are so prone to having severe infections – they no longer have these essential proteins floating around in their bodies.
The fourth part is a collection of internal mechanisms that all cells in the body have to detect when they have been invaded, and which causes them to activate internal defences and to warn neighbouring cells that there is an infection going on. Interferon is one such signaling molecule that is released by cells when they realize that they have been invaded by viruses. It causes the infected cell to lock itself down, making it much harder for viruses to replicate inside it.
The cells, proteins, and internal mechanisms of the innate immune system are all activated in the same basic way. They recognize conserved features that are common among pathogens. An example might be a molecule called lipopolysaccharide, which is common on the surfaces of many bacteria. Another example is double-stranded RNA, which does not exist naturally in the human body, and if it is present inside a cell it is a sign that the cell has been invaded by a virus.
Since the innate immune system is always present and always active, it can react quickly. But since it needs to be able to react to many different types of pathogen (bacteria, viruses, parasites), it is not particularly effective at dealing with any single one. It is like a swiss army knife – it does lots of different jobs, but none of them extremely well. That is where the adaptive immune system comes in.
The adaptive immune system consists of two main parts, T-cells and B-cells. B-cells make antibodies, which are proteins that can bind to pathogens and interfere with them in some way. Antibodies are similar to complement in the sense that they bind to and incapacitate pathogens, but whereas complement is always present and recognizes conserved features shared by many pathogens, antibodies are much more specific, and only appear after the body has encountered a new pathogen for the first time.
T-cells are the other part of the adaptive immune system. They can be further subdivided in to several specific types. The two main ones are T-helper cells (also known as CD4+ T-cells) and T-killer cells (also known as CD8+ T-cells).
T-helper cells are the “brain” of the adaptive immune system. They regulate the function of the other parts. Both B-cells and T-killer cells can only become fully activated after T-helper cells have been activated. That is why everyone who has antibodies by definition also has T-cells. T-helper cells are needed in order to activate B-cells.
The fact that T-helper cells are so central to the adaptive immune system is the reason HIV is such a deadly disease. The HIV virus specifically targets T-helper cells, and kills them. Without T-helper cells, the rest of the adaptive immune system cannot become activated, and so the person becomes highly susceptible to other infections. It’s not the HIV itself that kills people, it’s the fact that the immune system becomes too crippled to deal with other infections.
T-killer cells are quite different in function from T-helper cells. They are specifically designed to stop viral infections. Once they have become activated, they search out cells that have become infected by a virus and tell those cells to commit suicide. This prevents the virus-infected cells from releasing more viruses in to the body, and stops the infection in its tracks.
That is why T-killer cells are actually more central to the defence against viruses than antibodies are. T-killer cells keep viruses trapped inside infected cells, which prevents them from spreading and infecting other cells. Antibodies can only attack virus particles that are floating around outside cells – they can bind to and inactivate these virus particles, but they are only really keeping the problem at bay temporarily, because they cannot do anything about the virus particles that are multiplying inside cells. Antibodies are big molecules and have no way of crossing the cell membrane and entering cells. They always only exist outside cells. That is why antibodies are most effective at dealing with big pathogens that always exist outside cells, like most bacteria and parasites.
I mentioned before that B-cells produce antibodies. There are actually several different types of antibodies. When B-cells are first activated, they produce IgM. IgM are short lasting antibodies, generally present in the body for only a month or two at most, and they are not very specific. After a few weeks, the B-cells will usually do something known as “class switching”, where they will stop producing IgM antibodies and instead start producing other types of antibodies that are more specific. These new antibodies are generally much more long lasting than IgM.
There are four types of antibodies that can be produced after class switching. The most common antibody type is IgG, which is also the type most commonly measured in clinical antibody tests. IgG is found throughout the body.
Another important type when it comes to covid-19 is IgA, which is found primarily in areas where the body is in direct contact with the outside world, such as the lining of the respiratory tract and the gut (technically, the contents of the gut are outside the body – weird, right?). The reason IgA is important with regards to covid is that covid is a respiratory virus that is found primarily in the respiratory tract. The main difference between IgG and IgA is that IgA is hardier than IgG. It is designed to exist in harsh environments, like the respiratory tract and gut, where IgG would quickly be degraded.
Why am I talking about IgA? Because a recent study from Switzerland found that 15-20% of people who didn’t have IgG antibodies to covid-19 in their blood stream did have IgA in their respiratory tract. The reason this is important is because most antibody tests only look at IgG in the blood stream, which means that a significant number of people with antibodies to covid will be missed by standard antibody tests.
While the innate immune system is like a swiss army knife, the adaptive immune system is more like a very specific type of screw driver. It only does one job, but it does it very well. The adaptive immune system takes time to wake up the first time the body encounters a new pathogen, but the next time it encounters the same pathogen it reacts much more quickly, thanks to “immune memory”.
When the adaptive immune system is activated, some of the T-cells and B-cells will become memory cells. They will bide their time in the body in a state of dormancy, and the next time the body encounters the pathogen, they will quickly become activated and start mass producing clones of themselves. This usually results in the infection being dealt with before the rest of the body even realizes it has become infected.
What does this mean? That having immunity to an infection doesn’t prevent re-infection, as some people seem to think based on media reports of people having a second covid infection in spite of not having any symptoms. It just means that when re-infection happens, the adaptive immune system wakes up so quickly that the infection is dealt with before the rest of the body realizes what has happened. That is what immunity means, that the body reacts so quickly that the pathogen doesn’t have time to do damage, not that the body can’t be reinfected.
One thing to note about immune memory is that memory B-cells are dormant. This means that they are not actively producing any antibodies. So if you just look for antibodies in the bloodstream, you won’t know whether there are memory B-cells present in the body or not. What I’m getting at with this is that just because someone doesn’t have measurable antibodies any more after an infection, doesn’t mean that all the B-cells have disappeared, and doesn’t mean that the person no longer has B-cell based immunity.
A final thing to note is that T-killer cells and B-cells are activated along separate pathways (although both require T-helper cells to be activated). So it is perfectly possible for an infection to result only in T-killer cell activation, and also for an infection to only result in B-cell activation. Either pathway can result in immunity to viral infection. The more severe a viral infection is, the greater the likelihood that both pathways will be activated.
This has been shown clearly by a Swedish study that I wrote an article about a while back. In that study, more serious illness was correlated with a greater likelihood of developing both antibodies and T-cells. However there was a significant number of people who had T-cells specific for covid-19 but who didn’t develop antibodies. Those people likely have immunity to covid-19, but won’t be visible in an antibody test.
I hope this helps people understand the discussions currently going on about T-cells, antibodies, herd immunity, and whether or not people can be reinfected with covid-19, and also helps people to understand why it is perfectly possible to become infected with covid, and develop immunity, without ever developing measureable IgG-antibodies. I hope it also explains why it is perfectly possible to still have functioning immunity even if the antibodies that can be measured in the blood stream disappear after a few months.
You might also be interested in my article about why I think Sweden now has herd immunity, or my article about whether you should take fever lowering drugs when you’re sick. If you haven’t already done so, I would strongly urge you to read my guide to scientific method in medical and health science.